Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1α After Treatment: A Cell Regulation Study

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.

Work and lifestyle influencing factors for thyroid cancer among young and middle-aged patients with thyroid nodules / 环境与职业医学

Background The number of persons with thyroid nodules has increased rapidly in recent years, and thyroid cancer caused by malignant nodules has become a key problem endangering the health of young and middle-aged groups in China. Objective To explore work and lifestyle influencing factors for developing thyroid cancer among young and middle-aged patients with thyroid nodules. Methods The subjects with thyroid nodules were reported by routine physical examines ordered at the Huadong Sanatorium. We conducted a 1∶4 matched case-control study in which 232 patients diagnosed with thyroid cancer from 2012 to 2022 were matched to 928 controls by gender and age (±5 years). A validated questionnaire was used to collect data on work and lifestyle behaviors. Univariate and multivariate logistic regression models were applied to explore potential relationships between selected factors (including environment, working hours, stress, diet, exercise, and mental health) and thyroid cancer. Spearman rank correlation was used to analyze the correlations between variables. Results The results of univariate logistic regression showed a history of thyroid cancer reported among first-degree relatives (OR=6.059, 95%CI: 1.007, 36.473), obesity (OR=1.973, 95%CI: 1.296, 3.004), noise and vibration exposure (OR=1.988, 95%CI: 1.143, 3.456), frequent stress (OR=2.093, 95%CI: 1.231, 3.559), frequent depression (OR=2.034, 95%CI: 1.048, 3.947), frequent anger (OR=1.791, 95%CI: 1.066, 3.012), frequent fried food diet (OR=1.535, 95%CI: 1.026, 2.297), and frequent fast food diet (OR=1.836, 95%CI: 1.048, 3.215) were risk factors for reporting thyroid cancer developing from thyroid nodules, while regular meals (OR=0.245, 95%CI: 0.061, 0.989) and frequent exercise (OR=0.571, 95%CI: 0.342, 0.952) were protective factors for reporting no thyroid cancer. The results of Spearman correlation analysis showed that body mass index was positively correlated with frequent fried food, fast food, and sugary beverage diets (r=0.123, 0.083, 0.077, P<0.01), and negatively correlated with frequent depression and anger (r=−0.090, −0.070, P<0.05). The results of multiple logistic regression found that a history of thyroid cancer reported among first-degree relatives (OR=6.712, 95%CI: 1.071, 42.066), obesity (OR=2.032, 95%CI: 1.321, 3.125), noise and vibration exposure (OR=1.991, 95%CI: 1.089, 3.637), and frequent stress (OR=2.468, 95%CI: 1.417, 4.300) were associated with an elevated risk of reporting thyroid cancer developing from thyroid nodules patients. Regular exercise (frequency≥3 times·week−1, > 30 min per episode) (OR=0.516, 95%CI: 0.300, 0.890) was associated with a lowered risk of reporting thyroid cancer. Conclusions Multiple risk factors associated with reporting thyroid cancer among young and middle-aged groups with thyroid nodules are identified, such as obesity, noise and vibration exposure, frequent stress, and lack of exercise.

Accuracy of ultrasound in predicting thyroid malignancy: a comparative analysis of the ACR TI-RADS and ATA risk stratification systems

ABSTRACT Objective: Thyroid nodules are very common in clinical practice, and ultrasound has long been used as a screening tool for their evaluation. Several risk assessment systems based on ultrasonography have been developed to stratify the risk of malignancy and determine the need for fine-needle aspiration in thyroid nodules, including the American Thyroid Association (ATA) system and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). The aim of this study was to compare the performance of the ATA and ACR TI-RADS systems in predicting malignancy in thyroid nodules based on the nodules' final histopathology reports. Materials and methods: We performed a retrospective review of medical records to identify patients who underwent thyroid surgery at King Abdulaziz University from 2017 to 2022. The ultrasound features of the nodules with confirmed histopathology (benign versus malignant) were evaluated. Both ATA and ACR TI-RADS scores were documented. Results: The analysis included 191 patients who underwent thyroid surgery and fulfilled the inclusion criteria. Hemithyroidectomy was performed in 22.5% of the patients, and total thyroidectomy was performed in 77.0% of them. In all, 91 patients (47.6%) were found to have malignant nodules on histopathology. We then compared the histopathology reports with the preoperative ultrasonographic risk scores. The estimated sensitivity and specificity in identifying malignant nodules were, respectively, 52% and 80% with the ATA system and 51.6% and 90% with the ACR TI-RADS system. Conclusion: Both ATA and ACR TI-RADS risk stratification systems are valuable tools for assessing the malignancy risk in thyroid nodules. In our study, the ACR TI-RADS system had superior specificity compared with the ATA system in predicting malignancy among high-risk lesions.

