A modified, single-incision, gasless, endoscopic thyroidectomy and bilateral central neck dissection via axillary approach technique for bilateral papillary thyroid microcarcinoma: A preliminary report.

Background: Our objective was to assess the viability and oncological security of a gasless, transaxillary single-incision endoscopic procedure for performing total thyroidectomy and bilateral central neck dissection (TT + BCND). This study focused on patients diagnosed with bilateral papillary thyroid microcarcinoma (PTMC). Method: Between April 2020 and November 2021, 22 patients with bilateral PTMC underwent single-incision, gasless, transaxillary endoscopic TT + BCND. The patients' clinicopathologic characteristics, surgical completeness and complications were analyzed. Result: Single-incision, gasless, transaxillary endoscopic TT + BCND was successful performed in all patients. The median (IQR) total surgical time was 143 (85-160) min. Only two patients experienced transient unilateral RLN palsy or transient hypocalcemia. All these complications resolved within 1 month after surgery. The median duration of hospital stay after surgery was 4 (3-4.5) days. The median hospitalization expense for these patients was 3848 (3781-4145) USD. The median number of lymph node yielded was 10.5 (8-15). The cosmetic outcomes were well-received by all individuals. Conclusion: In certain cases, gasless, transaxillary endoscopic TT + BCND procedure performed through a single incision proved to be a secure alternative for managing bilateral PTMC.

An integrated model incorporating deep learning, hand-crafted radiomics and clinical and US features to diagnose central lymph node metastasis in patients with papillary thyroid cancer.

OBJECTIVE: To evaluate the value of an integrated model incorporating deep learning (DL), hand-crafted radiomics and clinical and US imaging features for diagnosing central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC). METHODS: This retrospective study reviewed 613 patients with clinicopathologically confirmed PTC from two institutions. The DL model and hand-crafted radiomics model were developed using primary lesion images and then integrated with clinical and US features selected by multivariate analysis to generate an integrated model. The performance was compared with junior and senior radiologists on the independent test set. SHapley Additive exPlanations (SHAP) plot and Gradient-weighted Class Activation Mapping (Grad-CAM) were used for the visualized explanation of the model. RESULTS: The integrated model yielded the best performance with an AUC of 0.841. surpassing that of the hand-crafted radiomics model (0.706, p < 0.001) and the DL model (0.819, p = 0.26). Compared to junior and senior radiologists, the integrated model reduced the missed CLNM rate from 57.89% and 44.74-27.63%, and decreased the rate of unnecessary central lymph node dissection (CLND) from 29.87% and 27.27-18.18%, respectively. SHAP analysis revealed that the DL features played a primary role in the diagnosis of CLNM, while clinical and US features (such as extrathyroidal extension, tumour size, age, gender, and multifocality) provided additional support. Grad-CAM indicated that the model exhibited a stronger focus on thyroid capsule in patients with CLNM. CONCLUSION: Integrated model can effectively decrease the incidence of missed CLNM and unnecessary CLND. The application of the integrated model can help improve the acceptance of AI-assisted US diagnosis among radiologists.

Right gasless transaxillary endoscopic total thyroidectomy (RGTETT) with video: our experience with the posterior approach: Lei's seven-sinking method.

Our video demonstrates a modified gasless transaxillary endoscopic thyroid surgery with the posterior approach for bilateral low-risk thyroid cancer. In this paper, we provided a detailed introduction to the right gasless transaxillary endoscopic total thyroidectomy surgical procedure for bilateral low-risk thyroid cancer, and briefly summarized the Lei's seven-sinking method: sinking the clavicular head of the sternocleidomastoid muscle (CHSCM); sinking the cervical vascular sheath; sinking the right wall of the esophagus; sinking the right recurrent laryngeal nerve (RLN); sinking the trachea; sinking the left RLN and sinking the thyroid. A 5-cm incision was made starting from the anterior axillary line along the natural fold at the axilla. A trocar was placed in the axillary incision approximately 3-5 cm away from the side of the breast and slightly below the anterior axillary line. Using blunt dissection and electrocautery, a working space was created by elevating a subcutaneous flap above the pectoralis major muscle. The thyroid bed was accessed through the two heads of the SCM, and then the thyroid was separated from the strap muscles. Thyroidectomy and central lymph node dissection were fully endoscopically performed with the posterior approach using conventional endoscopic instruments. Through the posterior approach and the operation steps of the seven-sinking method, total thyroidectomy and bilateral central lymph node dissection can be achieved relatively easily.

