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Background: Multiple medications are more effective than single agents for postoperative pain management. We investigated the analgesic effects of an intravenous combination of acetaminophen and ibuprofen immediately after thyroidectomy. Methods: In this double‐blind clinical trial, 62 patients who underwent thyroidectomies were randomized to either the treatment (1000 mg acetaminophen, 300 mg ibuprofen) or control (1000 mg acetaminophen) group. Postoperative pain intensity was assessed using the visual analog scale (VAS) 0, 15, and 30 min after recovery room admission. Opioid rescue consumption was also recorded. Results: The VAS scores were significantly lower in the treatment than in the control group 15 [3 (2–4.3) vs. 5 (3–6); p = 0.015] and 30 [3 (2–4.3) vs. 4 (3–5); p = 0.018] min after recovery room admission, as were the opioid rescue dose requirements (p = 0.033). Conclusions: Combined intravenous acetaminophen and ibuprofen may be better than acetaminophen alone for immediately acute postoperative pain after thyroidectomy. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the impact of tumor size on T3b differentiated thyroid cancer prognosis. No significant difference was found in the prognosis of small T3b tumors compared to the T1 tumors. Disease-specific survival, disease-free survival, and overall survival were significantly lower only in large T3b tumors compared to T2 and T3a. If T3b tumors are 2 cm or smaller, downstaging may be considered. The modified T category, reclassifying T3b (≤2 cm) as T1, showed better staging performance than the existing category. Adopting this modified T category could improve the prognostic accuracy of the AJCC/TNM staging. The prognostic significance of tumor size in T3b differentiated thyroid cancer (DTC) remains debated and underexplored. This study aimed to examine the varying impact of T3b based on tumor size, analyzing disease-specific survival, disease-free survival, and overall survival. A retrospective review of 6282 DTC patients who underwent thyroid surgery at Seoul St. Mary's Hospital from September 2000 to December 2017 was conducted. T3b was classified into three subcategories, T3b-1 (≤2 cm), T3b-2 (2–4 cm), and T3b-3 (>4 cm), using the same size criteria for T1, T2, and T3a. T3b-1 showed no significant difference in disease specific survival compared to T1, and both disease-free and disease-specific survival curves were sequentially ranked as T1, T3b-1, T2, T3a, T3b-2, and T3b-3. The modified T category, reclassifying T3b-1 as T1, demonstrated superior staging performance compared to the classic T category (c-index: 0.8961 vs. 0.8959 and AUC: 0.8573 vs. 0.8518). Tumors measuring 2 cm or less within the T3b category may require downstaging, and a modified T category could improve the precision of prognostic staging compared to the current T category. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the impact of age and BRAFV600E mutation on papillary thyroid cancer (PTC) recurrence. Among patients with BRAFV600E-positive PTC, those under 35 years of age had a significantly higher risk of recurrence than those over 55 years. However, in BRAFV600E-negative patients, age had no impact on the risk of recurrence. These findings emphasize the importance of considering age and mutation status in tailoring PTC treatment and follow-up. BRAFV600E positivity is associated with increased aggressiveness of papillary thyroid cancer (PTC), and age is an important prognostic factor. However, the association between age and BRAFV600E positivity and the recurrence risk has not been investigated. This study aimed to investigate the impact of age on recurrence between patients with BRAFV600E-positive and -negative PTC. Patients with PTC who underwent initial thyroid surgery between January 2010 and December 2018 at Seoul St. Mary's Hospital (Seoul, Republic of Korea) were retrospectively reviewed. The BRAFV600E-positive (n = 1768) and BRAFV600E-negative groups (n = 428) were divided into two subgroups: younger (<35 years) and older groups (≥55 years). In the BRAFV600E-positive group, the younger group exhibited higher lymphatic and vascular invasion rates, more positive lymph nodes, higher lymph node ratios, and higher recurrence rates than the older group (5.9% vs. 2.1%). Multivariate analysis revealed that age, lymphatic invasion, and N category were