Differentiated thyroid carcinoma: what the nonspecialists needs to know

ABSTRACT Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Coexistence of Hashimoto's thyroiditis and papillary thyroid carcinoma revisited in thyroidology, an experience from an endemic region: fad or future?

SUMMARY OBJECTIVE: Papillary thyroid carcinoma, per se, is the most common type of thyroid cancer, and Hashimoto's thyroiditis is the most frequent autoimmune disease of the papillon gland. The liaison between Hashimoto's thyroiditis and thyroid cancers is still an ongoing debate in thyroidology. The aim of the study was to discuss the frequency of the co-occurrence of Hashimoto's thyroiditis and papillary thyroid carcinoma. METHODS: This study is designed as a retrospective analytical cohort study. The institutional database and archive of histopathology scanning identified the patients who had undergone thyroidectomy between January 2022 and January 2016. The Statistical Package for Social Sciences v21.0 program was used for statistical purposes. Descriptive and chi-square tests were applied, and a p<0.05 was considered significant. RESULTS: Of 498 patients who had undergone thyroidectomy for 4 years, 99 (20%) were male and 399 (80%) were female. Of note, papillary thyroid carcinoma was revealed in 160 (32%) patients, and Hashimoto's thyroiditis was recognized in 178 (35.74%) patients. The prevalence of Hashimoto's thyroiditis in cases with papillary thyroid carcinoma was 43.8%, while the prevalence in patients with Hashimoto's thyroiditis was 41.1%. CONCLUSION: A debate still remains on the propriety of these two phenomena. Herewith, we recognized a correlation between the presence of papillary thyroid carcinoma and Hashimoto's thyroiditis. Providers should be vigilant about the coexistence of these phenomena. We might postulate the so-called total thyroidectomy for cases with a cytologic diagnosis of Hashimoto's thyroiditis with a papillary thyroid carcinoma. As a matter of fact, this issue merits further investigation.

Experiencia en cirugía de tiroides en el Hospital Oncológico Conrado Benítez de Santiago de Cuba / Thyroid Surgery Experience at Hospital Oncológico Conrado Benítez of Santiago de Cuba

Introducción: Los nódulos de tiroides son un problema clínico común. La tiroidectomía es una de las técnicas más realizadas en los servicios de cabeza y cuello y constituye un tratamiento con intención curativa en el cáncer de tiroides y afecciones benignas como el bocio nodular y el adenoma. Objetivo: Describir la experiencia en cirugía de tiroides del servicio de cabeza y cuello en el Hospital Oncológico Conrado Benítez. Métodos: Se realizó un estudio descriptivo, longitudinal y prospectivo de los pacientes que recibieron algún tratamiento quirúrgico por enfermedad tiroidea en el período comprendido entre el 1 de septiembre de 2017 y el 31 de agosto de 2022. Resultados: El 87 por ciento de los pacientes eran mujeres, con una edad media de 47,1 años. A todos se les realizó ecografía y biopsia por aspiración con aguja fina con una estrecha concordancia con el diagnóstico definitivo. Predominó el carcinoma papilar (39,5 por ciento), la tiroidectomía total como técnica más empleada (86,5 por ciento) y el 94,6 por ciento de los pacientes no tuvo complicaciones. La lesión recurrencial solo estuvo presente en el 1,1 por ciento de los casos. Conclusiones: La experiencia en tiroidectomía en el Hospital Oncológico Conrado Benítez es buena, con una concordancia entre medios diagnósticos y biopsia definitiva, tiempo quirúrgico adecuado y pocas complicaciones(AU)

Introduction: Thyroid nodules are a common clinical problem. Thyroidectomy is one of the most performed techniques in head and neck surgery services, as well a treatment with curative intent for thyroid cancer and benign conditions such as nodular goiter and adenoma. Objective: To describe the experience in thyroid surgery at the head and neck surgery service from Hospital Oncológico Conrado Benítez. Methods: A descriptive, longitudinal and prospective study was carried out with patients who received any surgical treatment for thyroid disease in the period from September 1, 2017 to August 31, 2022. Results: 87 percent of patients were female, with a mean age of 47.1 years. All of them underwent ultrasonography and fine-needle aspiration biopsy, presenting a close concordance with their definitive diagnosis. Papillary carcinoma predominated (39.5 percent), total thyroidectomy was the most commonly used technique (86.5 percent) and 94.6 percent of patients had no complications. Any recurrent lesion was present in only 1.1 percent of cases. Conclusions: The thyroidectomy experience at Hospital Oncológico Conrado Benítez is good, based on the concordance between diagnostic means and definitive biopsy, as well as adequate surgical time and few complications(AU)