A propensity score matching analysis of gasless endoscopic transaxillary thyroidectomy with five-settlement technique versus conventional open thyroidectomy in patients with papillary thyroid microcarcinoma.

BACKGROUND: In a previous study, we proposed a novel anatomy-based five-settlement method for transaxillary endoscopic thyroidectomy (fs-TAT) for patients with papillary thyroid carcinoma. The safety of this new method has been reported in a retrospective study of a single cohort. The safety and short-term oncological outcome of this method was confirmed by comparing it with conventional open surgery (COT) in patients with papillary thyroid microcarcinoma. METHODS: The medical records of patients who underwent fs-TAT or COT by a single surgeon from February 2019 to December 2021 were reviewed retrospectively. All patients were diagnosed with papillary thyroid microcarcinoma and underwent lobectomy and ipsilateral central compartment neck dissection. Propensity score matching was used to compare the technical safety and short-term oncologic outcomes of fs-TAT and COT for the purpose of reducing potential selection bias. Reporting was consistent with the STROCSS 2021 guidelines. RESULT: After propensity score matching, 460 (fs-TAT: 230; COT: 230) patients remained in the study population. There were no significant differences in sex, age, tumor size, Hashimoto's thyroiditis, or tumor multifocality between the groups. The operative time was longer [104.5 (90.3, 120.0) vs. 62.0 (52.0, 76.0), P < 0.001] and the total postoperative drainage volume [135(90, 210) vs. 75 (55, 115), P < 0.001] was greater in the fs-TAT group than in the COT group. However, intraoperative bleeding [3.0 (2.0, 5.0) vs. 5.0 (5.0, 7.5), P < 0.001] was greater, and the median number of lymph nodes yielded [5.0 (2.3, 8.0) vs. 7.0 (5.0, 11.0), P < 0.001] was greater in the COT group than in the fs-TAT group. The groups exhibited no significant difference in the rate of complications (fs-TAT: 2.2% vs. COT: 2.6%, P = 0.856), rate of positive lymph nodes (fs-TAT: 32.2% vs. COT: 36.5%, P = 0.377), length of postoperative hospital stay (3 days vs. 3 days, P = 0.305) or total medical costs (26,936 vs. 26,549, P = 0.144). CONCLUSION: Compared to conventional open surgery, fs-TAT offered excellent safety and acceptable short-term oncological outcomes in a selected cohort of patients with papillary thyroid microcarcinoma.

Analysis of scene-guided camera assistance in transaxillary gasless endoscopic thyroidectomy: a minor improvement in operative technique.

Background: Transaxillary gasless endoscopic thyroidectomy (TGET) is a widely performed operation, but its side view angle and instrument interference have caused concerns for most surgical groups. The aim of this study was to introduce scene-guided camera assistance (SGA) and analyze its role in facilitating TGET. Methods: We put forward key points for camera holders, including one pivot, two positions, and three planes, and separated TGET operations into five parts. We also established the view angle for each part of the operation for the camera holder to follow. Then, we reviewed 416 patients who underwent TGET with or without SGA and analyzed their demographic characteristics, operative outcomes, pathologic outcomes, and early complications. Results: The TGET and TGET-SGA groups were similar in terms of age, sex ratio, height, weight, tumor size, Hashimoto's thyroiditis ratio, and cN1 ratio. The operation time and postoperative hospital stay were significantly longer in the TGET group than in the TGET-SGA group (114.43 ± 17.20 minutes vs. 101.82 ± 19.39 minutes and 3.16 ± 0.77 days vs. 2.16 ± 0.55 days, respectively, P < 0.001). The account of retrieved lymph nodes was less in the TGET group than in the TGET-SGA group (5.61 ± 4.27 vs. 6.57 ± 4.96, P = 0.038). Conclusion: SGA provided guidance for camera holders, and the data showed that it was an improvement for TGET operations.