significant risk factors in the BRAFV600E-positive group. In the BRAFV600E-positive group, the younger group had a higher recurrence risk than the older group (OR, 2.528; 95% confidence interval, 1.443–4.430; p = 0.001). In the BRAFV600E-negative group, age had no impact on recurrence risk. These results contribute to tailored treatment strategies and informed patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: Multifocality is often found in PTC. There are contradicting evidences regarding clinical implications of cancer laterality in multifocal PTC. The current study compared the clinicopathological characteristics and the long-term oncological outcomes of bilateral and unilateral multifocal PTC. Patients with bilateral PTC were more likely to present with aggressive features, including high tumor stage, cervical LN metastasis, gross ETE, and lymphatic and perineural invasion. On the multivariate analysis using Cox regression, gross ETE, perineural invasion, LN metastasis, N1b stage, and RAI therapy were significant risk factors of recurrence. However, bilaterality was not associated with an increased risk of recurrence. In order to reduce selection bias, a subgroup analysis of patients who underwent total thyroidectomy was conducted using propensity score matching. After matching, unilateral multifocality, vascular invasion, and RAI therapy were significant risk factors of recurrence. Patients with unilateral multifocal PTC showed significantly poorer DFS than those with bilateral PTC on the Kaplan-Meier analysis. Papillary thyroid cancer (PTC) is commonly characterized by multifocality, which is associated with aggressive features and a less favorable prognosis. The current study aimed to compare the clinicopathologic characteristics and long-term oncological outcomes of bilateral and unilateral multifocal PTC. The medical records of 1745 patients with multifocal PTC who underwent thyroid surgery at Seoul St. Mary's Hospital were retrospectively reviewed. The clinicopathological characteristics and recurrence rates were compared based on cancer laterality. Further, 357 patients who underwent total thyroidectomy were matched to investigate the recurrence risk and disease-free survival (DFS). Before propensity score matching (PSM), there was no significant difference in the recurrence rate between the bilateral and unilateral multifocal PTC groups. Cancer laterality was not a predictor of DFS based on the Cox regression analyses. However, after PSM, unilateral multifocality was associated with a significantly high risk of recurrence. Similarly, unilateral multifocality was associated with a significantly poor DFS based on the Kaplan–Meier analysis. Compared with bilateral PTC, unilateral multifocal PTC was associated with a poor DFS. A comprehensive preoperative examination should be performed to detect multifocality before the initial surgical intervention for optimal treatment. Postoperative short-term follow-up is recommended for unilateral multifocal PTC for recurrence surveillance. [ABSTRACT FROM AUTHOR]

Simple Summary: In a retrospective study, researchers analyzed data from 909 patients with papillary thyroid carcinoma (PTC) who underwent thyroidectomy and neck dissection. The aim was to validate the relationship between lymph node ratio (LNR) and recurrence in patients with fewer than six lymph nodes examined after surgery. Over an average follow-up of 127.24 ± 33.6 months, recurrences occurred in 5.1% of the patients. The analysis identified an LNR ≥ 0.29 as an independent prognostic factor for recurrence. This means that patients with an LNR equal to or higher than 0.29 had a higher likelihood of recurrence compared to those with a lower LNR. These findings highlight the importance of considering LNR as a valuable prognostic marker for PTC patients with limited lymph node examination. Incorporating LNR into risk assessment can improve recurrence prediction and help guide treatment strategies. However, further prospective studies are needed to validate these results and determine their clinical implications in managing PTC patients. The American Thyroid Association risk stratification system suggests that having >5 metastatic lymph nodes (LNs) increase the recurrence risk in patients with papillary thyroid carcinoma (PTC). However, little is known about PTC with <5 harvested LNs. This study aimed to stratify patients with low-LN-yield (low-LNY) PTC based on lymph node ratios (LNRs). From 2007 to 2017, 6317 patients who underwent thyroidectomies were diagnosed with PTC at Seoul St. Mary's Hospital, and 909 patients with low LNYs were included in the study. Tumor recurrence was compared based on LNR. The LNR cutoff was determined using a receiver operating characteristic curve. Forty-six patients (5.1%) experienced recurrences over a mean follow-up period of 127.24 ± 33.6 months (range, 5–190 months). The cutoff for the low-LNR (n = 675) and high-LNR (n = 234) groups was 0.29 (AUC = 0.676, 95% CI = 0.591–0.761, p < 0.001). The recurrence rate was significantly higher in the high-LNR group compared to the rate in the low-LNR group (12.4% vs. 2.5%, p < 0.001). Multivariate analysis using Cox regression revealed that tumor size and LNR ≥ 0.29 were independent prognostic factors for recurrence. Therefore, LNR can be utilized to stratify the risk of recurrence in patients with low-LNY PTC. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, selpercatinib, a highly selective inhibitor of RET receptor tyrosine kinase, has been used for RET-altered thyroid cancer. However, real-world data of its effectiveness and safety in various clinical situations are lacking. We present four cases of patients with advanced thyroid cancer who were treated with selpercatinib with variable clinical situations. Selpercatinib showed good efficacy in all four patients without significant side effects. Despite facing varying clinical obstacles of the real world, selpercatinib safely proved remarkable therapeutic efficacy, although drug safety and durability through long-term use should be further validated. Recently, selpercatinib, a highly selective inhibitor of RET receptor tyrosine kinase, has been used for RET-altered thyroid cancer. We present four cases of patients with advanced thyroid cancer who were treated with selpercatinib. The first patient was a 63-year-old male with advanced medullary thyroid cancer (MTC) treated with vandetanib. Six months ago, he had an intracranial hemorrhage and swallowing difficulty. He started selpercatinib with percutaneous endoscopic gastrostomy (PEG). For 11 months, a partial response (PR) was observed stably with PEG administration without any more cardiovascular events. The second patient was a 67-year-old female with advanced MTC treated with vandetatib. After selpercatinib treatment, a PR was observed for most metastatic sites, including choroidal metastasis. The third patient was a 32-year-old female with advanced papillary thyroid cancer (PTC) without history of systematic treatment. For six months, a PR was observed at her metastatic site with manageable adverse events. The last patient was a 59-year-old female with advanced PTC treated with lenvatinib. She suffered from a panic disorder and pleural pain due to metastasis during lenvatinib treatment. After selpercatinib treatment, her pain and panic symptoms were improved. Facing varying clinical obstacles of the real world, selpercatinib safely proved remarkable therapeutic efficacy regardless of previous treatment or metastatic site. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the prognosis for thyroid cancer is favorable with a low mortality rate, the recurrence rate is high and predictors of re-recurrence and disease-specific mortality have not been established. This study revealed that multiple recurrences of thyroid cancer are associated with a higher mortality rate than a single recurrence, and the optimal treatment for the first recurrence is surgery. The lymph node ratio is a more suitable prognostic predictor than the number of positive lymph nodes in patients who undergo re-operation for the first recurrence of thyroid cancer. The purpose of this study was to establish the risk factors for re-recurrences and disease-specific mortality (DSM) in recurrent thyroid cancer. Patients with recurrent thyroid cancer who underwent initial thyroid surgery from January 2000 to December 2019 at Seoul St. Mary's Hospital (Seoul, Korea) were assessed. Clinicopathological characteristics and long-term oncologic outcomes were compared between patients with one recurrence (n = 202) and patients with re-recurrences (n = 44). Logistic regression and cox-regression analyses were conducted to determine the risk factors for re-recurrences and DSM, respectively. Receiver-operating characteristic curve analysis was