Null Association between BRAF V600E Mutation and Tumor Recurrence in Patients with Papillary Thyroid Microcarcinoma in South Korea

Background and Objectives@#The clinical implications of the BRAF V600E mutation in papillary thyroid microcarcinoma (PTMC), defined as ≤1.0 cm of tumor size, remain controversial. We investigated the association between the BRAFV600E mutation and PTMC recurrence in a retrospective cohort of patients with thyroid cancer. @*Materials and Methods@#This study included 2319 patients with PTMC (median age, 50 years [interquartile range (IQR), 41-57 years]) who underwent thyroid surgery from 2010 to 2019 at a single tertiary medical center. The median follow-up time was 75 months (IQR, 30-98 months). Tumor recurrence was confirmed by histological, cytological, radiographic, and biochemical criteria, combined with persistent and recurrent disease. @*Results@#A total of 60.2% (1395/2319) patients with PTMC had the BRAF V600E mutation. The tumor recurrence rate was 2.1% (19/924) in BRAF mutation-negative patients and 2.9% (41/1395) in BRAF mutation-positive patients, with a hazard ratio (HR) of 1.05 (95% confidence interval [CI], 0.61-1.84) after adjusting for clinicopathological risk factors. Similar results were found in patients with high-risk PTMC (adjusted HR, 1.09; 95% CI, 0.56-2.11) who had lymph node metastasis (LNM), extrathyroidal extension (ETE), or distant metastasis (DM) at diagnosis and in patients with low-risk PTMC (adjusted HR, 1.00; 95% CI, 0.35-2.83) who had no LNM, ETE, or DM. @*Conclusion@#The finding that the BRAF V600E mutation was not associated with tumor recurrence in our cohort of Korean patients with PTMC, especially in patients with low-risk PTMC, suggests that its value in the prediction of disease progression is limited.

Intraoperative Neuromonitoring during Thyroid Surgery

Intraoperative neuromonitoring is a well-established method used to prevent intraoperative nerve damage, and many studies have been performed in thyroid surgery. We introduced the basic concept and practical application of intraoperative neuromonitoring, as well as its standardized techniques and detailed contents. In addition, the contents of this still yet relatively unknown field, such as its application in transoral robotic thyroidectomy and its application to the external branches of the superior laryngeal nerve, were summarized by referring to many previous studies.

Intraoperative Neuromonitoring during Thyroid Surgery

Intraoperative neuromonitoring is a well-established method used to prevent intraoperative nerve damage, and many studies have been performed in thyroid surgery. We introduced the basic concept and practical application of intraoperative neuromonitoring, as well as its standardized techniques and detailed contents. In addition, the contents of this still yet relatively unknown field, such as its application in transoral robotic thyroidectomy and its application to the external branches of the superior laryngeal nerve, were summarized by referring to many previous studies.

Robotic transoral thyroidectomy for papillary thyroid carcinoma

Transoral robotic thyroidectomy (TORT) is well consistent with the primary goal of remote-access thyroid surgery, which is to avoid a visible cervical scar. Additionally, the extent of transoral thyroidectomy dissection is less than that of other remote-access surgical procedures. Owing to these merits of the transoral approach, several institutions around the world are now performing this procedure. Since transoral thyroidectomy is performed in a confined, narrow space, and is characterized by a close distance from the ports to the working space, more benefits can be derived from multiarticulation of robotic instruments. Especially when performing left lobectomy by TORT, the surgeon can use right-handed robotic instruments over the thyroid cartilage with the merits of multiarticulation. In this study, we present our unique procedure of left lobectomy by TORT in detail.

Transoral Robotic Thyroidectomy: The Overview and Suggestions for Future Research in New Minimally Invasive Thyroid Surgery

PURPOSE OF REVIEW: This journal introduces a overview in depth about the evolution of transoral robotic thyroidectomy, which has been encountering major confrontations in expanding its indications. RECENT FINDINGS: Transoral robotic thyroidectomy (TORT) is one of the newest approaches and draws attention because of its cosmetic excellence. The major advantage of TORT is comparatively smaller flap dissection area than other remote-access methods. The other advantage of TORT is that the wounds of lips fades out over time, and leaves concealed scar near axilla. SUMMARY: TORT can be done safely to the appropriately selected patients by surgeon expertise in robotic thyroidectomy. It might be a potential alternative surgical approach for thyroidectomy to surgeons who are experienced in remote-access robotic surgery.