Multicenter Randomized Double-Blind Phase III Trial of Donafenib in Progressive Radioactive Iodine-Refractory Differentiated Thyroid Cancer.

PURPOSE: The phase II/III study of donafenib was initiated when there was no available treatment indicated for Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Donafenib, an oral tyrosine kinase inhibitor (TKI), showed good efficacy and tolerability in the phase II study. We aimed to further evaluate the antitumor activity and safety of donafenib in Chinese patients with RAIR-DTC. PATIENTS AND METHODS: This multicenter, double-blind, placebo-controlled, phase III study enrolled 191 patients with progressive RAIR-DTC and randomized in a ratio of 2:1 to donafenib (300 mg twice daily, n = 128) or matched placebo (n = 63). An open-label donafenib treatment period was allowed upon disease progression. The primary endpoint was progression-free survival (PFS) assessed by the independent review committee. The second endpoints include objective response rate (ORR), disease control rate (DCR), safety, etc. RESULTS: Donafenib demonstrated prolonged median PFS over placebo [12.9 vs. 6.4 months; hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.25-0.61; P < 0.0001] in Chinese patients with RAIR-DTC. Improved ORR (23.3% vs. 1.7%; P = 0.0002) and DCR (93.3% vs. 79.3%; P = 0.0044) were observed in the donafenib group over placebo. For donafenib, the most common grade ≥ 3 treatment-related adverse events (AE) included hypertension (13.3%) and hand-foot syndrome (12.5%), 42.2% underwent dose reduction or interruption, and 6.3% experienced discontinuation. CONCLUSIONS: Donafenib was well-tolerated and demonstrated clinical benefit in terms of improved PFS, ORR, and DCR in patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for patients with RAIR-DTC.

A novel anatomy-based five-settlement method for endoscopic thyroid lobectomy and ipsilateral central compartment neck dissection via gasless unilateral axillary approach: a preliminary report.

Background: Endoscopic thyroidectomy (ET) via gasless unilateral axillary (GUA) approach has been widely implemented worldwide. Based on our concept of mesothyroid excision in open surgery, we proposed a novel anatomy-based five-settlement method in ET via the GUA approach. This preliminary report aimed to explore the efficacy and safety of this method in patients with papillary thyroid carcinoma (PTC). Methods: PTC patients who underwent endoscopic ET and unilateral central compartment neck dissection (CCND) via GUA approach with the five-settlement method at the Department of General Surgery, Nanfang Hospital, Southern Medical University from March 2020 to December 2021 were retrospectively collected. The data included general clinicopathological characteristics, surgical information (including duration, complication, and clinicopathological features), and hospital stay information, and other medical records were documented. Results: In total, 521 patients underwent lobectomy and CCND under the GUA approach with the five-settlement method. The mean number of lymph nodes yielded (LNY) and positive lymph nodes (PLN) was 5.7 ± 4.3 (range, 1-30) and 1.0 ± 1.8 (range, 0-12), respectively. The incidence of transient recurrent laryngeal nerve injury was 1.1%. Chyle leakage and Horner's syndrome respectively occurred in one patient (0.2%). Five (0.9%) patients developed a hematoma. No severe complications or conversion to open surgery have occurred. Conclusion: The five-settlement method could be implemented safely and efficiently in ET+CCND via the GUA approach in selected PTC patients.

The lymph node yield in the initial lateral neck dissection predicts recurrence in the lateral neck of papillary thyroid carcinoma: a revision surgery cohort study.

BACKGROUND: This study aimed to evaluate the relationship between lateral lymph node yield (LLNY) and the ratio of lateral positive lymph nodes to lymph node yield (LPLR) from initial lateral neck dissection (LND) in patients with papillary thyroid carcinoma (PTC), as well as the risk of recurrence in patients undergoing LND reoperations. METHODS: This retrospective cohort study enrolled patients with PTC who underwent revision LND between 1 January 2012, and 31 December 2021. The initial and revised clinical data were retrieved. Patient demographics, clinicopathological features, clinical records, and follow-up information were also reviewed. LLNY and LPLR were determined during the initial LND. RESULTS: In total, 156 patients with PTC were included in this study, with a median follow-up of 36.5 months; 107 had recurrent lateral neck disease. The optimal LLNY and LPLR cutoff values for recurrent/persistent disease were 24.5 and 32.74%, respectively. The high-risk group (LLNY<25) had the lowest recurrence-free survival rate compared with to moderate-risk group (LLNY≥25, LPLR≥32.74%) and low-risk group (LLNY≥25, LPLR<32.74%) ( P <0.001). The moderate-risk group had lower recurrence-free survival than the low-risk group. Multivariate analysis revealed that an LLNY less than 25 in the initial LND was an independent risk factor for recurrence/persistence of lateral neck ( P <0.001). CONCLUSIONS: This study identified that LLNY and LPLR were associated with recurrence/persistence in PTC patients at the time of revision surgery was performed.