performed to determine the cutoff value for lymph node ratio (LNR) as a predictor of re-recurrences. DSM was significantly higher in the re-recurrence group compared with the single-recurrence group (6.8% vs. 0.5%, p = 0.019). Surgical treatment at the first recurrence significantly lowered the risk of re-recurrences. Age (≥55), male sex, and LNR (≥0.15) were independent significant risk factors for re-recurrences in patients who underwent surgery at the first recurrence. Surgical resection is the optimal treatment for initial thyroid cancer recurrence. LNR at re-operation is more effective in predicting re-recurrence than the absolute number of metastatic LNs. [ABSTRACT FROM AUTHOR]

Objectives: Voice change after uncomplicated thyroidectomy has been an important issue in the field of thyroid surgery. The aim of this study was to promote understanding of voice change after uncomplicated thyroidectomy by analysing the results for a large number of patients from a single institute. Design: We retrospectively reviewed the medical records of 2879 consecutive patients who underwent thyroidectomy and voice evaluation between January 2014 and December 2019 in a single institute. All the patients had their vocal status assessed using videostroboscopy, acoustic voice analyses, aerodynamic study, and Thyroidectomy‐related Voice and Symptom Questionnaire (TVSQ) scores preoperatively and at 1, 3, and 6 months postoperatively. We analysed the pattern of voice changes over time and differences in voice parameters based on clinical factors. To confirm the usefulness of the TVSQ, the correlation between TVSQ scores and objective parameters was analysed. Lastly, predictive factors for persistent voice symptoms were analysed. Setting: Tertiary referral hospital. Results: The frequency ranges and TVSQ scores exhibited significant deterioration until 6 months following surgery. Among clinical factors, the extents of thyroidectomy and neck dissection were associated with worse voice parameters. The TVSQ score was significantly correlated with objective voice parameters. The extents of thyroidectomy and neck dissection were predictive of persistent voice symptoms at 6 months after thyroidectomy. Conclusion: After uncomplicated thyroidectomy, most voice parameters tended to recover, but some parameters remained aggravated even at 6 months after surgery. With more extensive surgery, worse voice quality and the higher risk of persistent voice symptoms may be anticipated. [ABSTRACT FROM AUTHOR]

Simple Summary: In the 8th edition of the AJCC/UICC TNM staging system, T3b is defined as gross extrathyroidal extension (gETE) invading only the strap muscles from a tumor of any size. However, defining T3b according to tumor size remains controversial. We created new T3b categories according to tumor size (T3b-1, tumor ≤ 2 cm in T3b; T3b-2, 2 cm < tumor ≤ 4 cm in T3b). There was a significant difference only in T3b-2 compared to T2. Novel methods of evaluating the effect of gETE according to tumor size should be considered in further revisions of the AJCC/UICC TNM staging system. The purpose of the present study was to compare the risk of recurrence between T2 and T3b papillary thyroid carcinoma (PTC) and the effect of tumor size on survival in T3b disease. A total of 634 patients with PTC who underwent thyroid surgery at a single center were retrospectively analyzed. Clinicopathological characteristics were compared according to the T category in the TNM staging system, with T3b divided into T3b-1 (tumor size, ≤2 cm) and T3b-2 (tumor size, 2–4 cm). Disease-free survival (DFS) and recurrence risk were compared between T2, T3b, T3b-1, and T3b-2. Tumor size was significantly larger in T2 than in T3b. A significant difference in recurrence was observed between T2 and T3b-2 but not between T2 and T3b-1. T3b-2 was identified as a significant risk factor for PTC recurrence. A significant difference in the DFS curve was observed between T2 and T3b-2. However, no significant differences in survival were observed between T2 and T3b or T3b-1. These results indicate that the prognostic impact of T3b may vary depending on tumor size. Further studies are required to determine the need for T classifications that account for tumor size and gETE invasion of the strap muscles. [ABSTRACT FROM AUTHOR]

