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Purpose: Thyroid cancer incidence has increased in recent decades, and thyroid surgery is continuously evolving in response to demands for postoperative comfort and cosmesis. This study aimed to introduce a new surgical method for minimally invasive open bilateral total thyroidectomy (MI-BTT) using a unilateral 2.5-3.0 cm neck incision. Furthermore, we reported the surgical outcomes and postoperative quality of life (QoL) using a validated Korean translated Dermatology Life Quality Index (DLQI) questionnaire., Materials and Methods: We retrospectively evaluated 41 Asian patients who underwent MI-BTT for low-risk papillary thyroid cancer by a single surgeon from March 2019 to December 2021., Results: A total of 4 male and 37 female patients were included. The mean age and body mass index were 46.2±10.1 years and 23.3±3.3 kg/m², respectively. The average tumor size was 1.1±0.6 cm, and 36 patients (87.8%) had bilateral cancer. Twenty-three (56.1%) patients had occult central lymph node (CLN) metastasis in the final pathologic report, with the mean number of dissected CLNs being 7.2±6.5. Gross capsular extension was found in 6 patients (14.6%). Moreover, 28 patients (68.3%) received additional treatment after surgery with low or high doses of radioactive iodine. The average serum-stimulated thyroglobulin value identified during treatment was 1.57±2.30 ng/mL. The mean operation time was 78.0±13.9 minutes, and postoperative complications included transient hypocalcemia (36.6%), transient hoarseness (24.4%), and seroma (2.4%). The mean total DLQI score was 2.73±0.78, indicating a small effect on QoL., Conclusion: MI-BTT is a novel, safe, and feasible technique to improve patient satisfaction for surgical scars and QoL., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: The diffuse sclerosing variant (DSV) is among the aggressive variants of papillary thyroid carcinoma (PTC) and is more prevalent in pediatric patients than in adult patients. Few studies have assessed its characteristics owing to its low incidence. We aimed to evaluate the relationship between recurrence and age in the DSV of PTC., Methods: We retrospectively reviewed patients diagnosed with the DSV or conventional PTC (cPTC) after surgery at a medical center between May 1988 and January 2019. We compared the clinico-pathological characteristics and surgical outcomes of the DSV and cPTC groups and between adult and pediatric patients with DSV., Results: Among the 24,626 patients, 202 had the DSV, and 24,424 were diagnosed with cPTC. The recurrence rate was significantly higher in the DSV group than in the cPTC group. In the DSV group, the recurrence rate was significantly higher in the pediatric patient group than in the adult patient group. Moreover, the association between recurrence and age group showed different patterns between the DSV and cPTC groups with restricted cubic splines (RCS). While both RCS curves showed a U-shaped distribution, the RCS curve tended to be located within the younger age group., Conclusions: This study demonstrated that pediatric patients with DSV are at a greater risk for recurrence compared with adult patients; moreover, the pattern of recurrence risk according to age is different from that of cPTC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Koo, Bang, Kim, Kang, Jeong, Nam and Chung.)

With the progress of robotic transaxillary thyroid surgery (RTTS), the indications for this procedure have gradually expanded. This study presents the insights gained from performing 10,000 RTTS cases at a single institution, along with the expansion of indications over time. RTTS was performed on 10,000 patients using the da Vinci robot system between October 2007 and April 2023 at the Yonsei University Health System, Seoul, Korea. Among 10,000 patients, 9461 (94.0%) were diagnosed with thyroid cancer, whereas 539 (5.4%) had either a benign thyroid nodule or Graves' disease. Surgical procedures were performed using four-arm-based robots (da Vinci S, Si, or Xi) for 8408 cases (84.1%), with the remaining 1592 cases (15.9%) being performed using the da Vinci SP surgical robotic system. Notably, for 53 patients with nodules ≥ 5 cm, which were not included in the eligibility criteria of the previous study, RTTS was performed safely without significant complications. The most common postoperative complication was transient hypoparathyroidism (37.91%), and recurrence occurred in 100 patients with thyroid cancer (1.1%). In conclusion, RTTS appears safe and feasible from both surgical and oncological perspectives, and the spectrum of indications suitable for RTTS surgery is progressively expanding., (© 2024. The Author(s).)

Background: Fine-needle aspiration biopsy (FNAB) is a good diagnostic tool for thyroid nodules; however, its high false-negative rate for giant nodules remains controversial. Many clinicians recommend surgical resection for nodules >4 cm owing to an increased risk of malignancy and an increased false-negative rate. This study aimed to examine the feasibility of this approach and investigate the incidence of malignancy in thyroid nodules >4 cm without suspicious cytology based on medical records in our center., Methods: This was a retrospective analysis of 453 patients that underwent preoperative FNAB for nodules measuring >4 cm between January 2017 and August 2022 at Severance Hospital, Seoul., Results: Among the 453 patients, 140 nodules were benign and 119 were indeterminate. Among 259 patients, the final pathology results were divided into benign (149) and cancerous (110) groups, and the prevalence of malignancy was 38.9% in the benign group and 55.5% in the indeterminate group. Among the malignancies, follicular carcinoma and follicular variants of papillary carcinoma were observed in 83% of the cytologically benign group and 62.8% of the indeterminate group., Conclusion: Preoperative FNAB had high false-negative rates and low diagnostic accuracy in patients with thyroid nodules >4 cm without suspicious cytologic features; therefore, diagnostic surgery may be considered a treatment option., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kang, Kim, Lee, Kim, Lee, Kang, Lee, Jeong, Nam and Chung.)

Objectives: This study aimed to demonstrate the usefulness of single-port transaxillary robotic modified radical neck dissection (STAR-RND) for metastatic thyroid cancer, and its potential to make small and invisible surgical wounds possible compared to open modified radical neck dissection., Methods: Between January 2020 and July 2021, 30 thyroid cancer patients who underwent lateral neck dissection surgery with the da Vinci SP at Yonsei University Health System (Seoul, Korea) were studied., Results: All 30 patients, diagnosed with papillary thyroid cancer were women. The average operating time was 293.80 ± 36.58 (min), and the average postoperative hospital stay was 4.77 ± 0.57 (days). All patients were discharged after the expected number of hospitalization days without major complications., Conclusion: STAR-RND is technically feasible and safe with a short length of the incision. To our knowledge, this is the first report on the use of a single-port robotic system for modified radical neck dissection. LEVEL OF EVIDENCE BY USING 2011 OCEBM: 4 Laryngoscope, 133:709-714, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Locoregional recurrent thyroid cancer is commonly treated with re-do operation. This study aimed to investigate the feasibility of using robotic system for re-do operation in locoregional recurrent thyroid cancer. Sixty-five patients who underwent re-do robotic operation using trans-axillary approach for locoregional recurrent thyroid cancer from October 2007 to April 2021 at Yonsei University Hospital were analyzed. Completion total thyroidectomy (CTT) was performed in 26 cases, CTT and modified radical neck node dissection (mRND) in 16, and mRND in 23. Most of the re-do robotic operations were performed at site of previous incision. All patients were diagnosed with papillary thyroid carcinoma (PTC). CTT with central compartment neck dissection (CCND) took 117.6 ± 26.3 min, CTT with mRND 255.6 ± 38.6 min, and mRND, 211.7 ± 52.9 min. Transient hypocalcemia occurred in 17 (26.2%) patients and permanent hypocalcemia occurred in 3 (4.6%). There was one case of recurrent laryngeal nerve(RLN) injury. One patient was diagnosed with structural recurrence after re-do robotic operation. Median follow-up duration was 50.7 ± 37.1 months. Re-do robotic operation can be an alternative for patients who are diagnosed with locoregional recurrent thyroid cancer after thyroidectomy, with no increase in morbidity, similar oncologic outcomes, and superior cosmetic satisfaction., (© 2022. The Author(s).)

Background: This study aims to report the results of a pioneering clinical study using the single-port transaxillary robotic thyroidectomy (START) for 200 patients with thyroid tumor and to introduce our novel two-step retraction method., Methods: START was performed on consecutive 200 patients using the da Vinci Single-Port (SP) robot system from January 2019 to September 2020 at the Yonsei University Health System, Seoul, Korea. The novel two-step retraction technique, in which a 3.5 cm long incision is made along the natural skin crease, was used for the latter 164 patients. The surgical outcome and invasiveness of the SP two-step retraction method were analyzed., Results: Among the 200 cases who underwent START, 198 were female and 2 were male, with a mean age of 34.7 (range: 13-58 years). Thyroid lobectomy was performed for 177 patients and total thyroidectomy was performed for 23 patients. Ten patients had benign thyroid nodules, whereas the other 190 had thyroid malignancy. The mean body mass index (BMI) was 22.2 ± 3.7 kg/m 2 (range: 15.9-37.0 kg/m 2 ). All of the operations were performed successfully without any open conversions, and patients were discharged on postoperative day 3 or 4 without significant complication. The mean operative time for thyroid lobectomy with the two-step retraction method was 116.69 ± 23.23 min, which was similar to that in the conventional robotic skin flap method (115.33 ± 17.29 min). We could minimize the extent of the robotic skin flap dissection with the two-step retraction method., Conclusions: START is a practical surgical method. By employing the new two-step retraction method, we can maximize the cosmetic and functional benefits for patients and reduce the workload fatigue of surgeons by increasing robotic dependency., (© 2021. The Author(s).)

