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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.)

Telomerase reverse transcriptase (TERT) promoter mutation has been investigated for its clinical and prognostic significance in aggressive papillary thyroid cancer (PTC). In this study, we aimed to assess the prevalence, clinicopathologic features, and treatment outcomes of TERT mutation-positive PTCs along with the common BRAF V600E mutation. We performed mutational analyses for BRAF and the TERT promoter in thyroid cancer patients who had undergone surgery at our institution since 2019. We reviewed and analyzed 7797 patients with PTC in this study. The prevalence of BRAF V600E and TERT promoter mutations was 84.0% and 1.1%, respectively. Multifocal gene mutations in bilateral PTCs were identified. TERT promoter mutations were associated with older age, larger tumor size, tumor multifocality, tumor variants, advanced stages, more adjuvant radioactive iodine treatment (RAI), higher stimulated serum thyroglobulin level before RAI, and more uptakes in the regions outside the surgical field on a post-RAI whole-body scan. The coexistence of BRAF V600E and TERT promoter mutations exacerbated all clinicopathologic characteristics. The frequency of TERT promoter mutations was the lowest in this study, compared to previous studies. TERT promoter mutations consistently correlated with aggressive PTCs, and the synergistic effect of both mutations was evident. Specific clinical settings in our institution and in Korea may have led to these distinctive results. Prospective multicenter studies with longer follow-up periods are required to establish valuable oncologic outcomes.

Background: It is difficult to reliably distinguish between American Thyroid Association (ATA) low-risk and intermediate-risk differentiated thyroid cancer (DTC) before surgery. Therefore, physicians are faced with a dilemma regarding the necessity and timing of completion total thyroidectomy (CT) after thyroid lobectomy (TL). We evaluated proper surgical methods by analyzing oncologic outcomes of TL in patients with DTC whose risk had been upgraded after surgery., Methods: We retrospectively reviewed the medical records of 1,702 patients with DTC who underwent TL and ipsilateral central lymph node (LN) dissection between January 2006 and December 2011. The patients were classified into Group A (n=1,159; low risk; ≤5 central LN metastases or the absence of pathologic microscopic capsular invasion) and Group B (n=543; upgraded intermediate risk after surgery; >5 central LN metastases or the presence of pathologic microscopic capsular invasion). We analyzed their clinicopathological characteristics and recurrence-free survival., Results: All 32 patients who experienced recurrence underwent CT. After the first operation, the duration until reoperation in Groups A and B were 8.00±2.74 (range, 3.42-12.17) and 5.10±3.09 (range, 1.25-11.67) years, respectively. There was no significant difference in recurrence rates, disease-related mortality rates, or 10-year recurrence-free survival rates between the two groups. The mean follow-up durations in Groups A and B were 10.22±1.58 and 10.13±1.47 years, respectively. Univariate analysis showed that sex, age, tumor size, multifocality, extrathyroidal extension (ETE), and number of central LN metastases were not associated with recurrence after TL, although the rate of central LN metastases was. Multivariate analysis showed that sex, age, tumor size, multifocality, ETE, central LN metastases, and the number of central LN metastases were not associated with recurrence after TL, although multifocality was., Conclusions: TL with prophylactic central compartment neck dissection (CCND) is sufficient for patients with DTC whose risk is upgraded after surgery because they have a good prognosis at long-term follow-up. Larger-scale randomized clinical trials are required to confirm our findings., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-158/coif). The authors have no conflicts of interest to declare., (2022 Gland Surgery. All rights reserved.)

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).)

Purpose: The surgical success rate for primary hyperparathyroidism (PHPT) is currently 95%-98%. However, 3%-24% of patients show persistently elevated (Pe) parathyroid hormone (PTH) levels after parathyroidectomy (PTX). This single-center retrospective study aimed to compare the outcomes of patients with normal PTH and PePTH levels after successful PTX and to identify the factors associated with PePTH., Methods: The normal group, defined as patients with normal serum calcium and PTH levels immediately after PTX, was compared with the PePTH group (patients with normal or low serum calcium and increased serum PTH levels up to 6 months postoperatively) to determine the causes of disease in the PePTH group., Results: There were no significant differences in age, sex, or preoperative estimated glomerular filtration rate between the normal PTH group (333 of 364, 91.5%) and the PePTH group (31 of 364, 8.5%). However, there were significant differences in preoperative 25-hydroxyvitamin D (17.9 and 11.8 ng/mL, respectively; P = 0.003) and PTH levels (125.5 and 212.4 pg/mL, respectively; P < 0.001) between the 2 groups. Among the 31 cases of the PePTH group, 18 were attributed to vitamin D deficiency., Conclusion: Preoperative vitamin D deficiency is a predictive factor for PePTH. Therefore, preoperative administration of vitamin D supplements may reduce the probability of postoperative disease persistence. Patients with temporary laboratory abnormalities within 6 months after successful PTX should be monitored, and appropriate vitamin D and calcium supplementation may reduce the effort and cost of various examinations or reoperations., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2022, the Korean Surgical Society.)