Background and Objectives: Recently, the single-port (SP) robotic system was introduced for minimally invasive operative techniques. Thus, this study aimed to validate the safety and feasibility of SP trans-axillary robotic thyroidectomy (SP-TART) through experiences in a single tertiary institution. Materials and Methods: This study retrospectively analyzed 100 consecutive patients who underwent SP-TART from October 2021 to June 2022 in Seoul St. Mary's Hospital in Seoul, Korea. We analyzed the clinicopathological characteristics and perioperative outcomes, including complications. Results: Less than total thyroidectomy (LTT) was performed in 81, total thyroidectomy (TT) in 16, and TT with modified radical neck dissection (mRND) in 3 patients. The mean operation time (min) was 53.3 ± 13.7, 86.3 ± 15.1, and 245.7 ± 36.7 in LTT, TT, and TT with mRND, respectively. The mean postoperative hospital stay was 2.0 ± 0.2, 2.1 ± 0.3, and 3.7 ± 1.5 days, respectively. A total of 84 cases of thyroid cancer were included, and 97.6% of them (82 cases) were papillary carcinoma and the rest were follicular and poorly differentiated carcinomas. Regarding complications, five cases had major complications, including three cases of vocal cord palsy and two cases of transient hypoparathyroidism. Conclusions: SP-TART is safe and feasible with a short operation time and a short length of hospital stay. [ABSTRACT FROM AUTHOR]

Introduction: MegaShield® is a newly developed temperature-sensitive anti-adhesive containing micronized acellular dermal matrix. The aim of this study was to investigate the efficacy and safety of MegaShield® compared with Guardix-SG® in the prevention of adhesions in patients undergoing bilateral total thyroidectomy. Method: We conducted a multicenter trial between October 2018 and March 2020 in patients undergoing total thyroidectomy. The patients were randomly assigned to either the MegaShield® group or the Guardix-SG® group. The primary outcome was the esophageal movement using marshmallow six weeks after the surgery and the secondary outcome was the assessed adhesion score. The safety assessment was also evaluated. Results: The study included 70 patients each in the MegaShield® and control (Guardix-SG®) groups. Baseline clinical characteristics, the mean score of marshmallow esophagography, and the sum of adhesion scores were not statistically different between the two groups. Inferiority test demonstrated that the efficacy of MegaShield® is not inferior to that of Guardix-SG®. There were no device-related complications in both groups. Conclusion: The efficacy and safety of MegaShield® were not inferior than those of Guardix-SG®. MegaShield® demonstrated the potential of ADM as a potential future anti-adhesive agent. Trial registration: The name of trial registry CRIS (Clinical Research Information Service) https://cris.nih.go.kr/cris/index.jsp. (The full trial protocol can be accessed) Registration number: KCT0003204. [ABSTRACT FROM AUTHOR]

Simple Summary: The main findings of the study are that pectoralis nerve block II (PECS II) may be a valuable analgesic option that alleviates flap dissection pain and stress during a robot-assisted transaxillary thyroidectomy (RATT) and reduces opioid consumption in the early recovery phase. Patients who received PECS II experienced a more comfortable recovery and required fewer painkillers. PECS II may serve as a valuable new pain relief modality in addition to the multimodal analgesic strategy for patients undergoing RATT. Although we have yet to investigate the optimal block duration, regions of sensory loss, optimal technique, and possible complications, our preliminary study suggests that PECS II reduces flap dissection pain and thus promotes recovery. Appropriate analgesia during RATT remains challenging, but is a key issue for postoperative recovery. A further prospective investigation is required to validate our results and establish the optimal pain control regimen for patients undergoing RATT. Few studies have examined the clinical utility of ultrasonography-guided pectoralis nerve block II (PECS II) during wide flap dissection of a robot-assisted transaxillary thyroidectomy (RATT). We assessed the ability of PECS II to reduce postoperative pain. We retrospectively reviewed 62 patients who underwent elective RATT from December 2021 to April 2022 at Seoul St. Mary's Hospital (Seoul, Korea). The patients were divided into a block group (n = 28, 50.9%) and no-block group (n = 27, 49.1%). Pain was