Background: Differentiated thyroid carcinoma with lateral neck lymph node metastasis requires aggressive operative intervention, including lateral neck dissection. Although several robotic approaches have made precise surgery for thyroid cancer possible, few centers have expanded the technique for application to lateral neck dissections. This study aimed to demonstrate the technical feasibility, cosmetic effectiveness, and safety of robotic transaxillary lateral neck dissection (RTLND) using the da Vinci system., Methods: From January 2008 to July 2019, 500 patients diagnosed with thyroid cancer with lateral neck node metastasis underwent RTLND. The clinicopathologic characteristics and surgical outcomes were retrospectively reviewed., Results: All operations were performed successfully without open conversion. As the primary operation for thyroid cancer, 476 (95.2%) patients underwent unilateral or bilateral RTLND, including robotic total thyroidectomy. The remaining 24 patients (4.8%), all of whom had a recurrence, also underwent RTLND with additional procedures, if needed. The mean operation time for the 500 operations was 293.71 ± 67.22 min. Only five cases had recurrence and required further treatment., Conclusions: RTLND is technically feasible and safe through the precise manipulation of robotic instruments. While this method is thorough and provides safe and effective surgical outcomes, it also offers the additional advantage of being minimally invasive., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker., Methods: LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results., Results: LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages., Conclusion: LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

Background: Thyroidectomy is the typical treatment for pediatric thyroid carcinoma; total thyroidectomy is commonly performed. We aimed to report our experience at a single tertiary institution and to evaluate the risk factors for recurrence, especially based on surgical extent, in pediatric patients with differentiated thyroid carcinoma (DTC)., Methods: A data of 94 pediatric patients who underwent thyroid surgery for DTC from January 1982 to December 2012 at Yonsei University Hospital (Seoul, Korea) were reviewed. The clinicopathologic features and surgical outcomes were retrospectively analyzed through complete chart reviews., Results: The mean age was 16.6 ± 3.0 (range, 5-19) years. Fourteen patients had recurrence. Tumor size >2 cm (hazard ratio [HR], 14.241; p = 0.011) and positive lymph nodes (HR, 1.056; p = 0.039) were significant risk factors for disease-free survival (DFS) in multivariate analysis. In Kaplan-Meier analysis, a statistically significant difference was noted in the DFS according to tumor size 2 cm (p < 0.001). However, the DFS was not significantly different between the bilateral total thyroidectomy (BTT) and less than BTT groups (p = 0.215)., Conclusions: BTT remains the treatment of choice in pediatric patients with DTC. Lobectomy may be considered for patients with limited disease, including those with tumor size <2 cm, no suspicious lymph nodes, intrathyroidal lesion, and no multifocal disease.

Purpose: Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis due to its indolent features. Only few studies have assessed the clinical factors that can predict lateral neck lymph node metastasis (LLNM) in patients with PTMC. This study aimed to examine the clinicopathological factors associated with LLNM in patients with PTMC., Methods: We reviewed medical records of 3578 patients with PTMC that was ≤1 cm in diameter on final pathology at Yonsei University Hospital between January 2015 and December 2017. The patients were divided into two groups (metastasis group [n = 157] and no metastasis group [n = 3421])., Results: The proportion of patients with multifocality, extrathyroidal extension (ETE), and central node metastasis was significantly higher in metastasis group (p < 0.001, p < 0.001 and p < 0.001, respectively), and the mean tumor size was relatively larger in metastasis group than in no metastasis group (0.7 ± 0.2 vs. 0.6 ± 0.2 cm, p < 0.001). However, no statistically significant differences were observed in the tumors harboring BRAF mutation between the two groups (84.8% vs. 80.6%, p = 0.199). Multivariate analysis indicated that the significant risk factors of LLNM include ETE (odds ratio [OR]: 1.904, 95% confidence interval [CI]: 1.267-2.861), multifocality (OR: 2.255, 95% CI: 1.544-3.293), and central node metastasis (OR: 7.768, 95% CI: 4.869-12.395), but not BRAF mutation (OR: 0.542, 95% CI: 0.337-0.874)., Conclusion: Approximately 4.4% of patients with PTMC presented with LLNM at the time of diagnosis. Moreover, the significant risk factors of LLNM include central node metastasis, ETE, and multifocal disease but not BRAF mutation.

Background: Many studies have shown the operative feasibility and safety of robotic thyroidectomy. However, there is still a concern on the operative invasiveness of robotic thyroidectomy owing to the wide flap dissection. The aim of this study was to introduce our novel robotic technique, which can minimize the dissection extent using the da Vinci SP robotic system. Methods : Ten patients underwent robotic transaxillary thyroidectomy using the da Vinci SP robotic system between December 2018 and April 2019 at Yonsei University Hospital (Seoul, Korea). All procedures were performed successfully using the single-port robotic system. Results : All 10 patients were women and diagnosed with papillary thyroid carcinoma. The mean operative time was 148.7 ± 26.8 minutes. The mean operative time using the gasless method was shorter than that using the gas insufflation method (130.5 ± 14.1 vs 176.0 ± 12.8 minutes). All patients were discharged on the third day after operation without any complications. Conclusions : Robotic transaxillary thyroidectomy using the da Vinci SP robotic system is technically feasible and safe with a short length of incision, shorter than what earlier reported. To our knowledge, this is the first study to use a single-port robotic system for thyroidectomy. To verify the superior operative outcomes, further clinical trials are necessary.

Background: Active surveillance is an alternative management for patents with low-risk papillary thyroid microcarcinoma (PTMC); however, there is an absence of specific molecular markers that predict its progression. We compared gene expression patterns between PTMC with lateral neck-node metastasis (N1b) and PTMC-lacking nodal metastasis (N0)., Methods: We performed oligonucleotide microarray analysis in three PTMCs without cervical lymph-node metastases (N0), and five PTMCs with lateral neck-node metastasis (N1b) at initial diagnosis, using an Illumina HumanHT-12 v4.0 Expression BeadChip. Quantitative real-time PCR (qPCR) and western blot analysis confirmed microarray data. We performed immunohistochemistry (IHC) to confirm protein overexpression in samples from 20 N0 and 24 N1b PTMC patients who underwent thyroidectomy., Results: Microarray analyses identified 52 probes corresponding to 45 genes. Expression of these genes differed significantly between the two PTMC groups. Forty genes were significantly upregulated and five genes were downregulated in N1b PTMC compared to N0. Four genes related to epithelial-to-mesenchymal transition (EMT) and stem cell markers, including ALDH1A3, TM4SF1, PROM1, and CAV1 were significantly upregulated in N1b PTMCs. Real-time qPCR confirmed this expression and western blot analysis confirmed higher expression of ALDH1A3, TM4SF1, PROM1, and CAV1 in N1b than in N0 PTMCs. IHC indicated overexpression of ALDH1A3 and CAV1 in N1b compared to N0 PTMCs., Conclusions: Genes related to EMT and thyroid cancer stem cell-like properties are upregulated in early extensive lymphatic spread of PTMC., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Understanding how comorbidities contribute to death in cancer patients is becoming an important topic. The present study assessed the role of comorbidities in overall mortality and causes of death in patients with differentiated thyroid carcinoma (DTC). This retrospective cohort study included 2070 patients who underwent thyroidectomy for DTC at a single institution between 2002 and 2005. Probabilities of overall, DTC-specific and other-cause death were examined according to the number of comorbidities, with consideration for competing events. The estimated 15-year cumulative incidences of overall, DTC-specific, and other-cause death were 7.3%, 1.6%, and 5.7%, respectively. Taking the group without comorbidities as a reference, we found that the group with 1-2 comorbidities and the group with ≥3 comorbidities had higher probabilities of other-cause death (subhazard ratios = 2.48 and 9.41, respectively; p < 0.01) and consequently shorter overall survival (hazard ratio = 1.95 and 5.33, respectively; p < 0.01), with adjustment for age, sex, and tumor-node-metastasis classification. In contrast, the probability of DTC-specific death was reduced in patients with ≥3 comorbidities (subhazard ratio = 6.81e-10, p < 0.01). For overall death, the relative proportion of death from DTC reduced when the number of comorbidities increased, and DTC-specific death was not observed in patients with ≥3 comorbidities. Our results show that death from DTC itself accounted for only a fraction of the overall deaths among patients who underwent surgery for DTC. Comorbidities increased overall mortality by increasing the probability of other-cause death. Patients with multiple comorbidities had a low probability of dying from DTC because they died earlier from comorbidities.