Robotic Transoral Thyroidectomy: Right Thyroidectomy and Ipsilateral Central Neck Dissection with da Vinci Si Surgical System

Transoral approach for thyroidectomy recently gains a lot of attention among the thyroid surgeons, with the merits of cosmetic outcomes and minimal flap dissection. We've successfully introduced the robotic surgical system to the transoral approach for thyroidectomy. For transoral robotic thyroidectomy, we made 3 incisions in the gingival-buccal sulcus for three intraoral ports. An additional axilla port was inserted for counter-traction and later drain insertion. Herein, our unique procedures of transoral robotic thyroidectomy (TORT) are described in the treatment of a patient with papillary thyroid carcinoma.

Comparing the safety of harmonic ACE and ACE+ around the recurrent laryngeal nerve in swine models

PURPOSE: Among the various energy-based devices, ultrasonic shears are popular in thyroid surgeries. In this study, we tested the safety of Harmonic ACE and Harmonic ACE+ around the recurrent laryngeal nerve (RLN) in experimental swine models. METHODS: Harmonic ACE and Harmonic ACE+ were each tested in 4 piglets. Harmonic ACE and Harmonic ACE+ were activated at a 0- to 5-mm distance from the RLN. The function of the RLN was assessed using continuous electrophysiological monitoring. RESULTS: For Harmonic ACE, there was no adverse EMG event found when activated at 4- and 5-mm distances from the RLN. At a 2- to 3-mm distance, there were 4 adverse EMG events observed. In these 4 cases, adjacent tissue shrinkage occurred after 6 to 15 seconds of activation, and the RLN touched the Harmonic ACE. At a 1-mm distance, there were 2 adverse EMG events found after 25 seconds of activation. For Harmonic ACE+, there was no adverse EMG event observed when activated at 1- and 3-mm distances from the RLN. At a 0-mm distance, 2 adverse EMG events occurred after 6 to 10 seconds of activation. CONCLUSION: The safe distance of Harmonic ACE and ACE+ was 4 and 1 mm, respectively, in the swine models. Harmonic ACE+ is safer than Harmonic ACE because it did not cause any tissue shrinkage. Surgeons need to understand the characteristics of devices for safe operation.

Transoral Robotic Thyroidectomy

Transoral approach for thyroidectomy recently gains a lot of attention among the thyroid surgeons, with definite merits over previously developed remote-access approaches. The approach not only resulted in the ideal cosmetic outcome but less postoperative pain with smaller dissection plane in comparison with other approaches. We have successfully introduced the robotic surgical system and its related techniques to this transoral surgical approach for thyroidectomy, which enables the surgeon to have the three-dimentional operative vision and to use the articulating instruments to enhance th eoptimal surgical outcomes. Herein, our unique procedures of transoral robotic thyroidectomy (TORT) are described, and possible advantages and disadvantages of the operation are discussed.

Extent of central lymph node dissection for papillary thyroid carcinoma in the isthmus

PURPOSE: The incidence of papillary thyroid carcinoma (PTC) arising from the isthmus is low; however, these tumors have aggressive clinical and pathological features. Moreover, the existing guidelines regarding the extent of surgery for this type of tumor are unclear. METHODS: This study enrolled 282 patients who underwent total thyroidectomy with bilateral central lymph node dissection. The patients were divided into 2 groups based on the location of the median line of the PTC. Group I included patients in whom the median line was located between the lateral margins of the trachea; group II included all others. We compared the 2 groups and conducted a multivariate analysis to assess risk factors for contralateral node metastasis from a PTC arising from the isthmus. RESULTS: Patients in group I had significantly higher frequencies of extrathyroidal extension and central lymph node metastasis. Group I also had a higher frequency of contralateral node metastasis, and a tumor size >1.0 cm was identified as an independent risk factor for contralateral node metastasis among patients in this group. CONCLUSION: Bilateral central lymph node dissection could be considered for patients with isthmic PTCs >1.0 cm in size who have clinically suspicious node metastasis.