Clinical and histopathological features of follicular thyroid cancer in Chile

ABSTRACT Objective: Follicular thyroid carcinoma (FTC) is less frequent but has a worse prognosis than papillary carcinoma. The available evidence on pre-operative characteristics of FTC is controversial. Our objective was to characterize the clinical, ultrasound and histopathological presentation of FTC patients treated Chile. Subjects and methods: Retrospective analysis of 97 patients treated for FTC in 6 large centers in Chile. We analyzed their ultrasonographic features and classified the nodules according to ATA risk of malignancy and TI-RADS score, as well as the cytological findings according to the Bethesda system. We described their clinical and histopathological findings at diagnosis and classified their risk of recurrence and mortality according to ATA 2015 recurrence risk category and the eighth edition of the AJCC/UICC staging system, respectively. Results: Median age was 48 years and 73.2% were females. The median diameter was 38.8 mm; only 9.5% of them were microtumors. According to ATA risk of malignancy, 86% of the nodules were low or intermediate suspicious, while 78% were category 3 or 4A nodules according to the TI-RADS. Regarding the Bethesda system, 65.9% had indeterminate cytology (20.6% category III and 45.3% category IV). At histological examination, most were minimally-invasive and angio-invasive tumors with less than 4 foci (54.7% and 28.4% respectively). More than 90% of FTC were unifocal and there was no lymphovascular or extrathyroidal invasion or lymph node involvement. Four patients (4.1%) had distant metastases at diagnosis. Most patients (95%) had stage I or II disease according to the AJCC/UICC staging system, while the risk of recurrence was low at 51.5% when using the ATA risk of recurrence scale. Conclusions: At diagnosis, most FTCs were nodules of low or intermediate suspicion at ultrasound, nearly two thirds had indeterminate cytology according to the Bethesda system, and nearly 50% of them were of low risk of recurrence.

Rehabilitación del nervio recurrente laríngeo postiroidectomía / Recurrent laryngeal nerve rehabilitation after thyroidectomy

El carcinoma papilar tiroideo es el tipo de cáncer más común de esta glándula, y su tratamiento de elección es la tiroidectomía. Entre las complicaciones asociadas resalta la parálisis de las cuerdas vocales, la cual ocurre por una lesión directa del nervio laríngeo recurrente durante la cirugía. Se presenta una paciente de 22 años de edad con este diagnóstico, a la cual se le realizó una tiroidectomía total; en el postoperatorio inmediato la paciente comenzó con estridor laríngeo intenso que requirió una traqueotomía de urgencia. En el examen físico se constató una parálisis bilateral de las cuerdas vocales y se decidió comenzar un tratamiento de rehabilitación del nervio recurrente laríngeo con laserterapia y HIVAMAT-200 como modalidades combinadas. Los resultados alcanzados con la fisioterapia fueron satisfactorios y la paciente se reintegró rápidamente a su ámbito familiar, escolar y social.

Papillary thyroid carcinoma is the most common type of cancer of this gland, and its treatment of choice is thyroidectomy. Vocal cord paralysis stands out among the associated complications, in which a direct injury to the recurrent laryngeal nerve occurs during surgery. We present a 22-year-old female patient with this diagnosis, who underwent a total thyroidectomy; in the immediate postoperative period the patient began with intense laryngeal stridor requiring an emergency tracheotomy. Physical examination revealed bilateral vocal cord paralysis and it was decided to begin rehabilitation treatment of the recurrent laryngeal nerve with laser therapy and HIVAMAT-200 as combined modalities. The results achieved with physiotherapy were satisfactory and the patient was quickly reintegrated into her family, school and social environment.

Risk Factors for Malignancy in Patients with Multinodular Goiter

Abstract Introduction The identification of thyroid cancer may be conducted through clinical detection, imaging method, and histopathological examination. Both solitary nodules and multinodular goiter are associated with malignancy. Objective To assess the risk factors for malignancy among patients with multinodular goiter submitted to total thyroidectomy. Methods A series of 712 consecutive patients, submitted to total thyroidectomy between 2005 and 2016 with multinodular goiter regarding clinical, ultrasound, and pathological variables, was retrospectively evaluated. Results There were 408 cases of papillary carcinoma (57.3%), with the remaining being benign. Gender had no statistical significance (p = 0.169) for malignancy, unlike the Bethesda index, higher age group (p = 0.005), shorter clinical history time (p = 0.036), smaller number of nodules (p < 0.0001), and smaller nodule size (p < 0.0001), which were related to malignancy. Conclusion The Bethesda index, older age group, shorter clinical history, smaller number of nodules, and smaller size of nodule were related to the diagnosis of papillary carcinoma.