The diagnostic and treatment rates of early thyroid cancer have been increasing, including those of aggressive variants of papillary thyroid cancer (AVPTC). This study aimed to analyze the need for completion total thyroidectomy after lobectomy for clinically low-to-intermediate-risk AVPTC. Overall, 249 patients who underwent hemithyroidectomy (HT, n = 46) or bilateral total thyroidectomy (BTT, n = 203) for AVPTC between November 2005 and December 2019 at our single institution were examined. The average follow-up period was 14.9 years, with a recurrence rate of 4.3% and 10.8% in the HT and BTT groups, respectively. Multivariate Cox analysis revealed that palpable tumor on the neck during evaluation (HR, 2.7; 95% CI, 1.1-6.4; p = 0.025), clinical N1b (HR, 8.3; 95% CI, 1.1-63.4; p = 0.041), tumor size (cm) (HR, 1.3; 95% CI, 1.0-1.7; p = 0.036), gross extrathyroidal extension (HR, 3.1; 95% CI, 1.4-7.0; p = 0.007), and pathologic T3b (HR, 3.4; 95% CI, 1.0-11.4; p = 0.045) or T4a (HR, 6.0; 95% CI, 1.9-18.8; p = 0.002) were associated with an increased risk of recurrence. Incidentalomas identified during diagnosis had a significantly lower risk of recurrence (HR, 0.4; 95% CI, 0.2-0.9; p = 0.033). Close follow-up may be performed without completion total thyroidectomy for AVPTC found incidentally after HT.

Background: Laparoscopic adrenalectomy is the gold standard for adrenal tumor; however, robotic adrenal surgery has gained interest recently. For minimally invasive surgeries, we first reported on robotic adrenalectomy using a single-port access performed using the da Vinci multi-arm robotic system (RA-SA) in 2011. Since its introduction in 2018, we first performed robotic adrenalectomy using the da Vinci SP robotic system in 2020., Objective: We aimed to introduce the novel single-port robotic system (RA-SP) for adrenalectomy and evaluate its technical feasibility by comparing it with the surgical outcomes of patients who underwent robotic adrenalectomy using the RA-SA., Methods: Eight patients who underwent robotic adrenalectomy using the RA-SP from February 2020 to June 2021 were compared with 11 patients who underwent RA-SA from 2011 to 2015 by a single surgeon., Results: The two groups were similar in age, sex, body mass index, type of operation, and final pathologic diagnosis. Despite no significant differences, RA-SP resulted in moderately less mean operation time, estimated blood loss, and length of hospitalization., Conclusions: The Da Vinci SP robotic system is a novel, safe, and feasible technique to improve the convenience of operation and cosmetic effect for adrenalectomy., (© 2021. Society of Surgical Oncology.)

Background: Despite the increase in experience and understanding of robotic thyroidectomy, its application for Graves' disease (GD) remains controversial. This study aimed to assess the safety and feasibility of robotic transaxillary thyroidectomy (RTT) for GD in comparison with the conventional open thyroidectomy (open group: OG) approach., Methods: A total of 192 patients who underwent surgical resection for GD were retrospectively reviewed. Among them, 51 patients underwent RTT and the remaining 141 patients were in the conventional OG., Results: All robotic operations were performed successfully without open conversion. Patients who underwent RTT were significantly younger (P < 0.001) and predominantly of the female sex. Operative time was longer for RTT than for the OG (182.5 ± 58.1 vs. 112.0 ± 29.5; P < 0.001). The mean intraoperative blood loss was not statistically different between RTT and the OG (113.3 ± 161.6 vs. 95.3 ± 209.1, P = 0.223). The mean weight of the resected thyroid was reduced in those who underwent RTT compared with open thyroidectomy (P = 0.033). The overall complication rate for RTT and open thyroidectomy was not significantly different (33.3% vs. 22.7%, P = 0.135). In RTT, the most common complication was transient hypocalcemia (21%). Permanent hypocalcemia and recurrent laryngeal nerve injury occurred in only one patient in each group. The weight of the resected thyroid was not related to the incidence of complications in patients receiving RTT., Conclusions: Considering excellent cosmesis, findings of this study support the safety and feasibility of RTT. Nevertheless, it should be performed by expert surgeons with extensive robotic surgery experience., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Preoperative localisation studies are essential for parathyroidectomy in patients with primary hyperparathyroidism. If the location of abnormal parathyroid glands cannot be identified through non-invasive studies, parathyroid venous sampling (PVS) may be employed. In this study, we evaluated the utility of preoperative PVS in parathyroid surgery. Patients with primary hyperparathyroidism who underwent preoperative PVS at Severance Hospital between January 2015 and June 2020 were identified. Patients for whom the results of non-invasive imaging studies were inconsistent or negative underwent PVS. The results of PVS were compared with operative findings and pathologic results. For 14 patients, the results of preoperative ultrasonography and 99m Tc-sestamibi single-photon emission computed tomography (SPECT) were negative; for 20 patients, either the result of only one test was positive, or the results of the two tests were inconsistent. With respect to the lateralisation of diseased adenoma, the results of PVS and pathological examination were inconsistent only for one patient in either group (total: 2/34 patients). This study showed that PVS could be used effectively for preoperative localisation in patients with primary hyperparathyroidism in whom the location of diseased parathyroid glands cannot be determined through non-invasive image studies., (© 2022. The Author(s).)