The learning curve for gasless transaxillary posterior endoscopic thyroidectomy for thyroid cancer: a cumulative sum analysis.

Gasless transaxillary posterior endoscopic thyroidectomy (GTPET) is a new approach for thyroid cancer. It allows en bloc resection of the thyroid and central lymph nodes. Few studies have reported on the learning curve for GTPET.We examined the learning curve of GTPET for thyroid cancer by cumulative sum (CUSUM) analysis by retrospectively analyzing patients who underwent hemithyroidectomy with ipsilateral central neck dissection between December 2020 and September 2021 at a tertiary medical center, including the first patient. Moving average analysis and sequential time-block analysis were used for validation. Data on the clinical factors between the two periods were compared. In the overall cohort, the average time for GTPET for thyroid cancer was 113.25 min to harvest an average of 6.4 central lymph nodes. The CUSUM curve of the operative time indicated an inflection point after 38 patients. Moving average analysis and sequential time-block analysis validated the number of procedures needed for GTPET proficiency. (124.05 min vs. 107.63 min for the unproficient period vs. proficient period, respectively; P < 0.001) The number of retrieved lymph nodes was not associated with a certain level of proficiency per the learning curve. The main complication during the surgeon's unproficient period was transient hoarseness (3/38), which was similar to that in their proficient period (2/73, p = 0.336). Proficiency in GTPET is associated with performing more than 38 procedures. Standard course training and instruction on careful management are required prior to introducing the procedure.

Efficacy and safety of selpercatinib in Chinese patients with advanced RET-altered thyroid cancers: results from the phase II LIBRETTO-321 study.

Background: Selpercatinib, a highly selective and potent REarranged during Transfection (RET) kinase inhibitor, is effective in advanced RET-altered thyroid cancer (TC). However, the efficacy and safety in Chinese patients are unknown. Patients and methods: In the open-label, multi-center phase II LIBRETTO-321 (NCT04280081) study, Chinese patients with advanced solid tumors harboring RET alterations received selpercatinib 160 mg twice daily. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DoR) and safety. Efficacy was assessed in the primary analysis set [PAS; treated patients with RET fusion-positive TC or RET-mutant medullary TC (MTC) confirmed by central laboratory] and all enrolled patients with MTC. Results: Of 77 enrolled patients, 29 had RET-mutant MTC and one had RET fusion-positive TC. In the PAS (n = 26), the ORR by IRC was 57.7% [95% confidence interval (CI), 36.9-76.6]. Median DoR was not reached and 93.3% of responses were ongoing at a median follow-up of 8.7 months. In all enrolled MTC patients (n = 29), the ORR by IRC was 58.6% (95% CI, 38.9-76.5). One RET fusion-positive TC patient treated for 23.4 weeks achieved a partial response at week 8 that was ongoing at cutoff. In the safety population (n = 77), 59.7% experienced grade ⩾3 treatment-emergent adverse events (TEAEs). TEAEs led to dose reductions in 32.5% (n = 25) and discontinuations in 5.2% [n = 4; 3.9% (n = 3) considered treatment related] of patients. Conclusions: Selpercatinib showed robust antitumor activity and was well tolerated in Chinese patients with advanced RET-altered TC, consistent with global data from LIBRETTO-001 (NCT04280081). ClinicalTrialsgov Identifier: NCT04280081 (first posted Feb 21, 2020).

Comparison of quality of life and cosmetic result between open and transaxillary endoscopic thyroid lobectomy for papillary thyroid microcarcinoma survivors: A single-center prospective cohort study.