Background: Extensive extrathyroidal extension (ETE) has a significant role in the prognosis of papillary thyroid cancer (PTC) without distant metastasis, but its role in PTC with initial distant metastasis has never been studied. This study aimed to evaluate the prognostic significance of extensive ETE regarding disease progression, survival, and remission in PTC patients with initial distant metastasis., Methods: This retrospective cohort study included PTC patients with initial distant metastasis who underwent total thyroidectomy with a median follow-up period of 6.7 years. The prognostic significance of extensive ETE was assessed in terms of time to tumor progression (TTP), cancer-specific survival (CSS), and cumulative incidence of remission with all-cause death as the competing event., Results: The study enrolled 64 patients. Of these patients, 21 (32.8%) had extensive ETE, which was associated with a shorter TTP (adjusted hazard ratio [HR], 4.10; p = 0.015) and a lower CSS rate (p = 0.002, log-rank), particularly for patients 55 years of age or older with stage 4b disease (10-year CSS rate: 33.3% in those with and 92.3% in those without extensive ETE; p = 0.017). Additionally, remission was observed only in patients without extensive ETE (10-year cumulative incidence of remission: 0.0% in those with and 29.3% in those without extensive ETE; p = 0.013)., Conclusions: Extensive ETE of the primary lesion results in poorer prognoses for PTC patients with initial distant metastasis. The high CSS rate for patients with stage 4b PTC but no extensive ETE indicates that the prognosis of this patient population should be distinguished from that of other stage 4 cases.

This study aimed to compare the clinicopathologic characteristics and oncologic outcomes of papillary thyroid cancer (PTC) patients according to sex. Then, we validated prognostic variables to determine whether sex is a significant prognostic factor for PTC.Between January 2007 and December 2010, 1232 men and 7276 women PTC patients underwent surgery. The patient characteristics and 5-year oncologic outcomes were compared. The stepwise Cox proportional hazards model determined the significance of survival variables.Men PTC patients had more lymph node (LN) metastases than women, both in the total (P < .0001) and hemithyroidectomy (P < .0001) patients. Men and women showed similar 5-year recurrence-free survivals, both in total (P = .815) and hemithyroidectomy (P = .148) patients. The tumor size and the number of positive central nodes were associated with tumor recurrence, but not sex.Sex was not an independent prognostic factor for tumor recurrence. Multicenter clinical studies with long-term follow-ups are needed to validate these results.

Background: The optimal period of low iodine diet during preparation for radioactive iodine (RAI) ablation in an area with iodine-rich diet was investigated., Methods: Ninety-four patients with thyroid cancer who underwent low iodine diet and RAI were prospectively allocated into 2 groups-thyroxine withdrawal or using recombinant human thyroid stimulating hormone (rhTSH) for TSH stimulation. Their urinary iodine excretion (UIE) patterns were analyzed., Results: There was no clinicopathological difference between the 2 groups except for tumor size and lymph node status. The UIE (median iodine to creatinine ratio, I/Cr) in the withdrawal group on the 7th and 14th day were 18.3 and 17.9 μg/gCr, respectively, with adequate preparation rate of 93.3% on both days (cutoff value 100 μg/gCr). In the rhTSH group, the median I/Cr on the 7th and 14th day were 48.0 and 45.7 μg/gCr (adequate preparation rates 91.8% and 93.8%), respectively., Conclusion: One week of low iodine diet is sufficient preparation for RAI regardless of method of TSH stimulation., (© 2018 Wiley Periodicals, Inc.)

Background: Recent guidelines advocate unilateral thyroidectomy for low-risk 1-cm to 4-cm differentiated thyroid cancer (DTC). This study was designed to examine the association between the extent of thyroidectomy and oncologic outcomes in patients with 1-cm to 4-cm DTC., Materials and Methods: From April 1978 to December 2011, 16 057 patients with DTC underwent thyroidectomy at Yonsei University Hospital. Among them, 5266 (32.8%) patients were classified as having 1-cm to 4-cm DTC and were enrolled in this study. Clinicopathologic features and prognostic results (disease-free survival [DFS] and disease-specific survival [DSS] rates) were analyzed by retrospective medical record review. The mean follow-up duration was 57.3 ± 58.1 months., Results: Of tumor subtypes in the study group, papillary thyroid carcinoma was the most common (97.5%) and follicular thyroid carcinoma occurred at a rate of 2.5%. In this study, the mean tumor size was 1.84 ± 0.74 cm. Patients had extrathyroidal extension (69.3%), multiplicity (35.1%), bilaterality (26.4%), central lymph node metastasis (53.0%), and lateral neck node metastases (19.9%). Of the 5266 patients, 4292 (81.5%) underwent total thyroidectomy and 974 (18.5%) had lobectomies. Recurrence rates in the total thyroidectomy and lobectomy groups were 5.7% and 9.4%, respectively. The lobectomy group had lower DFS (P = .007) and higher DSS (P = .034) than the total thyroidectomy group. A multivariate analysis for DFS revealed that tumor size, N classification, and extent of thyroidectomy were independent risk factors. On multivariate analysis, independent risk factors for DSS were age, sex, tumor size, and M classifications., Conclusion: Although extent of thyroidectomy does not affect DSS, total thyroidectomy is beneficial for reducing recurrence in patients with 1-cm to 4-cm DTC. However, if such tumors have such low-risk features as being unifocal, intrathyroidal, and lymph node metastasis-negative, extent of thyroidectomy does not affect oncologic outcome and lobectomy may be sufficient., (© 2018 Wiley Periodicals, Inc.)

Background: Diffuse lymphocytic infiltration (DLI) is frequently found with papillary thyroid cancer (PTC), so there has been long interest in how it affects the characteristics of PTC. This purpose of this study was to define the association between DLI and PTC aggressiveness according to thyroperoxidase antibody (TPOAb) and B-type Raf (BRAF) V600E mutation positivity., Methods: There were 1879 patients with PTC who underwent surgery and were enrolled in this study. Clinicopathologic characteristics were compared between groups according to the presence of DLI and TPOAb. Multiple logistic regression analysis was conducted to assess odds ratio (OR) for each dependent variable (BRAF V600E mutation, tumor size >1.0 cm, multifocality, extrathyroidal extension, and lymph node metastasis) of each group according to the presence of DLI and TPOAb, with the group with neither DLI or TPOAb (DLI-negative TPOAb-negative PTC) as the reference., Results: The DLI-positive PTC showed more frequent multifocality and less frequent BRAF V600E mutation than DLI-negative PTC. Among patients with DLI-positive PTC, extrathyroidal extension and BRAF V600E mutation was less frequent when serum TPOAb was positive. In multiple logistic regressions, DLI-positive TPOAb-positive PTC showed a high OR for multifocality (1.410; P = .017), but low ORs for BRAF V600E mutation (0.521; P < .001) and extrathyroidal extension (0.691; P = .008). The patients with DLI-positive TPOAb-positive PTCs showed a high OR for multifocality (1.588; P = .002), and high ORs for tumor size >1.0 cm (2.205; P = .019) and lymph node metastasis (2.005; P = .032) in subgroup analyses of PTC with wild-type BRAF. The DLI-negative TPOAb-positive group was not associated with any tumor aggressiveness-related variables., Conclusion: Although DLI was associated with multifocality regardless of TPOAb positivity, it was associated with an indolent feature when TPOAb was positive but with aggressive features in PTC with wild-type BRAF when TPOAb was negative. The TPOAb and BRAF status may help to define the clinical implication of lymphocytic infiltration found with PTC., (© 2018 Wiley Periodicals, Inc.)