Background: Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients., Methods: A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122)., Results: NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025); nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group ( P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions ( P = 0.004) that were smaller ( P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions., Conclusion: We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic. Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

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: Pediatric patients with differentiated thyroid cancer (DTC) present with unique characteristics compared to adult patients. This study aimed to evaluate clinical presentation and surgical outcomes according to age and to identify the clinical significance of age in DTC., Methods: In total, 98 pediatric patients, 1261 young adult patients, and 4017 adult patients with DTC who underwent thyroid surgery between January 1982 and December 2012 at Yonsei University Hospital (Seoul, Republic of Korea) were retrospectively reviewed. The mean follow-up duration was 120.4 ± 54.2 months., Results: Mean tumor size was significantly larger in the pediatric group than in the adult groups ( p < 0.001). The recurrence rate was significantly higher in the pediatric group (14.3% versus 6.6% versus 3.0%, p =0.004 and p < 0.001). In multivariate analysis, the risk of disease-free survival (DFS) was lower in the adult group (HR, 0.362; p < 0.001). Reanalysis of patients with tumor size of 2-4 cm revealed that the adult group was not a significant risk factor for DFS in multivariate analysis (HR, 0.305; 95% CI, 0.158 to 0.588; p < 0.001)., Conclusions: Our findings suggest that pediatric patients present with more aggressive features and higher recurrence rates compared to adult patients and should be carefully treated from initial evaluation to surgery and postoperative care., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Kwangsoon Kim et al.)

Background: The posterior retroperitoneoscopic approach (PRA) has been under attention as a method for resection of paraganglioma (PGL) for the past few years. However, only a few studies have explored the effectiveness and safety of the PRA for aortocaval and infrarenal PGL resection., Methods: We designed this retrospective study to investigate the safety and effectiveness of the PRA for aortocaval and infrarenal PGL resection in a single center. We retrospectively reviewed the medical records of patients who underwent PRA for PGL resection at our medical center from January 2006 to March 2021. Eight patients were enrolled, of whom six had aortocaval PGL. We investigated the surgical outcomes of enrolled patients., Results: The locations of the tumors in relation to the renal vein were: suprarenal in two (25.0%) patients, at the renal vein level in three (37.5%) patients, and infrarenal in three (37.5%) patients. The mean operative time of the enrolled patients was 101.5 ± 39.1 min. The mean postoperative stay was 3.5 ± 1.5 days, and the estimated blood loss was 31.3 ± 51.4 ml. There was one minor complication (chyle leakage), and two hypotensive events occurred during the surgery. Focusing on the results of the renal vein level and infrarenal PGL resection, the mean operative time, mean postoperative stay, and estimated blood loss of the patients were 109.2 ± 41.3 min, 3.5 ± 1.8 days, and 41.7 ± 56.4 ml, respectively., Conclusion: The PRA for aortocaval and infrarenal PGL resection is feasible and safe. Additional data analysis and long-term follow-up are needed in the future., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Due to the paucity of data and controversy regarding the preferred surgical approach for managing tertiary HPT, we sought to investigate the outcomes of different surgical approaches in managing this challenging disease., Methods: We performed a multi-center retrospective study to include patients with tertiary HPT who underwent STPX or total parathyroidectomy with autotransplantation (TPX-A)., Results: One hundred five patients had kidney transplant, and 43 were on dialysis. In the kidney transplant group, 61 patients underwent STPX, and 44 for TPX-A. Patients' demographics were not significantly different (48.61 ± 9.31 vs 47.95 ± 12.73 years, P = 0.759. The postoperative follow-up showed that the TPX-A cohort had a higher rate of hypoparathyroidism (N = 20, 45.45%) versus (N = 14, 22.95%) with the STPX cohort (P = 0.013). The cure among the TPX-A cohorts (84.09%) over the STPX cohort (73.77%) (P = 0.153). The long-term follow-up showed that the rate of developing temporary (N = 16, 41.03%) or permanent (N = 8, 20.51%) hypoparathyroidism was significantly higher among patients who underwent TPX-A over the patients who underwent STPX (N = 7, 17.95%), and (N = 4, 10.26%), respectively (P = 0.012). There was no statistical difference between the persistence (N = 3, 7.69%) or the recurrence (N = 2, 5.13%) of the HPT in the TPX-A cohort and the STPX cohort (N = 2, 5.13%). (N = 4, 10.26%), respectively, P = 0.644., Conclusions: To our knowledge, this is the largest multi-center study that compared different approaches for managing tertiary HPT. Showing that STPX is the better modality in patients diagnosed with tertiary HPT and had kidney transplants avoiding the risk of hypoparathyroidism., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The most common genetic backgrounds of hereditary paraganglioma and pheochromocytoma (PPGL) are SDHx germline mutations. Given the fact that the immunohistochemistry (IHC) result for SDHB is always negative regardless of the type of SDHx mutation, we aimed to evaluate the efficacy of using SDHB IHC for screening SDHx mutations in PPGL cases. In total, 52 patients who underwent surgery for PPGL treatment between 2006 and 2020 and underwent genetic analysis at diagnosis were included. Tissue microarrays (TMAs) were constructed with PPGL tissues and IHC for SDHB was performed on TMA sections. All 10 patients with SDHB-negative IHC contained SDHB or SDHD mutations. The genetic test results of patients with SDHB-weakly positive IHC varied (one SDHB , two RET , one VHL , and three unknown gene mutations). There were no SDHx mutations in the SDHB-positive IHC group. Six patients with weakly positive SDHB IHC with primarily unknown genetic status were re-called and underwent next-generation sequencing. None of them had SDHx mutations. In conclusion, SDHB-negative IHC is a cost-effective and reliable method to predict SDHx mutations. However, in the case of weakly positive SDHB staining, an additional gene study should be considered.