BACKGROUND: Transaxillary endoscopic thyroidectomy has been introduced to achieve better cosmetic outcomes. However, the benefits of this technology on the patients' health-related quality of life (HRQoL) remain unclear. We aimed to investigate whether transaxillary endoscopic lobectomy is comparable to conventional open lobectomy in terms of QOL and cosmetic results in order to provide more evidence for establishing appropriate clinical decisions. METHODS: Between August 2019 and May 2020, transaxillary endoscopic lobectomy and conventional open lobectomy were performed in 73 and 99 patients with papillary thyroid microcarcinoma, respectively. HRQoL was assessed at 1, 3, 6, and 12 months after surgery using the Thyroid Cancer-Specific Quality of Life Questionnaire. The cosmetic outcomes were assessed 12 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS). RESULTS: No significant difference was observed in the surgical results between the two groups. However, the data showed that the average operative time and postoperative hospital stay of the transaxillary group were longer than those of the open group (p < 0.001). Both groups showed similar changes in the QOL scores over time. However, the transaxillary group had fewer complaints of the throat or oral problems at 1 month postoperatively than the open group (p < 0.001). During the follow-up, the cosmetic results of scars in the transaxillary group were significantly better than those in the open group (p < 0.05). Patients who underwent transaxillary endoscopic lobectomy had higher overall satisfaction with their scar appearance, determined using POSAS, at 12 months postoperatively. CONCLUSIONS: The current findings suggest that transaxillary endoscopic lobectomy may offer better cosmetic and HRQoL outcomes.

Lymph node yield in the initial central neck dissection (CND) associated with the risk of recurrence in papillary thyroid cancer: A reoperative CND cohort study.

BACKGROUND: To evaluate the relationship between lymph node yield (LNY) from the initial central neck dissection (CND) and the risk of recurrence in patients undergoing reoperative CND for papillary thyroid cancer (PTC). METHOD: We reviewed clinical data from all patients with pathologically proven PTC who underwent central neck and/or lateral neck dissection reoperations at Nanfang Hospital between 2012 and 2020. Patient demographics, tumor characteristics, clinical data and follow-up information were obtained. In the initial CND, the total number of lymph nodes removed (LNY), total positive nodes removed, and the percentage of positive lymph nodes to the number of lymph nodes removed (PLN%) were determined. RESULTS: A total of 162 patients were included in the study, with a median follow-up of 44 months. 62 had central neck disease recurrence. The optimal LNY and PLN% cut-off values for recurrence were 11 and 65%, respectively. Group 2 (LNY ≥ 11, PLN% < 65%) showed a significantly higher RFS rate than group 1 (LNY < 11 and PLN% < 65%; P < 0.001), group 3 (LNY < 11, PLN% ≥ 65%; P < 0.001), and group 4 (LNY ≥ 11, PLN% ≥ 65%; P = 0.038). Furthermore, group 4 had a higher RFS rate than group 1 (P = 0.008) and group 3 (P = 0.001). Multivariate analysis revealed that LNY < 11 in the central neck was an independent risk factor for recurrence/persistence in the initial surgery (P < 0.001). CONCLUSION: Higher LNY in central and neck dissections is associated with lower papillary thyroid cancer recurrence rates, which was confirmed by a reoperative CND procedure. To minimize the risk of recurrence and the need for secondary therapy, surgeons should perform compartment-oriented CNDs when indicated.

Association of the Collagen Signature in the Tumor Microenvironment With Recurrence and Survival of Patients With T4N0M0 Colon Cancer.

