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Objective: This study aimed to develop and apply a prediction model to estimate the probability of lateral lymph node metastasis (LLNM) in patients with cN0 unilateral papillary thyroid carcinoma (PTC) with central lymph node metastasis (CLNM)., Setting: All study data were collected from a single tertiary hospital., Methods: Univariable and multivariable logistic regression analyses were used to explore independent predictors of LLNM in the derivation and internal validation cohorts, which were used to construct and validate a nomogram. Another 96 patients were included prospectively to evaluate the efficacy of this nomogram., Results: Maximum tumor diameter greater than 1.0 cm (OR, 2.712; 95% CI, 1.412-5.210), multifocality (OR, 2.758; 95% CI, 1.120-6.789), the number of CLNM ≥3 (OR, 2.579; 95% CI, 1.315-5.789), CLNM ratio ≥0.297 (OR, 2.905; 95% CI, 1.396-6.043), and tumors located in the upper portion (OR 2.846, 95% CI 1.151-7.039) were independent predictors associated with LLNM. The prediction model showed excellent discrimination with an AUC of 0.731 (95% CI, 0.635-0.827). Novel risk stratification for LLNM was constructed based on this nomogram. In the prospective cohort, we stratified these patients into three risk subgroups: low-, moderate-, and high-risk subgroups and we found that the probability of LLNM was positively correlated with the total points from the nomogram., Conclusion: This nomogram was applied in prospective clinical practice and distinguished PTC patients with a genuinely high risk of LLNM. Surgeons can use our nomogram to tailor the surgical plan and to credibly determine further postoperative therapy., 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 Ma, Li, Zheng and He.)