Significance of micrometastases in the calculation of the lymph node ratio for papillary thyroid cancer

PURPOSE: The lymph node ratio (LNR) is an important prognostic factor in papillary thyroid carcinoma (PTC), but micrometastases in cervical lymph nodes (LNs) are not of great clinical importance. In this study, we analyzed the accuracy of prediction of the prognosis depending on whether micrometastases were included in the number of metastatic LNs when calculating LNR. METHODS: The study included 353 PTC patients who underwent total thyroidectomy with neck LN dissection, and calculated LNR by 2 methods according to whether micrometastases were included in the number of metastatic LNs: Method 1 did not and method 2 did include. To compare the predictive values of LNR by the 2 methods, correlation coefficients and receiver operating characteristic (ROC) curves were analyzed. RESULTS: Positive correlations were found between LNR and preablation stimulated thyroglobulin (sTg) levels in both methods, but the correlation between method 1 LNR and preablation sTg level was significantly stronger than that for method 2 (Fisher z = 1.7, P = 0.045). The areas under these 2 independent ROC curves were analyzed; the prognostic efficacy of method 1 LNR was more accurate than that of method 2 LNR, and the difference was statistically significant (P = 0.0001). CONCLUSION: Regional recurrence of PTC can be predicted more accurately by not including micrometastases in the number of metastatic LNs when calculating LNR.

Surgical Treatment Guidelines for Patients with Differentiated Thyroid Cancer: The Korean Association of Thyroid and Endocrine Surgeons (KATES) Guidelines Taskforce / 대한내분비외과학회지

No abstract available.

Total Thyroidectomy with Central Neck Dissection Using Harmonic Focus: A Randomized Clinical Trial / 대한내분비외과학회지

PURPOSE: The use of sealing devices such as Harmonic scalpel and Ligasure is increasing steadily in thyroid surgery. The Harmonic Focus (HF) is an ultrasonic device that enables simultaneous vessel sealing and tissue coagulation, designed for open surgery such as thyroidectomy. The aim of this study is to assess the efficiency and safety of HF use in thyroid surgery compared to Conventional Tying (CT). METHODS: A prospective study was conducted to compare the efficacy of HF versus CT. We evaluated 50 patients who underwent surgery for thyroid tumor at Korea University Anam Hospital. All patients underwent total thyroidectomy with central neck dissection after being randomly allocated into two groups: HF group and CT group. The differences in surgical outcomes and postoperative complications by device use, i.e. group assignment, were statistically analyzed. RESULTS: There were no differences in number of retrieved lymph nodes (P=0.595), number of resected parathyroid glands (P=0.330), immediate postoperative iPTH (P=0.252), length of hospitalization (P=0.375) between HF group and CT group. However, operative time was shorter in HF group than CT group (106.07±20.92 min vs. 136.54±38.24 min, P=0.046). Postoperative complications of wound infection, seroma, hematoma, chyle leakage, vocal cord palsy, and hypoparathyroidism did not differ between groups. CONCLUSION: HF is a safe, effective, and time-saving technique; outcomes are comparable with CT. Both intraoperative and postoperative variables were similar between groups. Future larger studies are warranted to further investigate the effect on postoperative complications.

Transoral endoscopic thyroidectomy for papillary thyroid microcarcinoma: initial experience of a single surgeon

PURPOSE: Recently, transoral endoscopic thyroidectomy (TOET) is receiving attention because it is regarded as a true minimally invasive surgery in that it does not leave scars on any part of the body and the area of flap dissection is similar to that of open surgery. In this study, we present the surgical procedures and initial outcomes of TOET in the treatment of papillary thyroid microcarcinoma (PTMC) patients. METHODS: The medical records of patients who underwent TOET for PTMC between July 2016 and February 2017 were retrospectively reviewed. Indication of TOET was PTMC without capsular invasion or lymph node metastasis on preoperative imaging studies. RESULTS: Ten female patients were enrolled. Seven patients underwent thyroid lobectomy and three patients underwent isthmusectomy. The mean age and tumor size was 43.3 ± 11.5 years and 0.6 ± 0.2 cm, respectively. Operation time for lobectomy and isthmusectomy was 121.1 ± 30.7 (range, 65–148) and 90.0 ± 9.2 minutes (range, 82–100 minutes), respectively. The mean number of retrieved lymph nodes was 2.7 ± 1.7. Two patients had transient vocal cord palsy, which recovered in three months. There was no case with subcutaneous emphysema, surgical site infection, postoperative bleeding, or mental nerve injury. CONCLUSION: TOET was feasible and could be performed safely for PTMC. TOET might become a new treatment option for the patients who do not want to leave visible scars on the body.