Background: Laparoscopic adrenalectomy is widely used for treating various adrenal tumors. Posterior retroperitoneoscopic adrenalectomy was introduced after transperitoneal laparoscopic adrenalectomy. The comparability and superiority of posterior retroperitoneoscopic adrenalectomy have been widely investigated. We aimed to compare the outcomes of posterior retroperitoneoscopic adrenalectomy and transperitoneal laparoscopic adrenalectomy using 10 years' data. The changes in outcomes over time were also analyzed., Methods: This was a retrospective observational study. A total of 505 patients who underwent laparoscopic adrenalectomy between 2009 and 2018 were included. The patients were divided into two groups: transperitoneal (n=114) and retroperitoneal (n=391) groups. Patients who underwent posterior retroperitoneoscopic adrenalectomy were further classified into sub-groups (sub-group 1: 2009-2012; sub-group 2: 2013-2015; and sub-group 3: 2016-2018) based on time periods. Clinicopathological factors and postoperative outcomes were retrospectively reviewed and analyzed., Results: The retroperitoneal group showed significantly shorter operation time, diet initiation time, and hospital stay compared to the transperitoneal group (P=0.000, 0.000 and 0.000, respectively). Analgesics were used less frequently in the retroperitoneal group than in the transperitoneal group (P=0.048). In the retroperitoneal group, the time to postoperative diet initiation shortened over time (P=0.000)., Conclusions: Posterior retroperitoneoscopic adrenalectomy is a favorable surgical method that results in patient outcomes that are comparable to those of conventional transperitoneal laparoscopic adrenalectomy, without compromising patient safety., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-178). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Thyroid cancer in children is very uncommon. For pediatric thyroid cancer, robotic surgery has served as a minimally invasive surgical alternative to conventional open surgery. Our study aimed to evaluate the results of robotic versus open surgical treatment for patients with thyroid cancer younger than 20 years of age at the time of diagnosis. This retrospective review included 161 pediatric patients who underwent robotic transaxillary or conventional open thyroidectomy at our institution from 2008 to 2019. Of these patients, 99 comprised the robotic group and 62 the open group. Patient demographics, surgical outcomes, and disease-free survival rates were compared between the two groups. Patients in the open group were more likely to have advanced stage diseases with a larger tumor size and higher tumor-node-metastasis stage than those in the robotic group. Operation time and follow-up period were similar in both groups. Patients in the robotic group had a lower rate of postoperative complications and a shorter length of hospital stay, but they also had a lower average number of retrieved central lymph nodes. However, there were no significant between group differences in recurrence rates and disease-free survival. In the hands of an experienced surgeon, robotic thyroidectomy is a feasible and safe option for pediatric patients.