Robotic thyroidectomy is one of the most advanced surgical procedures used to manage benign and malignant thyroid nodules. However, complication risks such as tracheal injury still exists. Tracheal injury in robotic thyroidectomy is difficult to detect and is one of the life-threatening complications. This study reviews the current literature on the tracheal injury following robotic thyroidectomy and also discusses our findings on 2060 cases of robotic thyroidectomy via Da Vinci Surgical System performed in our department and finally presents 3 cases treated in our center. PubMed and Web of Science database were searched using Medical Subject Headings (Mesh) related to "tracheal injury" and "robotic thyroidectomy". The search was conducted without publication date limits. We reviewed the literature and summarized common causes, diagnosis and therapeutic options of tracheal injury in robotic thyroidectomy, which has been described in comparison studies or retrospective studies. Tracheal injury is often diagnosed when patients suffer from dyspnea and usually leads to severe postoperative consequences. Tracheal injury can be suspected in all patients having subcutaneous emphysema, pneumomediastinum, pneumothorax or dyspnea after robotic thyroidectomy. Tracheoscopy is necessary to determine the location and size of tracheal injury. In patients whose condition is stable and the injury is contained, conservative treatment is feasible. Certainly, primary closure or tracheotomy is necessary for patients with serious respiratory difficulty or pneumothorax., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Although the prognosis for papillary thyroid carcinoma (PTC) is generally good, a certain proportion of patients show recurrent or advanced disease, indicating the need for further development of targeted medications. The purpose of this study was to explore the interventional effects of colchicine on PTC and the potential mechanisms or targets. We obtained PTC-related targets from the database and colchicine targets by predicting them. We screened the common targets of colchicine and the PTC-related target histone deacetylase 1 (HDAC1) and verified through molecular docking that colchicine has a good affinity for HDAC1, i.e., colchicine may act on PTC by affecting HDAC1. We then used CCK-8, colony formation, mitochondrial membrane potential and apoptosis assays to confirm that colchicine could inhibit the proliferation and promote the apoptosis of PTC cells and verified by RT‒qPCR, Western blot, and cellular immunofluorescence assays that colchicine could inhibit the expression of HDAC1 in PTC cells. The cytotoxicity and inhibitory effect of colchicine on HDAC1 in PTC cells was stronger than that in normal thyroid cells. We then applied an HDAC1 inhibitor, pyroxamide, to verify that inhibition of HDAC1 inhibits proliferation and promotes apoptosis in PTC cells. Therefore, we conclude that colchicine can inhibit the proliferation and promote the apoptosis of PTC cells likely due to its inhibitory effect on HDAC1. This finding implies that colchicine may be helpful for therapeutic intervention in PTC and that HDAC1 may be a promising clinical therapeutic target., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To explore the safety and feasibility of bilateral axillo-breast approach （BABA） robot in the operation of thyroid cancer in obese women. Methods: The clinical data of 81 obese female patients who underwent da Vinci robotic thyroid cancer surgery（robotic group） at the Department of Thyroid and Breast Surgery, PLA 960 Hospital from May 2018 to December 2021 were retrospectively analyzed and compared with the clinical data of 106 obese female thyroid cancer patients who underwent open surgery（open group） during the same period. The age, body mass index（BMI）, mean time of surgery, mean postoperative drainage, tumor diameter, postoperative tumor stage, number of lymph node dissection in the central and lateral cervical regions, number of positive lymph nodes in the central and lateral cervical regions, postoperative cosmetic outcome satisfaction score, mean postoperative hospital stay and postoperative complications of all patients were counted. The results were analyzed using SPSS 26.0 statistical software, and the count data were compared using the χ ² test, and the measurement data were compared using the t test. Results: All patients completed the operation successfully, and there was no conversion in the robot group, postoperative pathological results were all composed of papillary thyroid carcinoma. The operation time in the robot group was（144.62±36.38） min, which was longer than that in the open group（117.06±18.72） min（ P <0.05）. The average age of the robot group was（40.25±9.27） years, which was lower than that of the open group（49.59±8.70） years（ P <0.05）. The satisfactory score of cosmetic effect in the robot group（9.44±0.65） was higher than that in the open group（5.23±1.07）（ P <0.05）. There was no significant difference in tumor diameter, BMI, average postoperative drainage, temporary hypoparathyroidism and recurrent laryngeal nerve injury, number of central and lateral cervical lymph node dissection, number of positive lymph nodes in the central and lateral cervical regions, and average postoperative hospital stay between the two groups. There was no permanent hypoparathyroidism and recurrent laryngeal nerve injury in both groups. Conclusion: The application of BABA pathway robot in thyroid cancer surgery in obese women is safe and feasible, and the cosmetic effect is better after operation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Operations for pediatric thyroid nodules are more complicated, and usually lead to longer scars, which may impair life quality in the long term. Bilateral axillo-breast approach robotic thyroidectomy (BABA RT) may provide a better alternative to conventional open thyroidectomy (COT) for pediatric thyroid nodules. Our study aimed at comparing the surgical and oncological outcomes of BABA RT and COT in pediatric patients. Methods: The data of 49 pediatric patients who consecutively underwent BABA RT or COT (20:29) between July 1998 and November 2021 in our center were retrospectively analyzed, including demographics, surgery extent, surgical outcomes, pathological characteristics, and oncological outcomes. Results: All BABA RT procedures were completed successfully without conversion to open operation. The BABA RT group consisted of 5 benign and 15 malignant cases, while the COT group consisted of 19 benign and 10 malignant cases. The operation time, drain removal time, and number of lymph nodes harvested by central lymph node dissection or lateral lymph node dissection were equivalent in the BABA RT and COT groups. Notably, the postoperative hospital stay of the BABA RT group was shorter than that of the COT group (8.5 [interquartile ranges (IQRs): 3] vs. 11 [IQR: 8] days, p  = 0.008). The aesthetic score of the BABA RT group was much higher than that of the COT group (9 [IQR: 1] vs. 6 [IQR: 1], p  < 0.001). There was no significant difference between the BABA RT and COT groups in hypoparathyroidism rate (transient, 5 vs. 4; permanent, 1 vs. 0). There was one case of chyle leakage in the COT group and no other complications in any group, such as recurrent laryngeal nerve injury. With a median follow-up of 101 (IQR: 189) months, one case of local relapse and one case of pulmonary metastasis in the COT group were documented. Conclusion: In the hands of experienced surgeons, robotic BABA thyroidectomy can be a safe and effective option for both benign and malignant thyroid nodules in children, including those with lymph node metastasis. Robotic BABA thyroidectomy can offer a better and faster postoperative course and a much better cosmetic result, which is crucial for pediatric thyroid patients.