BACKGROUND: The current clinicopathological risk factors do not accurately predict disease recurrence in patients with T4N0M0 colon cancer. We hypothesized that the collagen signature combined with clinicopathological risk factors (new model) had a better prognostic value than clinicopathological risk factors alone (clinicopathological model). OBJECTIVE: This study aimed to establish a collagen signature in the tumor microenvironment and to validate its role in predicting the recurrence of T4N0M0 colon cancer. DESIGN: This was a retrospective study. SETTINGS: This study took place at a tertiary medical center. PATIENTS: Patients with T4N0M0 colon cancer who underwent surgery at our center between 2009 and 2015 (n = 416) were included. INTERVENTION: A total of 142 collagen features were analyzed in the tumor microenvironment in specimens of colon cancer by using second-harmonic generation imaging. A collagen signature was constructed using a least-absolute shrinkage and selection operator Cox regression model. MAIN OUTCOME MEASURES: The primary outcomes measured were disease-free survival and overall survival. RESULTS: The training and testing cohorts consisted of 291 and 125 randomly assigned samples, with recurrence rates of 19.9% and 22.4%. A 3-feature-based collagen signature predicted the recurrence risk at 1, 3, and 5 years, with the area under the receiver-operating characteristic curves of 0.808, 0.832, and 0.791 in the training cohort and 0.836, 0.807, and 0.794 in the testing cohort. Multivariate analysis revealed that the collagen signature could independently predict the disease-free survival (HR = 7.17, p < 0.001) and overall survival rates (HR = 5.03, p < 0.001). The new model had a better prognostic value than the clinicopathological model, which included 4 clinicopathological risk factors: obstruction or perforation, lymphovascular invasion, tumor budding, and no chemotherapy. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: The collagen signature in the tumor microenvironment may be a new prognostic marker that can effectively predict the recurrence and survival of patients with T4N0M0 colon cancer. See Video Abstract at http://links.lww.com/DCR/B503. ASOCIACIÓN DE LA RÚBRICA DE COLÁGENO EN EL MICROAMBIENTE TUMORAL CON LA RECIDIVA Y LA SOBREVIDA DE PACIENTES CON CÁNCER DE COLON T4N0M0: Los factores de riesgo clínico-patológicos actuales no predicen con precisión la recurrencia de la enfermedad en pacientes con cáncer de colon estadío T4N0M0. Presumimos que la rúbrica de colágeno combinada con factores de riesgo clínico-patológicos (nuevo modelo) tendrían un mejor valor pronóstico que los factores de riesgo clínico-patológicos solos (modelo clínico-patológico).El establecer una rúbrica de colágeno en el microambiente tumoral y validar su papel en la predicción de la recidiva del cáncer de colon T4N0M0.Estudio retrospectivo.Investigación llevada a cabo en un centro médico terciario.Se incluyeron pacientes con cáncer de colon T4N0M0 operados en nuestro centro entre 2009 y 2015 (n = 416).Se analizaron un total de 142 características de colágeno en el microambiente tumoral en muestras de cáncer de colon utilizando imágenes de segunda generación armónica. Se construyó una rúbrica de colágeno utilizando un modelo de regresión LASSO Cox.Sobrevida libre de enfermedad y sobrevida global.Las cohortes de entrenamiento y prueba consistieron en 291 y 125 muestras asignadas al azar, con tasas de recurrencia del 19,9% y 22,4%, respectivamente. La rúbrica del colágeno basada en 3 características predijo el riesgo de recurrencia a 1, 3 y 5 años, con el área bajo las curvas características operativas del receptor de 0,808, 0,832 y 0,791 en la cohorte de entrenamiento y 0,836, 0,807 y 0,794 en la cohorte de prueba, respectivamente. El análisis multivariado reveló que la firma de colágeno podría predecir de forma independiente la supervivencia libre de enfermedad (HR = 7,17, p <0,001) y las tasas de sobrevida general (HR = 5,03, p <0,001). El nuevo modelo tuvo un mejor valor pronóstico que el modelo clínico-patológico, que incluyó cuatro factores de riesgo clínico-patológicos: obstrucción o perforación, invasión linfovascular, gemación tumoral y ausencia de quimioterapia.Este estudio estuvo limitado por su diseño retrospectivo.La rúbrica de colágeno en el microambiente tumoral puede ser un nuevo marcador pronóstico para predecir eficazmente la recurrencia y la subrevida de los pacientes con cáncer de colon T4N0M0. Consulte Video Resumen en http://links.lww.com/DCR/B503. (Traducción-Dr. Xavier Delgadillo).

CRLF1-MYH9 Interaction Regulates Proliferation and Metastasis of Papillary Thyroid Carcinoma Through the ERK/ETV4 Axis.