Background: Hereditary medullary thyroid carcinoma can present as a part of multiple endocrine neoplasia syndrome by rearranged during transfection gene mutation. We evaluated the prevalence of rearranged during transfection gene mutation in patients who have medullary thyroid carcinoma and the correlations of genotype with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism according to the revised American Thyroid Association risk level., Methods: A total of 331 patients were diagnosed with medullary thyroid carcinoma, 172 of whom were tested for the rearranged during transfection germline mutation by sequencing of exon 8, 10, 11, and 13-16. These patients were diagnosed during the years 1982-2012 at 2 Korean tertiary hospitals. Patients were analyzed according to the route of diagnosis (screened versus index cases) or the mutational site of rearranged during transfection gene (the American Thyroid Association risk group)., Results: Rearranged during transfection mutation was found in 23.8% of patients tested, showing a decreasing trend with time. The most commonly mutated codon was codon 634 (37.1%), followed by codon 918 (14.3%). rearranged during transfection-positive patients were younger than rearranged during transfection-negative patients, although no other clinicopathologic characteristics differed. Screened cases were younger and had smaller tumors than index cases. Among rearranged during transfection-positive patients, pheochromocytoma manifested in 35.1% and hyperparathyroidism in 7.0%. Notably, pheochromocytoma and hyperparathyroidism emerged at any time after the diagnosis of medullary thyroid carcinoma. The American Thyroid Association risk-group analysis demonstrated that medullary thyroid carcinoma patients in the highest risk group were younger, had larger tumors, and higher disease-specific mortality. Similar results for pheochromocytoma were found, according to the American Thyroid Association risk group, although the results were not significant., Conclusions: Korean patients who have medullary thyroid carcinoma showed a similar distribution of rearranged during transfection gene mutation with those in Western countries. The American Thyroid Association risk classification was shown to be useful for pheochromocytoma, as well as for medullary thyroid carcinoma. Familial screening for rearranged during transfection mutation and lifelong monitoring for associated pheochromocytoma should be emphasized in hereditary medullary thyroid carcinoma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Since the use of robot systems in thyroid surgery was introduced in 2007, we have advanced a novel method of robotic thyroidectomy (RT) using a gasless transaxillary approach (TAA). We report our experience with this technique and detail the surgical outcome of 5000 robotic thyroidectomies., Methods: From October 2007 to May 2016, we successfully performed 5000 robotic thyroidectomies using a gasless TAA at the Department of Surgery, Yonsei University Health System. The medical records of the patients are reviewed retrospectively, and the details of clinicopathologic characteristics, operation times, perioperative complications, and oncologic outcomes are analyzed., Results: The 5000 patients with thyroid tumor (4804 with cancer and 196 with benign tumor) underwent RT using a gasless TAA. Mean operation time was 134.5 ± 122.0 min. The most common histologic subtype of thyroid cancer was papillary (98%), and the mean tumor size was 8.0 ± 6.0 mm. Stage I was found in 85.4% patients regarding tumor nodes metastasis staging. The 196 benign tumors consisted of 104 adenomatous hyperplasias (53.0%), 43 follicular adenomas (21.9%), 30 Graves' diseases (15.3%), and 19 others (9.7%). Postoperative complication occurred in 24.1% without any serious one, and overall morbidity tended to decrease over time. No disease-specific mortality was observed during the follow-up period. Locoregional recurrence was developed in 26 patients (0.5%)., Conclusion: The authors have tried to improve RT technique using gasless TAA and achieved acceptable surgical outcomes. The rapid evolution of surgical robot technology and our constant effort to advance RT technique using gasless TAA would make it possible to reduce the perioperative morbidity and gain the best possible operative and oncologic outcomes.

Recently, dynamic risk stratification has been found to be more valuable than static anatomic staging system in nonmedullary thyroid cancer and this strategy has also been accepted in medullary thyroid cancer (MTC). The present study was designed to compare the clinical usefulness of response to initial therapy stratification with a traditional anatomic staging system.From August 1982 to December 2012, a total of 144 MTC patients underwent thyroidectomy in Yonsei University Hospital. Among them, 117 (82.2%) patients with complete clinical data and sustained follow-up were enrolled in this study. Clinicopathological features and surgical outcomes were analyzed by retrospective medical chart review. Mean follow-up duration was 85.78 ± 62.51 months.In this study, mean tumor size was 1.94 ± 1.40 cm and 22 (18.9%) patients had hereditary MTC; 95 (81.1%) patients had sporadic MTC. Stage I patients had highest probability of excellent response to initial therapy (92.1%). Stage IV patients had highest probability of biochemical and structural incomplete response to initial therapy (57.5% and 30.3%) and lowest probability of excellent response to initial therapy (12.1%). Both response to initial therapy stratification and TNM staging system offered useful prognostic information in this study. The TNM staging system provided risk stratification pertaining to disease-free survival (DFS), disease-specific survival (DSS), and the probability of having no evidence of disease at final outcome, but did not provide risk stratification pertaining to the probability of having biochemical persistent/recurrence disease at final outcome. However, response to initial therapy stratification provided risk stratification pertaining to not only DFS, DSS, and the probability of having no evidence of disease at final outcome but also the probability of having biochemical persistent/recurrence disease at final outcome.In this study, we demonstrated that dynamic risk stratification with adjusted response to initial therapy system can offer more useful prognostic information than anatomic staging system in MTC., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: The aim of this study is to compare the feasibility and oncologic safety of Single-incision, gasless, Endoscopic trans-axillary bilateral Total thyroidectomy (SET) with open cervical total thyroidectomy in patients with papillary thyroid carcinoma (PTC)., Materials and Methods: From March 2008 to December 2012, PTC patients underwent bilateral total thyroidectomy. Conventional, open surgery was performed on 538 patients (Group O) and endoscopic surgery was performed on 200 patients (Group E). We analyzed the patient's clinicopathologic, postoperative complications, and surgical completeness., Results: The mean ages of the patients were 48.9 ± 0.5 (range = 24-77) in Group O and 39.5 ± 0.8 (range = 17-73) in Group E with statistical significance (P < .001). Percentage of female patients were 74.3% in Group O and 96.0% in Group E with statistical significance (P < .001). The postoperative hospital stay in Group O was significantly longer than Group E (4.60 ± 0.05 versus 3.30 ± 0.05; P < .001). The operation time in Group E was significantly longer than Group O (93.9 ± 1.3 versus 142.6 ± 3.3; P < .001). More transient hypocalcemia was found in Group O compared to Group E with statistical significance (28.1% versus 22.4%; P < .001). There were no significant differences with respect to permanent hypocalcemia, permanent recurrent laryngeal nerve palsy, seroma, and hematoma. The mean 1 year-stimulated sTg was 0.23 ± 0.03 and 0.18 ± 0.02 in Group O and E, respectively. Tumor recurrence during short-term follow-up at neck ultrasonography (1 year) was detected in 4 patients in Group O., Conclusion: SET is safe and effective, not only for low-risk patients with early-detected cancer, but also for selected cases of advanced cancer.

Background: Robotic modified radical neck dissection (MRND) using a gasless transaxillary approach has been reported to be a safe and meticulous technique in patients with papillary thyroid carcinoma (PTC) and lateral neck node metastasis (N1b). Few studies, however, have attempted to assess the long-term oncologic outcomes of robotic MRND in these patients. This study aimed to compare perioperative and 5-year oncologic outcomes of robotic MRND with conventional open procedures in patients with N1b PTC., Methods: Between September 2007 and February 2010, 193 patients with N1b PTC underwent total thyroidectomy and MRND by a single surgeon. Of these, 42 (21.8 %) underwent robotic procedures and 151 (78.2 %) underwent conventional open procedures. All patients received 3.7- to 5.5-GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBSs), and diagnostic WBS (DxWBSs) during follow-up. An exact 1:3 matching for age and stage was performed to minimize selection bias, and perioperative and 5-year oncologic outcomes were compared in the matched groups., Results: The mean follow-up period was 66.0 months (range 60-90 months). Number of retrieved cervical lymph nodes (LNs) (p = .102) and postoperative ablation success rates (p = .864) were similar between the two groups. TSH-suppressed serum Tg concentrations after 5 years (0.7 ± 1.5 vs. 2.4 ± 14.1 ng/ml; p = .471) and recurrence rates in the robotic and open groups (1/41 [2.4 %] vs. 3/102 [2.9 %]; p = .864) were similar for the 5-year follow-up period. Four patients experienced recurrence: Three exhibited regional lymph node metastasis, and one showed bilateral lung metastases., Conclusion: The perioperative and 5-year oncologic outcomes were similar after robotic and conventional open MRND. Large, prospective randomized controlled trials with long-term follow-up data are needed to validate these results.

Background: The 2015 American Thyroid Association (ATA) management guidelines for adult patients with differentiated thyroid cancer propose the use of the modified initial risk stratification and response to therapy re-stratification systems. This study was conducted to validate the practicality of the revised guidelines for predicting tumor recurrence in patients with differentiated thyroid cancer., Methods: Patients with papillary thyroid cancer (n = 2425) who underwent total thyroidectomy with central neck node dissection with or without modified radical neck node dissection at a single institution between October 1985 and July 2009 were retrospectively enrolled. The accuracy of three different risk-stratification strategies for predicting disease-free survival, set out in the 2009 and 2015 ATA management guidelines, was assessed: the initial risk stratification (ATA 2009-RSS), the modified initial risk stratification (ATA 2015-RSS), and the response to therapy re-stratification (ATA 2015-RTR)., Results: After applying the ATA 2015-RSS, 258/1913 (13.5%) of patients originally designated as intermediate risk by the ATA 2009-RSS were designated as low risk. This was mainly due to the small number of metastatic lymph nodes. Recurrence was detected in 136 (5.6%) patients during follow-up. Of the 2425 cases examined, 375 were designated as low risk by the ATA 2009-RSS, with a recurrence rate of 1.1%. However, the ATA 2015-RSS designated 633 (26.1%) cases as low risk, with a recurrence rate of 0.9%. Implementing the ATA 2015-RTR predicted an excellent response in 1597 (65.9%) cases, with a recurrence rate of 1.1%. According to the proportion of variance explained (PVE), the Akaike information criterion, Harrell's c index, and integrated area under the curve, comparing the predictive accuracy of the ATA 2009-RSS, ATA 2015-RSS, and ATA 2015-RTR revealed that the ATA 2015-RTR was a superior predictor of recurrence., Conclusions: A proportion of patients designated as intermediate risk by the ATA 2009-RSS were designated as low risk by the ATA 2015-RSS. The ATA 2015-RTR may be the most accurate predictor of risk of recurrence.