Background: Postoperative transient hypocalcemia (TH) is a common complication of total thyroidectomy. This retrospective study evaluated the clinical utility of preoperative vitamin D3 injection for the prevention of TH after total thyroidectomy., Methods: We included 2294 patients who underwent total thyroidectomy from January 2015 until October 2018 and retrospectively analyzed their data by complete chart review at our hospital. The patients were divided into two groups: vitamin D3 injection (VDI; n  = 342) and vitamin D3 noninjection (VDN; n  = 1952). TH was defined as serum calcium <8.2 mg/dL and signs or symptoms of hypocalcemia., Results: The mean preoperative serum 25-hydroxyvitamin D (25-OHD) levels of the VDI group were significantly lower than those of the VDN group (16.5 ± 6.9 ng/mL vs 19.4 ± 8.7 ng/mL, p  < 0.001). Multivariate analysis indicated that the significant risk factors of TH include vitamin D noninjection (hazard ratio (HR): 1.717, 95% confidence interval (CI): 1.282-2.300, p  < 0.001), male gender (HR: 1.427, 95% CI: 1.117-1.822, p  = 0.004), and capsular extension (HR: 1.273, 95% CI: 1.011-1.603, p  = 0.040)., Conclusions: Preoperative vitamin D3 injection significantly contributed to the prevention of TH after total thyroidectomy. Further prospective or multicenter studies must be conducted to determine the effect of vitamin D3 injection., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Kwangsoon Kim et al.)

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.

Objectives/hypothesis: Papillary thyroid carcinoma (PTC) tends to metastasize rather early to local lymph nodes (LNs). Incidences of cystic LN metastases is relatively rare compared with that of solid LN metastases. Few studies have attempted to assess the characteristics in these patients. This study aimed to compare the clinicopathologic characteristics and surgical outcomes between patients with cystic LN metastases and those with solid LN metastases., Study Design: Retrospective cohort study., Methods: We retrospectively reviewed the data of 1,028 patients with N1b PTC who underwent bilateral total thyroidectomy with central compartment neck dissection and modified radical neck dissection between January 2005 and September 2011. Of these, 136 (13.2%) had cystic LN metastases and 892 (86.8%) had solid LN metastases. Clinicopathologic characteristics and surgical outcomes were compared between these two patient groups., Results: The proportion of patients with thyroid tumor multifocality was relatively higher in the cystic node cohort (19.9% vs. 12.7%, P = .048). The number of total metastatic LNs and positive lateral LNs was slightly higher in the cystic node cohort (11.3 ± 8.9 vs. 9.7 ± 7.5, P = .029 and 6.9 ± 6.3 vs. 5.5 ± 4.6, P = .018, respectively). The proportion of patients with recurrence was higher in the cystic node cohort (14.0% vs. 3.0%, P < .001). Multivariate analysis indicated that cystic nodes were a significant risk factor for recurrence (hazard ratio: 5.265, 95% confidence interval: 2.898-9.563)., Conclusions: This study demonstrates that cystic lateral LN metastases are associated with aggressive tumor behavior in PTC patients. and that their presence is a significant independent prognostic factor for disease-free survival., Level of Evidence: 2b Laryngoscope, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Paragangliomas (PGL) are rare neuroendocrine tumors derived from chromaffin cells of the autonomic nervous system. We aim to describe our experience and the long-term outcome of abdominal PGL over the last decade., Methods: A retrospective review of patients diagnosed with PGL in our hospital between November 2005 and June 2017 was conducted. All nonabdominal PGL were excluded and the clinicopathological features and long-term outcomes of the patients were analyzed., Results: A total of 46 patients were diagnosed with abdominal PGL. The average age of diagnosis was 55.4 years and there was no sex predilection. The average tumor size was 5.85 cm and they were predominantly located in the infrarenal position (50%). The mean follow-up period was 42 months (range, 1.8-252 months). All patients with metastases had Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) of ≥4. One patient presented with synchronous metastases while 2 developed local recurrence and distant metastases. One presented with only local recurrence. One patient died 5 years after diagnosis., Conclusion: Abdominal PGL is a rare tumor with excellent long-term prognosis. Recurrence although uncommon, can occur decades after initial diagnosis. Long-term follow-up is therefore recommended for all patients with PGL, especially in patients with PASS of ≥4., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2020, the Korean Surgical Society.)