Objective: To compare the surgical outcomes between the transoral-vestibular robotic thyroidectomy (TOVRT) and bilateral axillo-breast approach robotic thyroidectomy (BABART)., Methods: A total of 99 patients with papillary thyroid carcinoma but no distant metastasis were enrolled in this study from May 2020 to April 2021. Lobectomy or total thyroidectomy with central lymph node dissection were performed in all cases. All 99 patients were received an ultrasound guided fine needle aspiration biopsy prior to surgical intervention, out of which 49 patients underwent TOVRT, while rest 50 patients underwent BABART. During the procedure, intraoperative neuromonitoring system was used and all recurrent laryngeal nerves (RLNs) were preserved, additionally for TOVRT procedure, three intraoral ports or right axillary fold incision was used to allow for fine countertraction of tissue for radical oncological dissection. The clinical data including age, gender, height, weight, BMI, primary tumor size, number of central lymph node removed, central lymph node metastasis, operating time, total hospital stays, postoperative hospital stays, total postoperative drainage volume, postoperative pain score, cosmetic effect and complications were recorded and analyzed., Results: There were no significant differences in gender, height, weight, BMI and removed central lymph nodes between the two groups (P > 0.05). Patients accepted TOVRT were younger and had smaller primary tumor size than those who accepted BABART. The TOVRT group had a longer surgical time than the BABART group, but with smaller postoperative drainage volume and superior cosmetic effect (under visual analogue scale, VAS) (P < 0.05). There was no significant difference in lymph node metastasis, hospital stay and postoperative pain score (under numerical rating scale, NRS) between the two groups (P > 0.05). Last but not least, certain peculiar complications were observed in TOVRT group: paresthesia of the lower lip and the chin (one case), surgical site infection (one case) and skin burn (one case)., Conclusion: Transoral-vestibular robotic thyroidectomy is safe and feasible for certain patients, which could be considered an alternative approach for patients who require no scarring on their neck., (© 2022. The Author(s).)

The receptors of chemokines play a significance role in the aggressiveness of tumor. CXCR4/CXCR7 promote metastasis of papillary thyroid carcinoma (PTC). This study examined the expresssion of chemokine receptors CXCR4/CXCR7 in human tissue specimens of PTC and peritumoral nonmalignant tissues. The correlation between CXCR4/CXCR7 and the clinicopathological factors in PTC was also determined. CXCR4/CXCR7 were examined in 115 PTC tissues from 115 patients using immunohistochemistry. Staining intensity was compared with patients and tumor characteristics including gender, age, tumor size, capsule invasion, multifocality, lymph node metastasis, and nature of paracancerous tissue. [Statistics: rank sum test, Spearman rank order correlation test; p < 0.05]. Higher expression rates of CXCR4/CXCR7 exhibited in PTC compared with peritumoral nonmalignant tissues. The expression of them was correlated in cancer and paracancerous specimens. A trend toward higher CXCR4/CXCR7 expression was found among tumors showing positive lymph nodes and capsule invasion, while no association with sex, age, tumor size, and nature of paracancerous tissue. Number of lymph nodes was associated with higher intensity IHC staining for CXCR4/CXCR7. Intense staining for CXCR4 was also associated with multifocality. Expression of CXCR4/CXCR7 by PTCs was correlated with lymph node metastasis and capsule invasion. Although multiple bias, they were thought to play a significance role in the aggressiveness of PTC, which provides potential targets for therapeutic interventions.