Objective: In the current study, we examined whether selenium supplementation during iodine-131 ( 131 I) treatment had a radio-protective effect on salivary glands., Subjects and Methods: Sixteen patients with differentiated thyroid cancer were prospectively enrolled in the study. Patients after total thyroidectomy, before 131 I treatment, were divided into two groups; 8 patients in the selenium group and 8 patients in the control group. Patients in the selenium group received 300νg of selenium orally for 10 days, from 3 days before to 6 days after 131 I treatment. The control group received a placebo over the same period. To assess salivary gland function, salivary gland scintigraphy was performed before and 6 months after 131 I treatment. Serum amylase and whole blood selenium levels were measured before and 2 days and 6 months after 131 I treatment. Using salivary gland scintigraphy, maximum uptake ratio (MUR), maximum secretion percentage (MSP), and ejection fraction (EF) of each salivary gland were calculated., Results: Baseline clinical characteristics, baseline amylase and selenium levels, and parameters of baseline salivary gland scintigraphy were not significantly different between selenium and control groups (P>0.05). On a blood test performed 2 days after 131 I treatment, the selenium group showed a significantly higher whole blood selenium level (P=0.008) and significantly lower serum amylase level (P=0.009) than the control group. On follow-up salivary gland scintigraphy, the control group showed significantly decreased, MUR of the bilateral parotid and left submandibular glands, MSP of the bilateral parotid and submandibular glands, and EF of the left submandibular glands (P<0.05), while the selenium group only had a significant decrease in MSP of the right submandibular gland and EF of the left submandibular gland (P<0.05)., Conclusion: Selenium supplementation during 131 I treatment was effective to reduce salivary glands damage by 131 I radiation in patients with differentiated thyroid cancer.

Purpose: The role of the robot in thyroid surgery remains uncertain, and it is unclear whether robotic total thyroidectomy (R-TT) can be justified as a standard treatment for patients with thyroid cancer. This study compared the long-term operative results and oncologic outcomes of R-TT and conventional open TT (O-TT) after propensity score matching of the cohorts., Methods: This study retrospectively evaluated patients with papillary thyroid cancer (PTC) who underwent TT with central compartment node dissection (CCND) by a single surgeon in tertiary medical center. Of the 833 patients, 94 (11.3 %) were lost to follow-up. 245 (33.2 %) underwent R-TT, and 494 (66.8 %) underwent O-TT. The mean follow-up duration was 74 (range 61-91) months. Propensity score matching in age, gender, tumor size, extrathyroidal invasion, multiplicity, bilaterality, and TNM stage identified 206 pairs of patients. The long-term oncologic outcomes were assessed in the R-TT and O-TT groups before and after adjustment for baseline covariates., Results: After adjustment for baseline covariates, serum thyroglobulin (Tg) (p = 0.746) and anti-thyroglobulin antibody (TgAb) (p = 0.394) concentrations were similar in the two groups 5 years after surgery. Nine patients experienced locoregional recurrence, six in the O-TT and three in the R-TT group, with all recurrences in regional LNs. Disease-free survival (DFS) was similar in the R-TT and O-TT groups before matching (p = 0.890) and after adjustment for baseline covariates (p = 0.882)., Conclusion: This represents the first report of 5-year surgical outcomes in patients who underwent R-TT for thyroid cancer. Long-term oncologic quality was similar after R-TT and O-TT.

Context: The increase in thyroid screening in the general population may lead to earlier detection of medullary thyroid carcinoma (MTC)., Objective: We aimed to evaluate secular trends in clinicopathological characteristics and long-term prognosis of MTC and its prognostic factors., Design: This was a retrospective analysis from 1982 to 2012., Patients: 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)., Measurements: These included recurrence and mortality as well as biochemical remission (BCR) of serum calcitonin., Results: Mean tumour size (from 2·5 cm to 1·7 cm, P < 0·001) 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%, P < 0·001). 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; P < 0·001). Male gender (HR = 3·18, 95% CI 1·18-8·56; P = 0·022), tumour size >2 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., Conclusions: Clinicopathological characteristics and recurrence of MTC improved with time. Po-BCR was the best predictive factor for recurrence-free survival., (© 2015 John Wiley & Sons Ltd.)

Regional lymph node (LN) metastasis has a significant impact for prediction of recurrence in patients with papillary thyroid cancers (PTC); however, the prognostic value of the lymph node ratio (LNR), which is defined as the ratio of the number of metastatic LNs to the total number of investigated LNs, is controversial. In this study, we determined the optimal cut-off values of LNRs for the prediction of recurrence in PTC patients.This large cohort study retrospectively evaluated 2294 patients who had undergone total thyroidectomy for PTC at a single institution from October 1985 to June 2009. The prediction probability of central LNR (cLNR, level VI) and total LNR (tLNR, levels II-VI) were estimated by binominal logistic regression analysis. Hazard ratios of the cut-off LNR values for cancer recurrence were calculated for relevant covariates using multivariate Cox regression analyses. Kaplan-Meier analyses were also utilized to assess the effects of estimated LNR cut-off values on recurrence-free survival (RFS).Of the 2294 patients, 138 (6.0%) presented cancer recurrence during the follow-up period (median duration = 107.1 months). The prediction probability indicated that LNRs of 0.4 and 0.5 for central LN and total LN, respectively, are optimal cut-off values for precise prediction with minimization of outliers. Multivariate Cox regression analyses revealed that cLNR ≥0.4 was independently predictive of recurrence in patients with N0 and N1a PTCs (hazard ratio [HR]: 7.016, 95% confidence interval [CI]: 3.72-12.986, P < 0.001) and that tLNR ≥0.5 indicated a significantly increased risk of recurrence in patients with N1b PTCs (HR: 2.372, 95% CI: 1.458-3.860, P < 0.001). In addition, Kaplan-Meier analyses clearly demonstrated that these LNR cut-off values are precisely operational in RFS estimation.The cut-off LNR values of 0.4 and 0.5 for cLNR and tLNR, respectively, were identified. Risk stratification combined with these LNR cut-off values may prove useful to determine treatment and follow-up strategies for PTC patients.

Recent functional genomic studies revealed that the oncogenic activity of focally amplified lncRNA on chromosome 1 (FAL1, ENSG00000228126) contributes to tumor growth by p21 repression in human cancers. However, the expression of FAL1 was not investigated in papillary thyroid cancer (PTC). We aimed to determine if FAL1 was up-regulated in PTC compared to paired contralateral normal thyroid tissues, and to investigate the potential targets of this lncRNA and its clinicopathological significance in PTC. We analyzed FAL1 and p21 expression levels in 100 PTC samples and matched normal thyroid tissue by qRT-PCR. Using lncRNA microarray data from the Gene Expression Omnibus (accession no. GSE61763), we explored potential targets of FAL1 by Gene Set Enrichment Analysis, followed by verification by qRT-PCR in our PTC samples. A cross-sectional observational study was conducted to investigate the relationship between patients' clinicopathological features and FAL1 expression. FAL1 expression was significantly higher in PTC than in paired normal thyroid tissues (paired t test, P < 0.001). p21 mRNA expression was also increased, not decreased, in PTC, and had no correlation with FAL1 expression (r = 0.0897, P = 0.4002). Gene Set Enrichment Analysis, using publicly available microarray data, indicated that a gene set related to the cell cycle, including E2F transcription factors 1 and 2, and cyclin D1, was coordinately enriched among samples with high FAL1 expression. A volcano plot showed that E2F1, E2F2, and VEGFA mRNAs were increased in the high FAL1 samples. In clinicopathological analyses, multifocality was more frequently observed in PTC patients with high FAL1 (P = 0.018). Multivariate analysis showed that high FAL1 expression increased the risk of multifocality (after adjustment for clinical variables, OR = 4.019, CI = 1.041-11.020, P = 0.043). FAL1 may have a role in cell-cycle progression and may be associated with aggressive tumor behavior in PTC., Competing Interests: The authors have no conflicts of interest to disclose.

Background: The prevalence of papillary thyroid cancer (PTC) is thought to be related to obesity, which affects the prognosis for PTC patients. However, the mechanisms implicated in the relationship between obesity and PTC is a matter for debate. In this study, we aimed to gain insight into the relationship between obesity and the clinicopathological features of PTC, including the BRAFV600E mutation., Methods: The medical records of 1121 PTC patients were reviewed and the relationships between anthropometric factors, biochemical parameters, and clinicopathological parameters, including BRAFV600E mutation status, were analyzed., Results: Body mass index (BMI) showed a strong association with advanced TNM stage (p < 0.001) and BRAFV600E mutation status (p = 0.008). We also found that BRAFV600E (+) patients had a higher body weight (p = 0.024) and a higher BMI (p = 0.003) than patients with BRAFV600E (-) PTC. In addition, BRAFV600E (+) PTC patients had a significantly higher incidence of extrathyroidal extension (p = 0.025) and more advanced T, N, TNM stage (p < 0.001) than BRAFV600E (-) PTC patients. Consistent with this observation, female BRAFV600E (+) PTC patients had a higher BMI (p = 0.011) and more aggressive tumor behaviors than female BRAFV600E (-) PTC patients. In multivariate analysis, BMI was persistently associated with BRAFV600E mutation in the entire cohort (odds ratio [OR] 1.387; 95 % CI 1.036-1.859; p = 0.028) and in the female subcohort (OR 1.221; 95 % CI 1.014-1.631; p = 0.046)., Conclusion: The positive association between BMI and BRAFV600E supports the hypothesis that excessive bodyweight influences tumor progression.