The necessity of completion total thyroidectomy in patients with papillary thyroid microcarcinoma (PTMC) and pathological central lymph node metastasis (pCLNM) who underwent thyroid lobectomy with central compartment neck dissection (CCND) is unclear. We determined the necessity of completion total thyroidectomy by retrospectively comparing the prognosis according to the presence of pCLNM during a long-term follow-up. We enrolled 876 patients with PTMC who underwent thyroid lobectomy with prophylactic CCND from January 1986 to December 2009. Patients were divided according to central lymph node (CLN) metastasis: 165 (18.8%) and 711 (81.2%) in the CLN-positive and CLN-negative groups, respectively. Medical records were reviewed retrospectively, and clinicopathologic characteristics and recurrence rates were analyzed. The CLN-positive group was associated with male sex ( p = 0.001), larger tumor size ( p < 0.001), and more microscopic capsular invasion ( p < 0.001) compared with the CLN-negative group. There was no significant difference between the two groups' recurrence ( p = 0.133) or disease-free ( p = 0.065) survival rates. Univariate and multivariate analyses showed no factors associated with tumor recurrence except male sex (hazard ratio = 3.043, confidence interval 1.117-8.288, p = 0.030). Patients who were diagnosed with pCLNM after undergoing thyroid lobectomy with prophylactic CCND do not require completion total thyroidectomy; however, frequent follow-up is necessary for patients with PTMC and pCLNM., Competing Interests: The authors declare no conflict of interest.

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.

Background: Minimally invasive thyroidectomy (MIT) is a safe method of performing thyroidectomy with notable benefits, such as improved cosmesis and reduced postoperative pain. The objective of this retrospective study was to report our experience with the technical feasibility of MIT, and compare its early surgical outcomes with those of conventional open thyroidectomy (COT) in patients with differentiated thyroid carcinoma (DTC)., Methods: A total of 617 patients who underwent MIT and 2,674 patients who underwent COT were reviewed between March 2006 and November 2017 at Yonsei University (Seoul, Korea). The mean follow-up duration was 41.2±19.7 months., Results: The mean age of patients with DTC was 46.1±11.2 years. The mean operation time in the MIT group was significantly shorter than that of the COT group (63.5±26.2 vs. 85.3±36.8 minutes, P<0.001). The mean hospital stay was significantly shorter in the MIT group than it was in the COT group as well (2.7±0.6 vs. 3.1±0.8 days, P<0.001). There were significantly fewer painkillers used after surgery in the MIT group than in the COT group (1.2±0.5 vs. 2.7±1.6, P<0.001). The mean number of harvested LNs in the MIT group was significantly lower than that of the COT group (3.1±2.6 vs. 5.5±4.0, P<0.001)., Conclusions: This study demonstrated that MIT is technically feasible in patients with DTC. MIT is a valuable alternative operative technique to COT with good surgical outcomes and outstanding cosmetic results., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs-20-512). The authors have no conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

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.

Surgical excision is the preferred treatment for multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism (PHPT), although controversy regarding the surgical strategy exists. We retrospectively investigated the short-term outcomes of PHPT by various surgical extents. Thirty-three patients who underwent parathyroidectomy due to MEN1-related PHPT at Yonsei Severance Hospital between 2005 and 2018 were included (age [mean ± SD], 43.4 ± 14.1 [range, 23-81] years). Total parathyroidectomy with auto-transplantation to the forearm (TPX) was the most common surgical method (17/33), followed by less-than-subtotal parathyroidectomy (LPX; 12/33) and subtotal parathyroidectomy (SPX; 4/33). There was no postoperative persistent hyperparathyroidism. Recurrence was high in the LPX group without significance (1 in TPX, 2 in SPX, and 3 in LPX, p = 0.076). Permanent and transient hypoparathyroidism were more common in TPX (n = 6/17, 35.3%, p = 0.031; n = 4/17, 23.5%, p = 0.154, respectively). Parathyroid venous sampling (PVS) was introduced in 2013 for preoperative localisation of hyperparathyroidism at our hospital; nine among 19 patients operated on after 2013 underwent pre-parathyroidectomy PVS, with various surgical extents, and no permanent hypoparathyroidism (p = 0.033) or post-LPX recurrence was observed. Although TPX with auto-transplantation is the standard surgery for MEN1-related PHPT, surgical extent individualisation is necessary, given the postoperative hypoparathyroidism rate of TPX and feasibility of PVS.