As a pentacyclic triterpenoid compound, Ursolic acid (UA) broads range of biological effects. CXCL12 is a ligand for CXCR4 and CXCR7 proteins on thyroid cancer cells. Here we examined the effects of UA on the proliferation, migration and invasion of papillary thyroid carcinoma (PTCs) in a dose-manner. In addition, UA can reduce the expression levels of CXCR4 and CXCR7 in PTCs. In addition to this direct anticancer pathway, studies have shown that UA can play an anticancer role by affecting the secretion of CXCL12 in cancer-associated fibroblasts (CAFs). After treated with UA, normal fibroblasts and CAFs culture medium (CM) showed differential CXCL12 expression levels. We prepared fibroblast conditioned medium according to the intervention of UA, then cultured TPC-1 and B-CPAP cells with differential CM, and detected significant differences in the proliferation, migration and invasion of cancer cells. Our findings uncovered an indirect anticancer mechanism of UA. This cancer chemopreventive properties is expected to make UA a clinically useful chemopreventive agent.

Rationale: Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy that is almost always fatal and lacks effective systemic treatment options. Current treatments of ATC include surgery, radiation, and chemotherapy, used in combination when possible. In the aspect of immunotherapy, the biomarker of TMB-H and MSI-H may suggest that patients benefit from pembrolizumab. Programmed cell death-ligand 1 (PD-L1) is highly expressed in ATC but has not been written into the guidelines or approved by the FDA as a biomarker for thyroid cancer immunotherapy., Patient Concerns: A 55-year-old woman was admitted to our hospital because of a slight right-sided neck enlargement in November 2019., Diagnoses: The clinical diagnosis was ATC, pT3bN0M0, and stage IVB., Interventions: Oral administration of apatinib (250 mg 3 times daily) was initiated after surgery, but some unpleasant side effects emerged after 1 month of treatment. Next-generation sequencing revealed that the tumor harbored 2 mutations, HRAS p.Q61R and TP53 p.P278S, and PD-L1 staining was positive with a high expression. Thus, camrelizumab (programmed cell death protein 1 inhibitor) was combined with apatinib, and apatinib was changed to 250 mg once a day from March 2020., Outcomes: No adverse reactions were observed after the treatment immunotherapy combined with antiangiogenic drugs. Currently, the survival time of patients is more than 11 months, and the quality of life is not affected., Conclusion: This case suggests that immunotherapy in patients with ATC based upon PD-L1 evaluation provides a therapeutic option. Targeting programmed cell death protein 1/PD-L1 may provide a much-needed treatment option for patients with advanced ATC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

To evaluate the feasibility and safety of robotic lateral cervical lymph node dissection via BABA, 260 thyroid cancer patients with suspected level II, III, IV, and V b lymph node metastasis were selected. The lateral cervical compartment was exposed by splitting the sternocleidomastoid muscle longitudinally, and separating between the strap muscles and the anterior margin of the sternocleidomastoid muscle. The procedure was completed in 260 patients. Mean time for robotic lateral node dissection took 80 ± 21 min. The wound catheter was removed 6.3 days. Postoperative transient symptomatic hypocalcemia was observed in 51 patients, transient hoarseness in three, seroma in three, chyle leakage in two, and tracheal injury in one. 124 patients were confirmed to have lymph node metastasis on final pathological report. Average postoperative hospital stay was 6.5 days. Robotic lateral neck dissection by BABA is the acceptable operative alternative for thyroid cancer patients who wished to keep their surgical history private.