Background: This study assessed the results of robotic thyroidectomy by fellowship-trained surgeons in their initial independent practice, and whether standard fellowship training for robotic surgery shortens the learning curve., Methods: This prospective cohort study evaluated outcomes in 125 patients who underwent robotic thyroidectomy using gasless transaxillary single-incision technique by 2 recently graduated fellowship-trained surgeons. Learning curves were analyzed by operation time, with proficiency defined as the point at which the slope of the time curve became less steep., Results: Of the 125 patients, 113 underwent robotic less-than-total thyroidectomy, 9 underwent robotic total thyroidectomy and 3 underwent robotic total thyroidectomy with modified radical neck dissection. Mean total times for these 3 operations were 100.8 ± 20.6 minutes, 134.2 ± 38.7 minutes, and 284.7 ± 60.4 minutes, respectively. For both surgeons, the operation times gradually decreased, reaching a plateau after 20 robotic less-than-total thyroidectomies., Conclusion: The surgical learning curve for robotic thyroidectomy performed by recently graduated fellowship-trained surgeons with little or no experience in endoscopic surgery showed excellent results compared with those in a large series of more experienced surgeons., (© 2014 Wiley Periodicals, Inc.)

Background: The purpose of this study was to investigate the correlation between B-type Raf (BRAF) kinase mutation and clinicopathological features of follicular variant of papillary thyroid carcinoma (PTC)., Methods: Eighty-four patients with pathologically confirmed follicular variant of PTC, who underwent a preoperative BRAF(V600E) study, were analyzed. Clinicopathological parameters and ultrasonographic features were compared between the BRAF(V600E) -positive and negative groups., Results: A total of 41.7% of the patients showed BRAF(V600E) . The BRAF(V600E) -positive group showed the smaller tumor size (7.3 ± 3.6 mm vs 10.7 ± 8.9 mm; p = .018) and the more frequent multifocality (25.7% vs 8.2%; p = .028). Follicular variant of PTC with BRAF(V600E) showed suspicious ultrasonographic features (88.6% vs 57.1%; p = .002) more frequently. BRAF(V600E) positivity is associated with multifocality after adjusting for age, sex, the presence of suspicious ultrasonographic features, pathological tumor size, and thyrotropin level., Conclusion: BRAF(V600E) was correlated with smaller tumor size and suspicious ultrasonographic features in follicular variant of PTC. BRAF(V600E) was a significant parameter for predicting multifocality of follicular variant of PTC., (© 2014 Wiley Periodicals, Inc.)

Background: The association between the BRAF mutation and persistence/recurrence was investigated in patients with classical papillary thyroid carcinoma (PTC) at a BRAF mutation prevalent area., Methods: A total of 282 patients with total thyroidectomy and prophylactic central neck dissection were included in this study. The BRAF mutation was evaluated with cytology specimen using dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) and direct sequencing preoperatively., Results: Thirty-four patients (12%) had persistence/recurrence. In all PTC, the BRAF mutation on both methods was not associated with persistence/recurrence. In PTC >10 mm, the BRAF mutation on DPO-based multiplex PCR was significantly associated with persistence/recurrence and a potential predictor for persistence/recurrence. In PTC ≤10 mm, none of the covariates were significantly different between patients with and without persistence/recurrence., Conclusion: The BRAF mutation was significantly associated with persistence/recurrence and a potential predictor in patients with classical PTC >10 mm at a BRAF mutation prevalent area., (© 2015 Wiley Periodicals, Inc.)

Background: This phase 2 study investigated the efficacy and safety of dovitinib (TKI258), a receptor tyrosine kinase inhibitor with potent activity against fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR), in locally advanced or metastatic thyroid cancer patients., Patients and Methods: Patients with advanced thyroid cancer that was refractory or not appropriate for (131)I received dovitinib orally, 500mg once daily for five consecutive days, followed by a 2-day rest every week. The primary end-point was objective response rate. Secondary end-points were progression-free survival (PFS), overall survival (OS), duration of response, changes in tumour markers and safety., Results: Between January 2013 and October 2014, a total of 40 patients were enrolled. There were 23 (57.5%) papillary thyroid cancer, 12 (30%) medullary thyroid cancer and 5 (12.5%) follicular thyroid cancer patients. One patient had withdrawn consent before the administration of dovitinib. The overall response rate was 20.5% (8/39) and disease control rate was 69.1% (26/39). Median PFS was 5.4 months (95% confidence interval (CI), 2.0-8.8) and median OS was not reached with 8.4 months follow-up duration. Common treatment-related adverse events were diarrhoea (53.8%), anorexia (35.8%), vomiting (25.6%), fatigue (23%) and nausea (20.5%), most of which were grade 1 or 2. There were no grade 4 events or treatment-related deaths. Dose interruption occurred in 12 (30.7%) patients, and 19 (48.7%) patients experienced dose reduction due to adverse events., Conclusions: Dovitinib has a modest activity with manageable toxicity in locally advanced or metastatic thyroid cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Although some studies have reported that preoperative vitamin D deficiency (VDD) is a risk factor for hypocalcemia after total thyroidectomy (TT) in patients with nontoxic multinodular goiter or Graves' disease, the association between VDD and postoperative hypocalcemia in thyroid cancer patients undergoing TT plus central compartment neck dissection (CCND) remains unclear. This study evaluated whether preoperative VDD was associated with postoperative symptomatic hypocalcemia., Materials and Methods: Data were collected prospectively between September 2012 and May 2013. A total of 267 consecutive thyroid cancer patients who underwent TT with CCND were analyzed. Patients were divided into two groups--VDD or non-VDD--by preoperative vitamin D level of <10 or ≥10 ng/mL. Symptomatic hypocalcemia was defined as serum calcium <8.2 mg/dL and symptoms or signs of hypocalcemia. The rates of postoperative symptomatic hypocalcemia and clinicopathological features were compared between the two patient groups., Results: The rate of postoperative symptomatic hypocalcemia was higher in the VDD group than in the non-VDD group (43.8% vs. 30.4%, p=0.043). By logistic regression analysis, predictive factors for postoperative symptomatic hypocalcemia included a preoperative vitamin D level of <10 ng/mL (p=0.007; odds ratio=3.00). In patients who had postoperative intact parathyroid hormone (iPTH) levels <15 pg/mL, symptomatic hypocalcemia was more common in the VDD group than in the non-VDD group (77.5% vs. 53.2%, p=0.008). The findings show that a preoperative vitamin D threshold level of >20 ng/mL reduced the risk of symptomatic hypocalcemia by 72% when compared with patients with VDD (p=0.003)., Conclusion: VDD is significantly associated with postoperative symptomatic hypocalcemia in thyroid cancer patients undergoing TT plus CCND. VDD was predictive for symptomatic hypocalcemia when patients had postoperative serum iPTH levels <15 pg/mL. Thus, preoperative supplementation with oral vitamin D should be considered to minimize postoperative symptomatic hypocalcemia.

Background: Acellular dermal matrix (ADM) has been used for antiadhesion formation along with wound healing in various surgical fields., Objective: The aim is to assess the efficacy of ADM implantation in the prevention of postoperative scars and adhesions after conventional, open, total thyroidectomy., Materials and Methods: Forty-four patients with papillary thyroid carcinoma undergoing thyroidectomy were randomly assigned to the study (ADM implantation) or control group (without ADM). Global photographic assessment, Vancouver scar scale (VSS), objective scar assessment, and swallowing impairment index were assessed at baseline, immediately after surgery, and at 1 and 2 months after surgery., Results: Nineteen control and 20 study group participants completed the study. The mean VSS score of the study group was significantly lower than the controls at both 1 month (3.06 ± 1.25 vs 4.41 ± 1.54, respectively) and 2 months (2.76 ± 1.56 vs 4.35 ± 1.58, respectively) after surgery. Scar quality measures (mean melanin and erythema indexes) were significantly lower in the study group compared with controls. Study group participants had significantly lower swallowing impairment scores than controls. The mean postoperative hospitalization of both groups was not significantly different., Conclusion: Acellular dermal matrix-assisted implants appear to improve post-thyroidectomy scar and swallowing impairments without delays in operation time.