In our previous study, we have shown that CRLF1 can promote proliferation and metastasis of papillary thyroid carcinoma (PTC); however, the mechanism is unclear. Herein, we investigated whether the interaction of CRLF1 and MYH9 regulates proliferation and metastasis of PTC cells via the ERK/ETV4 axis. Immunohistochemistry (IHC), qPCR, and Western blotting assays were performed on PTC cells and normal thyroid cells to profile specific target genes. In vitro assays and in vivo assays were also conducted to examine the molecular mechanism. Results showed that CRLF1 directly bound MYH9 to enhance the stability of CRLF1 protein. Inhibition of MYH9 in PTC cells overexpressing CRLF1 significantly reversed malignant phenotypes, and CRLF1 overexpression activated ERK pathway, in vitro, and in vivo. RNA-sequencing revealed that ETV4 is a downstream target gene of CRLF1, which was up-regulated following ERK activation. Moreover, it was revealed that ETV4 is highly expressed in PTC tissues and is associated with poor prognosis. Finally, the ChIP assays showed that ETV4 induces the expression of matrix metalloproteinase 1 (MMP1) by binding to its promoter on PTC cells. Altogether, our study demonstrates that CRLF1 interacts with MYH9, promoting cell proliferation and metastasis via the ERK/ETV4 axis in PTC.

Primary squamous cell carcinoma (PSCC) of the thyroid: a case report and review of the literature.

Primary squamous cell carcinoma (PSCC) is a rare neoplasm of the thyroid with a very poor prognosis. We report a case of a 42-year-old woman with occasionally found mass in the right anterior area of the neck. After a total thyroidectomy, histopathology and immunohistochemistry tests confirmed primary squamous cell carcinoma of the thyroid with the exclusion of all other possible primary tumor locations. 5 months later, PET scan discovered abnormality in right cervical lymph nodes with a fine needle aspiration confirming to be tumor recurrence. After a modified radical neck dissection was performed with pathological results of the neoplasms being PSCC of the thyroid origin, a full course consecutive radiotherapy was then followed. Due to a prompt diagnosis and the complete dissection of primary tumor and metastatic lymph nodes, no recurrence was observed at the follow-up visits. Comparing to the published cases of PSCC of the thyroid, our paper stated a whole process of diagnosis and standardized treatment, together with classical matched figures of pre-op examinations and dissected specimen. Furthermore, a review of the present literatures summarized the diagnosis, treatment and prognosis of thyroid PSCC. The management of PSCC requires a multi-disciplinary approach.

Lymph node metastasis in suprasternal space in pathological node-positive papillary thyroid carcinoma.

BACKGROUND: The objective of the current study was to investigate the clinical significance of the suprasternal space lymph node (SSLN) in pathological node-positive (pN+) papillary thyroid carcinoma (PTC) patients. METHOD: One hundred and forty patients with pN + PTC who underwent neck dissection were enrolled into this study. SSLN was resected and used as a specimen to investigate the relationship of SSLN with several clinicopathological parameters. RESULTS: The metastasis rate of SSLN was 20.7%. On univariate analysis, we found that SSLN metastasis was significantly associated with primary cancer site (inferior portion), strap muscle invasion, level III metastasis, Level IV metastasis and lymph node metastasis between sternocleidomastoid and sternohyoid muscles. On multivariate analysis, primary cancer site (inferior portion), strap muscle invasion, Level IV metastasis and lymph node metastasis between sternocleidomastoid and sternohyoid muscles were independent risk factors for SSLN metastasis of PTC. CONCLUSION: For pN + PTC patients, special attention should be paid to the issue of SSLN metastasis.

Is Epstein-Barr Virus Infection Associated With Thyroid Tumorigenesis?-A Southern China Cohort Study.

Background: Epstein-Barr virus (EBV) is associated with many epithelial malignancies. A few reports on the association between EBV and thyroid tumorigenesis have been investigated. However, the conclusion is highly contradictory. We aimed to explore the role of EBV in thyroid nodule development and its clinical significance in a cohort from southern China. Method: We conducted a retrospective data abstraction study of patients who underwent thyroidectomy between December 2017 and June 2018. We retrospectively analyzed the clinicopathological parameters and EBV infection status (serological antibodies and in situ hybridization). Result: The cohort comprised 384 patients with newly diagnosed thyroid diseases, including 261 papillary thyroid carcinomas, 87 nodular goiters, 21 follicular adenomas, 12 follicular thyroid carcinomas, and 3 medullary thyroid carcinomas. Forty-two (10.9%) patients were identified as being serological antibody positive. However, there was no association between the clinicopathological parameters and serological antibody positivity. Additionally, none of the patients showed EBER expression in thyroid normal/cancer cell nuclei in in situ hybridization. Conclusion: In this study, no correlation between EBV and thyroid diseases was found in a cohort from southern China.