The Present and Future of Intraoperative Neuromonitoring in Thyroid Surgery / 대한내분비외과학회지

Injury to the recurrent laryngeal nerve is the most common and serious complication after thyroid surgery. Many different techniques have been described in the literature and interest in intraoperative neuromonitoring (IONM) has increased in an effort to prevent adverse events. IONM implicated for identification of the nerve and evaluation of its function during the operation. Continuous IONM was recently introduced and looks promising for early recognition and safe operation in the end. This paper describes the role of IONM, and its current and future issues.

Achievement of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative: recommended serum calcium, phosphate and parathyroid hormone values with parathyroidectomy in patients with secondary hyperparathyroidism / 대한외과학회지

PURPOSE: The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) 2003 has established guidelines for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease - minerals and bone disorder (CKD-MBD). This study evaluated parathyroidectomy in SHPT patients for the achievement of the NKF-K/DOQI-recommended values of serum calcium, phosphate, and parathyroid hormone (PTH). METHODS: Between January 2005 and December 2010, parathyroidectomy was performed as recommended by the NKF-K/DOQI guidelines in 81 patients with SHPT and CKD-MBD. Serum PTH, calcium, and phosphate levels were measured prior to and 6, 12, 36, and 60 months after parathyroidectomy. RESULTS: Calcium, phosphate, and PTH levels dropped shortly after parathyroidectomy; however, a slight increase showed in the long term. Calcium levels increased for up to 60 months. Phosphate and PTH levels increased for up to 36 months but tended to decrease slightly at 60 months. The mean values were within the target ranges, except for PTH at 36 months. The target parameters of serum phosphate (42.9-61.1% of patients) and serum calcium (a peak of 61.1% of patients at 36 months, but only 28.6% at 60 months) were achieved the most. Less than 34% of patients achieved the recommended range for PTH. CONCLUSION: Parathyroidectomy was not an optimal procedure for achieving all the biochemical parameters recommended by the NKF-K/DOQI. Although it was helpful in attaining the recommended values for serum calcium and phosphate in SHPT patients resistant to medical therapy, the PTH levels did not fall within the recommended range.

Antiadhesive effect and safety of oxidized regenerated cellulose after thyroidectomy: a prospective, randomized controlled study / 대한외과학회지

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

Robotic Adrenalectomy Using a Lateral Transperitoneal Approach: Initial Experience of Fifteen Consecutive Cases / 대한내분비외과학회지

PURPOSE: In this study, we report on our initial experience using the da Vinci-S® robotic surgical system in performance of laparoscopic adrenalectomy. METHODS: Fifteen patients, 11 with left adrenal tumors and four with right adrenal tumors, underwent robotic adrenalectomies using the lateral transperitoneal approach with the da Vinci-S® surgical system at the Korea University Anam Hospital, Seoul, Korea, between October 2009 and May 2012. RESULTS: The mean age of the patients was 45.5 (22~61) years, and the mean body mass index was 23.81 (18.0~28.57) kg/m². Eleven left adrenalectomies, four for primary aldosteronisms, four for pheochromocytomas, two for primary adrenal Cushing's adenoma, and one for myelolipoma, and four right adrenalectomies, two for the primary adrenal Cushing's adenomas, one for pheochromocytoma, and one for primary aldosteronism, were performed robotically. There was no conversion to traditional laparoscopic or open surgery. The mean size of the tumor was 2.54 (1.0~5.5) cm. The mean operative time was 208.2 (120~320) minutes, and the mean console time was 127.6 (75~212) minutes. No major postoperative morbidity was observed, and the mean length of hospital stay was 5.86 days. CONCLUSION: We found that the robotic systems, with magnified stereoscopic three-dimensional vision, elimination of tremor, and the ability to articulate and rotate the instruments, were ideal surgical tools for operation of adrenal lesion. Robotic adrenalectomy may be a safe and effective alternative to traditional laparoscopic adrenalectomy.