measured using a visual analog scale (VAS) at 4, 10, 20, 25, 35, and 45 h after surgery, and the requirements for rescue painkillers in the post-anesthesia care unit and ward were recorded. The VAS scores did not differ significantly between the two groups at 4 h postoperatively. The block group had significantly lower VAS scores at 10 and 25 h (p = 0.017 and p = 0.034, respectively). The block group required fewer painkillers in the post-anesthesia care unit than the no-block group, although the difference was not statistically significant in the ward. PECS II may serve as a new pain relief modality and valuable addition to the current multimodal analgesic strategy for patients undergoing RATT. [ABSTRACT FROM AUTHOR]

Simple Summary: The lymph node ratio (LNR) is an emerging predictive marker for recurrence in papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the association between LNR and disease-free survival (DFS) in patients with N1b PTC. Unlike that in the lateral or whole neck, LNR in the central compartment (CLNR) was found to have prognostic significance. The high-CLNR group (CLNR ≥ 0.7) had worse DFS and was 4.5 times more likely to experience recurrence in patients with N1b PTC. The lymph node ratio (LNR) indicates the number of metastatic lymph nodes (LNs) to the total number of LNs. The prognostic value of LNR in papillary thyroid carcinoma (PTC) and other solid tumors is known. This study aimed to investigate the relationship between LNR and disease-free survival (DFS) in patients with PTC with lateral LN metastases (N1b PTC). A total of 307 patients with N1b PTC who underwent total thyroidectomy and therapeutic central and lateral LN dissection were retrospectively analyzed. The DFS and recurrence risk in the patients with LNR, central-compartment LNR (CLNR), and lateral-compartment LNR (LLNR) were compared. The mean follow-up duration was 93.6 ± 19.9 months. Eleven (3.6%) patients experienced recurrence. Neither LNR nor LLNR affected the recurrence rate in our analysis (p = 0.058, p = 0.106, respectively). However, there was a significant difference in the recurrence rates between the patients with low and high CLNR (2.1% vs. 8.8%, p = 0.017). In the multivariate analysis, CLNR ≥ 0.7 and perineural invasion were independent predictors of tumor recurrence. High CLNR was associated with an increased risk of recurrence, and was shown to be a significant predictor of prognosis in patients with N1b PTC. [ABSTRACT FROM AUTHOR]

Simple Summary: In papillary thyroid carcinoma (PTC), staging classification of gross and minimal extrathyroidal extension (ETE) has been recently modified in the eighth edition of the American Joint Commission on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system. In this study, we compared the clinicopathological characteristics and recurrence rates between minimal and gross ETE. No significant differences in the recurrence and disease-free survival rates were found between the two groups. Whether gross ETE invading strap muscles (T3b) only could be a risk factor for recurrence in PTC remains questionable. The presence of extrathyroidal extension (ETE) is associated with locoregional recurrence and distant metastases in papillary thyroid carcinoma (PTC). This study was designed to compare the recurrence risk between minimal ETE (mETE) and gross ETE (gETE) in patients with PTC using propensity score matching. In this study, 4452 patients with PTC who underwent thyroid surgery in a single center were retrospectively analyzed, and clinicopathological characteristics were compared according to the ETE status. Disease-free survival (DFS) and recurrence risk were compared between mETE and gETE after propensity score matching. The mean follow-up duration was 122.7 ± 22.5 months. In multivariate analysis, both mETE and gETE were not associated with recurrence risk before propensity score matching (p = 0.154 and p = 0.072, respectively). After propensity score matching, no significant difference in recurrence rates was observed between the two groups (p = 0.668). DFS of the gETE group did not significantly differ from that of the mETE group (log-rank p = 0.531). This study revealed that both mETE and gETE are not independent risk factors for the risk of recurrence in PTC. Our findings suggest that gETE invading strap muscles only might not be associated with worse oncological outcomes in PTC. [ABSTRACT FROM AUTHOR]