Treatment-related adverse effects with TKIs in patients with advanced or radioiodine refractory differentiated thyroid carcinoma: a systematic review and meta-analysis.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been administered to advanced or radio-iodine refractory differentiated thyroid carcinoma (RR-DTC) patients for years. We performed a pooled analysis to explore the frequency of severe adverse effects in advanced or RR-DTC patients treated with sorafenib and lenvatinib. METHODS: We performed a comprehensive search of computerized databases, including PubMed, Web of Science, Ovid, EMASE, and the Cochrane Library, from the drugs' inception to July 2018 to identify clinical trials. All grade and severe adverse events (AEs; grade ≥3) were analyzed. This meta-analysis was conducted in accordance with PRISMA guidelines. RESULTS: In total, seve studies published from 2012-2018 with 657 patients were eligible for this study. We included two studies (238 patients) that received 200 mg sorafenib twice and five studies (419 patients) that received 24 mg lenvatinib daily. The frequency of AEs was different among the two drugs. Patients in the sorafenib group had a significantly higher frequency of all grade hand-foot syndrome, hypocalcemia, rash, elevated alanine aminotransferase (ALT), and elevated aspartate aminotransferase (AST). Conversely, the lenvatinib group experienced more frequent all grade voice change, hypertension, nausea, and vomiting compared with those with sorafenib. For grade ≥3 adverse effects, hand-foot syndrome, hypocalcemia, and elevated ALT were more frequent in sorafenib-treated patients. Moreover, lenvatinib-treated patients had a significantly higher incidence of severe weight loss, hypertension, and nausea. CONCLUSION: Significant differences in common adverse effects, such as all-grade and severe AEs, were detected between sorafenib and lenvatinib in the current study. Early intervention and management of treatment-related AEs (TRAEs) can minimize the impact on patients' quality-of-life, and avoid unnecessary dose reductions and treatment-related discontinuations.

The analysis of clinicopathologic predictors of lymph node metastasis and postoperative recurrence in patients with papillary thyroid microcarcinoma from Guangdong Province, China-a multicenter retrospective study.

PURPOSE: Currently the extent of lymph node dissection (LND) for papillary thyroid microcarcinoma (PTMC) remains controversial. The present study aims to investigate the clinicopathologic predictors of lymph node metastasis (LNM) and prognosis in PTMC patients from Guangdong to enable appropriate treatment and follow-up. METHODS: Data including demographics, tumor size, multifocality, extrathyroidal extension (ETE) and concomitant thyroiditis were collected from 374 untreated PTMC patients from Guangdong, China. Univariate and multivariate analyses were performed to identify clinicopathologic predictors of LNM and prognostic indicators in PTMC patients with LNM. RESULTS: During the follow-up period of 120 months, recurrence was significantly higher in patients with LNM than in patients without LNM (P<0.05). Age <45 years, larger tumor (>5 mm) and multifocality were predictors of LNM; age <45 years, larger tumor size and absence of concomitant thyroiditis were associated with central LNM (CLNM); male sex, ETE and multifocality were correlated with lateral LNM (LLNM) (P<0.05). There was no difference in recurrence between patients with CLNM and LLNM (P>0.05). LNM in PTMC primarily influenced disease-free survival. Age >45 years and male sex were risk factors of recurrence in PTMC patients with LNM. Male patients with CLNM and older patients with LLNM exhibited worse prognosis (P<0.05). CONCLUSIONS: PTMC easily metastasizes to cervical lymph nodes, which significantly influences prognosis. Prophylactic LND is recommended in PTMC patients from Guangdong, China, who have a high risk of CLNM and/or LLNM. More aggressive postoperative treatment and more frequent follow-up could be considered for older and/or male PTMC patients with LNM.