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: The 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor-node-metastasis (TNM) staging system was released with major revisions. The purpose of this retrospective study was to investigate differences between the 7th and 8th editions of the AJCC/UICC TNM staging system and to compare the predictability of prognosis between the two staging systems with patients who underwent thyroidectomy for differentiated thyroid cancer (DTC) at a single institution., Methods: A total of 3238 patients underwent thyroid operation from January 2002 to December 2006 at Yonsei University Hospital (Seoul, Korea), of which 2294 with complete clinical data and sustained follow up were enrolled. Clinicopathologic features and TNM staging by applying the 7th and 8th editions of the AJCC/UICC were analyzed retrospectively by the complete review of medical charts and pathology reports of patients. Mean follow-up duration was 132.9 ± 27.9 months., Results: A significant number of T3 patients were downstaged to T1 (838, 36.5%) and T2 (122, 5.3%). After applying the 8th edition of the AJCC/UICC TNM staging system, the number of stage I patients increased significantly from 1434 (62.5%) to 2058 (89.7%), whereas numbers of stage III and IV patients decreased significantly from 644 (28.1%) to 33 (1.4%) and from 199 (8.7%) to 17 (0.7%), respectively. According to Kaplan-Meier survival analyses and values of the Harrell's c-index and integrated area under the curve (iAUC), the 8th edition has significantly better predictive performance for disease-free survival (DFS) and disease-specific survival (DSS) than the 7th edition., Conclusions: A significant population was downstaged after applying the 8th edition of the AJCC/UICC TNM staging system, and the 8th edition provided significantly better accuracy in predicting DFS and DSS in patients with DTC., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Hemodynamic stability is one of the most critical aspects of adrenal surgery for pheochromocytoma. Few articles have evaluated the hemodynamic status of patients undergoing posterior retroperitoneal adrenalectomy (PRA) for pheochromocytoma. The aim of this study is to compare the intraoperative hemodynamic parameters between lateral transperitoneal adrenalectomy (TPA) and PRA in this groups of patients.This report describes a retrospective study of 53 pheochromocytoma patients who underwent endoscopic adrenalectomy via transperitoneal (22 patients) or posterior retroperitoneal (31 patients) approaches from January 2008 to March 2015. Data from these patients were compared to investigate the differences in hemodynamic parameters between the 2 approaches.Clinical parameters at presentation were similar between the 2 groups, except for tumor size, which was larger in the TPA group. The PRA group is associated with reduced operative time, blood loss, and length of hospital stay compared to TPA even after adjusting for the tumor size. There was greater BP fluctuations and higher maximum systolic and diastolic blood pressure (BP) within the TPA group compared to PRA during univariate analysis. This was however not significant after adjusting for tumor size. There was no difference in the intraoperative inotropic support requirement between the 2 groups.PRA is associated with stable intraoperative hemodynamic status, as well as favorable perioperative outcomes compared to TPA in patients with small pheochromocytomas.

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.)

Parathyroidectomy (PTX) is the standard treatment for secondary hyperparathyroidism (SHPT); however, the administration of cinacalcet has gained prominence as a noninvasive treatment. We aimed to determine whether PTX or cinacalcet is more effective in preventing morbidity and mortality through reviewing follow-up data concerning surgical management of SHPT. We retrospectively analyzed and divided 209 patients with SHPT into two treatment groups: PTX (n = 78) and cinacalcet (n = 131) groups. We compared clinical features, the over-the-target range rate during pre- and post-intervention periods, new cardiovascular events, and all-cause mortality between both groups. Almost all biochemical parameters were well controlled in the post-intervention period, and were within the recommended target range for the PTX group but not for the cinacalcet group. A significant difference was observed in the over-the-target range rate during the post-intervention period between the groups. PTX and cinacalcet interventions significantly lowered the over-the-target range rates for serum intact parathyroid hormone (iPTH) (>300 pg/mL), corrected calcium (>10.5 mg/mL), serum phosphorus (>5.5 mg/dL), and calcium-phosphorus product (>55) in both groups (p = 0.001). PTX reduced the risk of new cardiovascular events by 86% compared to cinacalcet (p = 0.001); however, all-cause mortality did not differ significantly (14.1% vs. 7.6%, p = 0.132). For patients with SHPT, PTX helps prevent cardiovascular events through normalizing biochemical variables, according to recommended guidelines. PTX should be considered before cinacalcet treatment to prevent new cardiovascular events. Early PTX for appropriate patients can help prevent immediate postoperative complications and mortality.

Recently, the 2015 American Thyroid Association (ATA) risk stratification and the 8 th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system were released. This study was conducted to assess the clinical value of the lymph node ratio (LNR) as a predictor of recurrence when integrated with these newly released stratification systems, and to compare the predictive accuracy of the modified systems with that of the newly released systems. The optimal LNR threshold value for predicting papillary thyroid cancer (PTC) recurrence was 0.17857 using the Contal and O'Quigley method. The 8 th edition of the AJCC/UICC TNM staging system with the LNR and the 2015 ATA risk stratification system with the LNR were significant predictors of recurrence. Furthermore, calculation of the proportion of variance explained (PVE), the Akaike information criterion (AIC), Harrell's c index, and the incremental area under the curve (iAUC) revealed that the 8 th edition of the TNM staging system with the LNR, and the 2015 ATA risk stratification system with the LNR, showed the best predictive performance. Integration of the LNR with the TNM staging and the ATA risk stratification systems should improve prediction of recurrence in patients with PTC.

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.