Efficacy of intraoperative parathyroid hormone monitoring to predict success of parathyroidectomy for secondary hyperparathyroidism / 대한외과학회지

PURPOSE: In secondary hyperparathyroidism (sHPT), it is unclear which criterion for intraoperative parathyroid hormone (ioPTH) decline performs best and whether ioPTH monitoring is sufficiently efficacious in predicting postoperative surgical cure by retrospective review. METHODS: In 80 parathyroidectomies for sHPT, patients with ioPTH monitoring and follow-up PTH assay were categorized into physiologically accepted and failed groups. Receiver operating characteristic (ROC) curves were used to identify the criterion with the best performance and to determine the regression equation for prediction of surgical success. RESULTS: There was a statistically significant difference in the percentage reduction of ioPTHs between the two groups (P < 0.05). With our criterion, cure was predicted with a sensitivity of 86% and specificity that could be improved to 60% using an 85% ioPTH decrease as cut-off level when this value was compared to the Miami Criterion. There was a slightly negative correlation between the natural logarithm of percentage reduction of ioPTH and percentage reduction of PTH at follow-up (R2 = 0.109, P = 0.003). CONCLUSION: ioPTH measurements are a useful tool for improvement of the cure rate of operations for sHPT. Because this study aimed at 40 minutes (ioPTH3) as an optimal process in the operation, we recommend using a criterion of more than 85% ioPTH decline at 40 minutes by use of the ROC curve, and the use of the presently calculated regression equation may enable prediction of success.

Circulating Tumor Cells Detected by RT-PCR for CK-20 before Surgery Indicate Worse Prognostic Impact in Triple-Negative and HER2 Subtype Breast Cancer / 한국유방암학회지

PURPOSE: Circulating tumor cells (CTC) clearly correlate with unfavorable outcomes for patients with metastatic breast cancer, but the long-term prognostic implications of CTC for molecular subtypes of operable breast cancer are not yet known. We explored the relationships between previously established prognostic factors and CTC in operable breast cancer, and the significance of CTC by breast cancer molecular subtype. METHODS: We retrospectively evaluated 166 patients with operable breast cancer (stage I-IIIA) diagnosed from April 1997 to May 2003. CTC were detected using cytokeratin-20 (CK-20) mRNA expression in peripheral blood samples that were collected just prior to surgery under general anesthesia. Clinicopathological characteristics of the cancer were analyzed according to CTC status. Metastasis-free survival (MFS) and overall survival (OS) were analyzed according to CTC status and breast cancer molecular subtype. RESULTS: CK-20 mRNA-positive CTC was detected in 37 of 166 patients (22.3%) and was not correlated with any previous clinical factors in univariate analysis (p>0.05). After a median follow-up of 100 months, the patients with CK-20 mRNA-positive CTC had less favorable outcomes in terms of MFS and OS than those without detectable CTC (log-rank p<0.05). Among molecular subtypes of operable breast cancer, the patients with CK-20 mRNA-positive CTC had shorter MFS and OS in triple negative and human epidermal growth factor 2 (HER2) breast cancer subtype (log-rank, p<0.05). CONCLUSION: CK-20 mRNA-positive CTC may lend insight into tumor progression as a prognostic indicator especially in the triple negative and HER2 subtypes of operable breast cancer.

Circulating Tumor Cells Detected by RT-PCR for CK-20 before Surgery Indicate Worse Prognostic Impact in Triple-Negative and HER2 Subtype Breast Cancer / 한국유방암학회지

PURPOSE: Circulating tumor cells (CTC) clearly correlate with unfavorable outcomes for patients with metastatic breast cancer, but the long-term prognostic implications of CTC for molecular subtypes of operable breast cancer are not yet known. We explored the relationships between previously established prognostic factors and CTC in operable breast cancer, and the significance of CTC by breast cancer molecular subtype. METHODS: We retrospectively evaluated 166 patients with operable breast cancer (stage I-IIIA) diagnosed from April 1997 to May 2003. CTC were detected using cytokeratin-20 (CK-20) mRNA expression in peripheral blood samples that were collected just prior to surgery under general anesthesia. Clinicopathological characteristics of the cancer were analyzed according to CTC status. Metastasis-free survival (MFS) and overall survival (OS) were analyzed according to CTC status and breast cancer molecular subtype. RESULTS: CK-20 mRNA-positive CTC was detected in 37 of 166 patients (22.3%) and was not correlated with any previous clinical factors in univariate analysis (p>0.05). After a median follow-up of 100 months, the patients with CK-20 mRNA-positive CTC had less favorable outcomes in terms of MFS and OS than those without detectable CTC (log-rank p<0.05). Among molecular subtypes of operable breast cancer, the patients with CK-20 mRNA-positive CTC had shorter MFS and OS in triple negative and human epidermal growth factor 2 (HER2) breast cancer subtype (log-rank, p<0.05). CONCLUSION: CK-20 mRNA-positive CTC may lend insight into tumor progression as a prognostic indicator especially in the triple negative and HER2 subtypes of operable breast cancer.