Purpose: The radioiodine ablation therapy is required for patients who underwent a total thyroidectomy. Through a comparative review of a low iodine diet (LID) and a restricted iodine diet (RID), the study aims to suggest guidelines that are suitable for the conditions of Korea., Materials and Methods: The study was conducted with 101 patients. With 24-hour urine samples from the patients after a 2-week restricted diet and after a 4-week restricted diet, the amount of iodine in the urine was estimated. The consumed radioiodine amounts for 2 hours and 24 hours were calculated., Results: This study was conducted with 47 LID patients and 54 RID patients. The amounts of iodine in urine, the 2-week case and 4-week case for each group showed no significant differences. The amounts of iodine in urine between the two groups were both included in the range of the criteria for radioiodine ablation therapy. Also, 2 hours and 24 hours radioiodine consumption measured after 4-week restrictive diet did not show statistical differences between two groups., Conclusion: A 2-week RID can be considered as a type of radioiodine ablation therapy after patients undergo a total thyroidectomy.

A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers, as well as novel therapeutic targets.

Purpose: Decision to perform concurrent ipsilateral thyroidectomy on patients with hypopharyngeal cancer is important, and unnecessary thyroidectomy should be avoided if oncologically feasible. We hypothesized that concurrent ipsilateral thyroidectomy is not routinely required to prevent occult metastasis. This study aimed to determine the prevalence of histological thyroid invasion in patients with hypopharyngeal cancer, and to refine the indications for prophylactic ipsilateral thyroidectomy in patients with hypopharyngeal cancer., Materials and Methods: A retrospective review of the medical records from the Department of Otolaryngology at Yonsei University College of Medicine was conducted from January 1994 to December 2009. A total of 49 patients underwent laryngopharyngectomy with thyroidectomy as a primary treatment of hypopharyngeal cancer., Results: The incidence of thyroid gland involvement was 10.2%. The most common route of invasion was direct extension through the thyroid cartilage. Thyroid cartilage invasion (p=0.034) was the most significant factor associated with thyroid invasion. Disease-specific survival at 5 years was lower in patients with than without thyroid gland invasion (26.7% vs. 55.2%, respectively; p=0.032). Disease-free survival at 5 years was also lower in patients with than without thyroid gland invasion (20.0% vs. 52.1%, respectively; p=0.024)., Conclusion: Ipsilateral thyroidectomy in combination with total laryngopharyngectomy is indicated when invasion of the thyroid cartilage is suspected in patients with hypopharyngeal cancer.

Kinase suppressor of RAS1 (KSR1) is a scaffold protein implicated in RAS-mediated RAF activation. However, the molecular function of KSR in papillary thyroid cancer (PTC) is unknown. Thus, this study aimed to characterize the role of KSR1 in patients with PTC. qRT-PCR and immunohistochemistry (IHC) revealed inter-tumor heterogeneities in the expression of KSR1 in PTC tissues. Interestingly, BRAFV600E-positive PTC showed higher KSR1 mRNA expression than BRAFV600E-negative PTC (P<0.001). Gene Set Enrichment Analysis (GSEA) using public repositories showed that high KSR1 expression coordinately upregulated Notch signaling (nominal P=0.019, false discovery rate (FDR) q-value=0.165); this finding was supported by GeneNetwork analysis, indicating that KSR1 expression is positively correlated with NOTCH1 expression (ρ=0.677, P=6.15×10(-9)). siRNA against KSR1 (siKSR1) significantly decreased ERK phosphorylation induced by BRAFV600E, resulting in reduced expression of NOTCH1 and HES1, targets of Notch signaling. GSEA revealed that high KSR1 expression was also associated with downregulation of genes related to oxidative phosphorylation (OxPhos). Consistent with this, electron microscopy showed that PTCs with high KSR1 expression exhibited structural defects of the mitochondrial cristae. Furthermore, siKSR1-transfected BCPAP and 8505C cells generated fewer colonies in colony-forming assays. In addition, GSEA showed that high expression of KSR2 and connector enhancer of KSR1 (CNKSR1) also coordinately upregulated Notch signaling (KSR2: nominal P=0.0097, FDR q-value=0.154 and CNKSR1: nominal P<0.0001, FDR q-value=0.00554), and high CNKSR2 was associated with downregulation of the OxPhos gene set (nominal P<0.0001, FDR q-value <0.0001). In conclusion, KSR1 is coordinately regulated with Notch signaling and OxPhos in PTC, because its scaffold function might be required to sustain the proliferative signaling and metabolic remodeling associated with this type of cancer., (© 2015 Society for Endocrinology.)

Aberrant expression of Cancer Osaka Thyroid Oncogene mitogen-activated protein kinase kinase kinase 8 (COT) (MAP3K8) is a driver of resistance to B-RAF inhibition. However, the de novo expression and clinical implications of COT in papillary thyroid cancer (PTC) have not been investigated.The aim of this study is to investigate the expression of A-, B-, C-RAF, and COT in PTC (n = 167) and analyze the clinical implications of aberrant expression of these genes.Quantitative polymerase chain reaction (qPCR) and immunohistochemical staining (IHC) were performed on primary thyroid cancers. Expression of COT was compared with clinicopathological characteristics including recurrence-free survival. Datasets from public repository (NCBI) were subjected to Gene Set Enrichment Analysis (GSEA).qPCR data showed that the relative mRNA expression of A-, B-, C-RAF and COT of PTC were higher than normal tissues (all P < 0.01). In addition, the expression of COT mRNA in PTC showed positive correlation with A- (r = 0.4083, P < 0.001), B- (r = 0.2773, P = 0.0003), and C-RAF (r = 0.5954, P < 0.001). The mRNA expressions of A-, B,- and C-RAF were also correlated with each other (all P < 0.001). In IHC, the staining intensities of B-RAF and COT were higher in PTC than in normal tissue (P < 0.001). Interestingly, moderate-to-strong staining intensities of B-RAF and COT were more frequent in B-RAF-positive PTC (P < 0.001, P = 0.013, respectively). In addition, aberrant expression of COT was related to old age at initial diagnosis (P = 0.045) and higher recurrence rate (P = 0.025). In multivariate analysis, tumor recurrence was persistently associated with moderate-to-strong staining of COT after adjusting for age, sex, extrathyroidal extension, multifocality, T-stage, N-stage, TNM stage, and B-RAF mutation (odds ratio, 4.662; 95% confidence interval 1.066 - 21.609; P = 0.045). Moreover, moderate-to-strong COT expression in PTC was associated with shorter recurrence-free survival (mean follow-up duration, 14.2 ± 4.1 years; P = 0.0403). GSEA indicated that gene sets related to B-RAF-RAS (P < 0.0001, false discovery rate [FDR] q-value = 0.000) and thyroid differentiation (P = 0.048, FDR q-value = 0.05) scores were enriched in lower COT expression group and gene sets such as T-cell receptor signaling pathway and Toll-like receptor signaling pathway are coordinately upregulated in higher COT expression group (both, P < 0.0001, FDR q-value = 0.000).Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC.

Background: Tumor multifocality is frequently observed in papillary thyroid carcinoma (PTC), but its prognostic value is controversial. We investigated the prognostic significance of multifocality in PTCs larger than 1 cm and papillary thyroid microcarcinomas (PTMC)., Methods: Medical records and pathologic results of 2,309 patients who received thyroidectomy and lymph node dissection for PTC were retrospectively reviewed. We identified 648 patients who had PTC with a primary tumor exceeding 1 cm, and 1,661 patients with PTMC. In each group, we compared patients with unifocal and multifocal disease. Cox regression analyses of disease persistence and recurrence were performed to identify the prognostic significance of multifocality., Results: The mean follow-up period was 5.6 years. In the analyses of PTCs larger than 1 cm, the multifocal group included more extensive thyroid surgeries (p = 0.039), radioactive iodine therapies with higher doses (p < 0.001), and significantly higher rates of disease persistence and recurrence (p = 0.001) compared with the unifocal group. In analogous analyses of patients with PTMC, disease persistence and recurrence did not differ significantly between the unifocal and multifocal groups. Cox regression analyses indicated that multifocality was an independent risk factor for disease persistence and recurrence in patients who had PTC with a tumor exceeding 1 cm, but not in patients with PTMC., Conclusion: Tumor multifocality appears to be an important prognostic factor for PTCs larger than 1 cm, but may have little or no prognostic significance for PTMC.