Less-intense TSH suppression strategies can be used for differentiated thyroid cancer (DTC) patients with a low recurrence risk, but their metabolic outcomes are not well known. We aimed to evaluate changes in the serum cholesterol levels and the risk of hypercholesterolemia according to postoperative TSH levels in 1092 female DTC patients receiving levothyroxine after total thyroidectomy. The preoperative-to-follow-up change in total cholesterol (TC) levels in the TSH level <0.03, 0.03-0.3, 0.3-2, and 2-5 mIU/L groups was -3.69 mg/dL ( p = 0.006), +0.13 mg/dL ( p = 0.926), +12.46 mg/dL ( p < 0.001), and +16.46 mg/dL ( p < 0.001), respectively. When compared with TSH levels of 0.03-0.3 mIU/L, those of 0.3-2 mIU/L were found to be associated with hypercholesterolemia (adjusted odds ratio (AOR) = 1.86 and 5.08 for TC 200-240 and ≥240 vs. <200 mg/dL) and hyper-low-density lipoprotein (LDL)-cholesterolemia (AOR = 2.76 for LDL-cholesterol ≥160 vs. <130 mg/dL). Additionally, TSH levels of 2-5 mIU/dL were associated with hypercholesterolemia (AOR = 2.85 and 6.95 for TC 200-240 and ≥240 vs. <200 mg/dL) and hyper-LDL-cholesterolemia (AOR = 2.08 and 4.17 for LDL-cholesterol 130-159 and ≥160 mg/dL vs. <130 mg/dL). In patients with normal TSH level maintenance following thyroidectomy, TC levels markedly increased, resulting in an increased hypercholesterolemia prevalence. Metabolic derangement risk due to insufficient levothyroxine replacement should be considered in the adoption of less-intense TSH suppression strategies, postoperatively, in DTC patients.

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.

Obesity is associated with increased operating times and higher complication rates in many types of surgery. Its impact on robotic thyroidectomy however, is not well documented. The aim of this study was to investigate the relationship between body mass index (BMI) and robotic transaxillary thyroidectomy (RTAT). A retrospective review of prospectively collected data of all patients who underwent RTAT at Yonsei University Health System from October 2007 to December 2014 was performed. Patients were divided into three groups based on BMI (Group 1: BMI < 25, Group 2: BMI 25-29.99, Group 3: BMI ≥ 30), and compared. A total of 3697 patients were analyzed. No differences between the three groups were observed in clinicopathological factors, extent of surgery or length of stay. After multivariate analysis, only seroma and transient voice hoarseness were related to increasing BMI. Total operative time was significantly longer for Group 3 patients with less-than-bilateral total thyroidectomy (BTT), but was not significantly different for patients with BTT. Although obese patients undergoing RTAT have a slightly higher risk of seroma, transient voice hoarseness, and longer operative times, BMI did not influence the other important surgical outcomes of thyroidectomy. Therefore, obesity should not be a contraindication for performing RTAT.

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.

Purpose: Recently, posterior retroperitoneoscopic adrenalectomy (PRA) has been reported to have some advantages over laparoscopic transperitoneal adrenalectomy (LTA). The objectives of this study were to report our experience over 12 years with laparoscopic adrenalectomy for primary hyperaldosteronism (PHA) and to examine surgical outcomes of PRA compared with LTA in patients with PHA., Methods: The medical records of 527 patients who underwent minimally invasive adrenalectomy, including LTA or PRA, from January 2006 until May 2017 were reviewed at Severance Hospital (Seoul, Korea). Clinicopathologic characteristics and surgical outcomes of 146 patients with PHA who underwent LTA (19 patients) or PRA (127 patients) were analyzed retrospectively by complete chart review., Results: The overall rates of biochemical and clinical cure were 91.1% and 93.1%, respectively. The mean operation time of the PRA group was significantly shorter than that of the LTA group (72.3 ± 24.1 minutes vs . 115.7 ± 69.7 minutes, P = 0.015). The length of hospital stay in the PRA group was significantly shorter than in the LTA group (3.5 ± 1.3 days vs . 4.2 ± 1.6 days, P = 0.029), and the first meal after surgery came earlier in the PRA group (0.3 ± 0.5 days vs . 0.6 ± 0.5 days, P = 0.049). The number of pain-killers used was also significantly smaller in the PRA group (2.3 ± 2.1 vs . 4.3 ± 2.3, P < 0.001)., Conclusion: PRA offers an alternative or likely superior method for treatment of small adrenal diseases such as PHA, with improved surgical outcomes.

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.)

Robotic neck dissection (ND) for the thyroid cancer with lateral neck metastasis case is one of the emerging surgical techniques, and has been highlighted as minimally invasive surgical technique recently. Gasless, transaxillary robotic approach enabled the surgeon to do meticulous and precise dissection in the complex procedure, such as ND, eventually showed favorable surgical safety and outcomes, as well as superior functional and cosmetic benefits. In this article, the author would like to introduce the detailed techniques and secure evidences for the gasless, transaxillary robotic ND., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.