Objective: To evaluate surgical outcomes and the feasibility of robotic thyroidectomy and central neck dissection (CND)., Methods: The clinical data of 40 patients of papillary thyroid microcarcinoma underwent total thyroidectomy (or lobectomy and isthmusectomy) and CND using the Da Vinci system through axillo-bilateral-breast approach in Jinan Military General Hospital of People's Liberation Army from February to December 2014 were analyzed retrospectively (robotic group). Other forty patients of papillary thyroid microcarcinoma underwent total thyroidectomy (or lobectomy and isthmusectomy) and CND by open approach were selected as the control (open group). Cosmetic satisfaction was assessed after a month postoperation by the numerical score system. t-test and χ(2) test were used to compare the clinical characters, total operative time, intraoperative estimated blood loss, postoperative hospital stay, number of lymph nodes removed, visual analogue scale for pain, postoperative complications, and cosmetic effect between the 2 groups., Results: All 80 patients were diagnosed of papillary thyroid microcarcinoma. The total thyroidectomy (or lobectomy/isthmusectomy) with CND of 40 patients were successfully performed by da Vinci Si surgical system. The numbers of total thyroidectomy of robotic group and the open group were 36 and 37, respectively. The numbers of metastatic lymph nodes of robotic group and open group were 14 and 15, respectively. The operation time of the robotic group was (130±12) minutes, which was longer than that of open group (98±11) minutes (t=12.432, P<0.05). The study showed statistical significant difference between the two groups regarding the visual analog scale pain assessment (1.9±0.9 vs.3.9±1.1, t=8.900, P<0.05). There were no statistical significant difference of intraoperative estimated blood loss, postoperative hospital stay, number of lymph nodes removed, and the complication rate between the 2 groups.Postoperative cosmetic result was more satisfying on the robotic group (9.1±0.5) than open group (4.8±1.5) (t=17.200, P<0.05)., Conclusions: The robotic total thyroidectomy (or lobectomy and isthmusectomy) and CND has similar surgery safety and feasibility as open procedures. The robotic thyroidectomy is a good alternative surgical modality for patients with papillary thyroid microcarcinoma who wish to avoid neck scars.

The aim of this study was to evaluate outcomes for patients with papillary thyroid microcarcinoma (PTMC) treated at a single institution during a 162-month period and to determine which patients need aggressive treatment. Two hundred seventy-three patients with PTMC had subtotal or total thyroidectomy + prophylactic or therapeutic lymph node dissection. Clinical and histopathological characteristics of 273 patients were identified and statistically analyzed. The tumors were multifocal in 36.3 per cent of the patients with PTMCs. Fifty-six per cent had neck lymph node metastases at diagnosis. Large-sized tumor (over 5 mm), age older than 45 years, multifocality, bilaterality, and extrathyroidal extension were associated with subclinical central lymph node metastases. Ninety-six patients older than 45 years of age were upgraded from Stage I to III or IVA. Ten patients with lateral node recurrence or local recurrence in the residual thyroid had one or more risk factors. The high rates of multifocality and Level VI area subclinical lymph node metastasis were two important clinical and histopathological characteristics of PTMC. Patients who had one or more risk factors should receive more aggressive surgical management.

The aim of this study was to compare operating time, postoperative outcomes, and surgical complications of total thyroidectomy plus level III-IV and VI dissection between the no-tie technique using the Harmonic Focus and classic suture ligation for hemostasis. Fifty-four patients underwent total thyroidectomy plus level III-IV and VI dissection by classic suture ligation and 51 patients by the Harmonic Focus. There was obvious distinction as to the operating time between the Focus and classic group (102.8 and 150.1 minutes, respectively, P < 0.05). Drainage volume (202.7 ± 187.0 mL vs 299.7 ± 201.4 mL, P < 0.05) were significantly lower in the Focus group. Transient hypoparathyroidism had no statistically significant difference between the groups (17.6% vs 18.5%, P > 0 .05). No patient experienced nerve injury or permanent hypocalcemia. The use of Harmonic Focus for the control of thyroid vessels during thyroid surgery is reliable and safe. The device can offer extraordinary capabilities for delicate tissue grasping and dissection.