Metabolic reprogramming has been regarded as an essential component of malignant transformation. However, the clinical significance of metabolic heterogeneity remains poorly characterized. The aim of this study was to characterize metabolic heterogeneity in thyroid cancers via the analysis of the expression of mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative phosphorylation (OxPhos), and investigate potential prognostic correlations. Gene set enrichment analysis (GSEA) verified by reverse transcription polymerase chain reaction and gene network analysis was performed using public repository data. Cross-sectional observational study was conducted to classify papillary thyroid cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to investigate the clinicopathological features. GSEA clearly showed that the expression of OxPhos and MRP gene sets was significantly lower in primary thyroid cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid tumors (16.3%) in the public repository did not show a reduction in OxPhos mRNA expression. Remarkably, strong positive correlations between MRPL44 expression and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 α subcomplex, 5; succinate dehydrogenase complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5 (MRPS5) (P < 0.0001) were clearly denoted, suggesting that MRPL44 is a representative marker of OxPhos and MRP expressions. In laboratory experiments, metabolic heterogeneity in oxygen consumption, extracellular acidification rates (ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP, TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to OxPhos amount defined by expression of MRPL44 mRNA was significantly related to lymph node metastasis (LNM) (P < 0.001). Furthermore, multivariate analysis clearly indicated that expression of MRPL44 is associated with an increased risk of lateral neck LNM (odds ratio 9.267, 95% confidence interval 1.852-46.371, P = 0.007). MRPL44 expression may be a representative marker of metabolic phenotype according to OxPhos amount and a useful predictor of LNM.

Background: The purpose of this study was to examine whether the time required for recovery from transient hypoparathyroidism is correlated with the onset of hypocalcemic symptoms in patients with total thyroidectomy., Methods: Medical records of 54 patients were retrospectively reviewed. The correlation between the onset of hypocalcemic symptoms and the recovery time were compared for all patients divided into 3 groups based on first appearance of hypocalcemic symptoms; group 1, onset within 24 hours; group 2, onset at 24 to 48 hours; and group 3, onset >48 hours., Results: There was a negative correlation between onset and recovery times (p < .001). Serum parathyroid hormone levels 1 year after surgery were significantly lower in group 1 than in groups 2 or 3 (p < .001)., Conclusion: Recovery time can be predicted by time of onset of hypocalcemic symptoms and signs. Earlier onset leads to longer recovery times., (© 2014 Wiley Periodicals, Inc.)

Purpose: In 2001, the authors developed a novel method of gasless transaxillary endoscopic thyroidectomy (ET) and have now performed >1000 operations. This review was performed to document surgical outcomes after 10 years of experience with this technique and to determine what the role of ET has in the current era., Patients and Methods: All patients who underwent elective ET using the gasless transaxillary approach from November 2001 to December 2010 were evaluated. Patient demographics, surgical data, histologic analysis results, and complications were recorded and analyzed., Results: A total of 1085 patients underwent ET during the study period. Mean patient age was 36.9±9.7 years; the gender ratio was 1:49 (male:female). There were 228 benign thyroid tumor cases and 857 thyroid malignancies. Trend analysis showed a progressive increase in case numbers per month until the end of 2007, followed by a steady decline. There were 175 total thyroidectomy cases and 910 cases of less-than-total thyroidectomy. Mean overall operating time was 132.92±48.6 minutes, and the overall complication rate was 13.5%. The most common complications were: transient hypocalcemia (6.3%), transient hoarseness (3.9%), hematoma (0.4%), permanent hypocalcemia (0.1%), and permanent recurrent laryngeal nerve injury (0.2%)., Conclusions: Gasless ET is comparable to open thyroidectomy in terms of early surgical outcomes and complications, and it bridges the gap between conventional open surgery and robotic transaxillary thyroidectomy.

Despite the favorable therapeutic outcomes reported in differentiated thyroid cancer (DTC), a significant proportion of DTC patients present with refractory behavior to conventional therapy. The sirtuin (Sirt) family has recently been implicated in the maintenance of cellular homeostasis under genotoxic stress. Here, we investigated the induction of Sirt1 expression by etoposide-induced genotoxic stress to gain insights into thyroid carcinogenesis and identify novel therapeutic targets. Immunohistochemical staining analyses of Sirt1 and Sirt3 were performed using human thyroid cancer tissues and matched normal tissues, and bioinformatic analyses were done using public repositories, including the Human Protein Atlas, BioGPS, NCBI Gene Expression Omnibus (GEO) profiles, and GeneNetwork. TPC1, FTC133 and FRO cells were used for molecular biological experiments including apoptosis assays, MTT, immunofluorescence staining and qRT-PCR assays. The IHC data and public repositories data consistently showed variable Sirt1 and Sirt3 expression patterns in normal thyroid follicular cells and papillary thyroid cancer cells. The induction of Sirt1 and Sirt3 was cell type-specific and the expression levels of these genes correlated with apoptotic cell death and cell viability after etoposide-induced genotoxic stress. Sirt1‑Foxp3 signaling-mediated regulation of Bax and p21 mRNA expression was a signature molecular event in TPC1 cells, which showed remarkable resistance to etoposide-induced genotoxic stress. The induction of Sirt1 and Sirt3 may be a determinant of thyroid cancer cell survival under genotoxic stress conditions. Further examination of the Sirt1-Foxp3 signal may improve our understanding of thyroid carcinogenesis and help identify new druggable targets.

Introduction: Transaxillary robotic thyroidectomy is considered a technically feasible and safe treatment option for patients with low-risk papillary thyroid carcinoma (PTC). The aim of the present study was to determine the factors that contribute to the perioperative surgical outcomes of robotic thyroidectomy and to suggest guidelines for patient selection to be used by surgeons inexperienced in the technique., Method: We reviewed the records of 275 patients with PTC who underwent robotic total thyroidectomy using a gasless, transaxillary single-incision approach at Yonsei University Health System, South Korea, between January 2011 and May 2012. The association between surgical outcomes and clinicopathologic factors was assessed using linear and logistic regression analysis., Results: The contributing factors for surgical outcomes of robotic thyroidectomy were categorized as patient factors, including gender and body mass index (BMI), and thyroid-specific factors, including thyroid gland size, coexistent thyroiditis, tumor size, and serum anti-thyroglobulin antibody and anti-microsomal antibody titers. Of these, male gender, a large thyroid gland, and thyroiditis significantly increased the total operation time. Male gender, thyroiditis, and overweight BMI increased the working space time, and a large thyroid gland and overweight BMI affected the console time. A large thyroid gland and histological thyroiditis were associated with increased intraoperative blood loss. There was no association between postoperative complications and clinicopathologic parameters., Conclusion: Male gender, overweight BMI, a large thyroid gland, and coexistent thyroiditis adversely affected the surgical outcome of robotic thyroidectomy. Surgeons inexperienced in the technique should avoid or carefully approach individuals with these factors.

Background: Robotic thyroidectomy (RT), a new gasless, transaxillary approach developed by the Yonsei University group in Seoul, Korea, eliminates the need for a cervical incision. Since RT is technically complex and has a steep learning curve, the surgical complication rate may initially be higher than with conventional surgery. This study evaluated the complication rates of transaxillary RT and assessed ways to prevent surgical complications., Methods: Between October 2007 and March 2013, 3,000 patients underwent RT for thyroid cancer in the Department of Surgery, Yonsei University College of Medicine at Severance Hospital, Seoul. The medical records of these patients were reviewed retrospectively, and surgical complications were assessed on the basis of clinical findings., Results: The most common surgical complication was symptomatic hypocalcemia, of which 37.43 % cases were transient and 1.10 % permanent. Other surgical complications included recurrent laryngeal nerve injury (1.23 % transient, 0.27 % permanent), seroma (1.73 %), hematoma (0.37 %), chyle leakage (0.37 %), trachea injury (0.2 %), Horner's syndrome (0.03 %), carotid artery injury (0.03 %), and brachiocephalic vein injury (0.03 %). The technique-related complications, which were never seen in conventional open thyroidectomy, were axillary skin flap perforation (0.1 %), and traction injury of the arm on the side the lesion was located (0.13 %)., Conclusions: Surgeons who have mastered standardized robotic surgical procedures and who understand potential complications and how to prevent them can perform RT safely.

Background: Body image is associated with self-esteem and identity and has a close relationship with quality of life (QoL). We compared the impact of surgical scars on the patient's perception of body image between conventional open thyroidectomy (OT) and robotic thyroidectomy (RT) in female papillary thyroid carcinoma patients., Methods: From October 2009 to December 2010, we enrolled prospectively 116 papillary thyroid carcinoma patients who underwent total thyroidectomy at the Yonsei University Health System (Seoul, Korea). Of these 116 patients, 56 had OT and 60 RT. Their scars were assessed using the Vancouver Scar Scale (VSS), and psychometric properties were evaluated using the Body Image Scale (BIS) questionnaire postoperatively. Both groups were compared using cross-sectional and time-series methods., Results: Mean age was significantly younger in the RT group. Regarding scar quality, the OT group showed superiority in scar pigmentation and the total VSS score during the early postoperative period, but the VSS score improved over time and was similar between both groups at 9 months. The RT group had better scores regarding most of the BIS items, a trend that remained relatively constant over time. In patients with noticeable scars (VSS ≥ 2) at 9 months, the RT group had better BIS scores regarding almost all items, including "self-conscious," "physical attractiveness," "feeling of less feminine," "sexual attractiveness," "dissatisfaction with body, scar and appearance when dressed," and "avoidance of people due to appearance.", Conclusion: RT provides a better self-body image and improves QoL compared with conventional OT by avoiding a noticeable cervical scar., (Copyright © 2014 Mosby, Inc. All rights reserved.)