LncRNA MCM3AP-AS1 serves as a competing endogenous RNA of miR-218 to upregulate GLUT1 in papillary thyroid carcinoma

ABSTRACT Objective: MCM3AP-AS1 has been characterized as an oncogenic long non-coding RNA (lncRNA) in several cancers including papillary thyroid cancer (PTC), but its role in PTC has not been fully elucidated. Considering the critical role of lncRNAs in cancer biology, further functional analysis of MCM3AP-AS1 in PTC may provide novel insights into PTC management. Subjects and methods: Paired tumor and non-tumor tissues were collected from 63 papillary thyroid carcinoma (PTC) patients. Expression levels of MCM3AP-AS1 , miR-218 and GLUT1 in tissue samples were analyzed by qRT-PCR. Cell transfection was performed to explore the interactions among MCM3AP-AS1 , miR-218 and GLUT1 . Cell proliferation assay was performed to evaluate the effects of MCM3AP-AS1 and miR-218 on cell proliferation. Results: MCM3AP-AS1 accumulated to high levels in PTC tissues and was affected by clinical stage. MCM3AP-AS1 showed a positive correlation with GLUT1 across PTC tissues. RNA interaction prediction showed that MCM3AP-AS1 could bind to miR-218 , which can directly target GLUT1 . MCM3AP-AS1 and miR-218 showed no regulatory role regulating the expression of each other, but overexpression of MCM3AP-AS1 upregulated GLUT1 and enhanced cell proliferation. In contrast, overexpression of miR-218 downregulated GLUT1 and attenuated cell proliferation. In addition, miR-218 suppressed the role of MCM3AP-AS1 in regulating the expression of GLUT1 and cell proliferation. Conclusions: MCM3AP-AS1 may serve as a competing endogenous RNA of miR-218 to upregulate GLUT1 in PTC, thereby promoting cell proliferation. The MCM3AP-AS1/miR-218/GLUT1 pathway characterized in the present study might serve as a potential target to treat PTC.

Distribución mutación BRAFsegún carac-terísticas epidemiológicas e histopatológicas en cáncer papilar de tiroides. Un estudio observacional de centro único / BRAFmutation distribution according to epidemiological and histopathological characteristics in papillary thyroid cancer patients. A single-center observational study

Introducción: El cáncer de tiroides se posiciona como una de las neoplasias más prevalentes en Ecuador, manifestándose típicamente en la cuarta década de vida, con una mayor inciden-cia en mujeres. El subtipo histológico predominante es el papilar (CPT), y diversos estudios han evidenciado que hasta un 80% de los casos de CPT presentan la mutación BRAF. Esta mutación se ha asociado con factores de pronóstico desfavorable, como la presencia de me-tástasis ganglionares, estadíos tumorales avanzados, extensión extratiroidea y característi-cas histológicas agresivas. Además, se ha observado una relación con una mayor tasa de recurrencia y una respuesta reducida al tratamiento con yodo. Ante este contexto, esta inves-tigación se propone analizar la distribución de la mutación BRAF según características epide-miológicas e histopatológicas en pacientes con diagnóstico de cáncer papilar de tiroides en Ecuador. Materiales y métodos: Este estudio se llevó a cabo de manera descriptiva y retrospectiva, abarcando a pacientes con diagnóstico de cáncer papilar de tiroides a quienes se les practicó el análisis genético para la detección de la mutación BRAF. La muestra incluyó 106 historias clínicas que cumplían con los criterios de selección establecidos Resultados: La evaluación de las historias clínicas reveló la presencia de la mutación BRAF en el 75% de los casos. Este porcentaje fue más elevado en mujeres, individuos mayores de 45 años y residentes en áreas urbanas. Respecto a la ocupación, la mayoría de los pacientes se dedicaba a labores de limpieza y no presentaban antecedentes personales de exposición a radiación ionizante ni antecedentes oncológicos familiares. El 84% se encontraba en la etapa clínica I, y en su mayoría, la neoplasia estaba localizada en el lóbulo tiroideo derecho.Conclusión:Este análisis subraya la imperiosa necesidad de identificar los factores de riesgo vinculados con la aparición del carcinoma papilar de tiroides en la población ecuatoriana. Los resultados indican una prevalencia significativa de la mutación BRAF, lo que subraya su rele-vancia comomarcador pronóstico en esta enfermedad. Estos hallazgos pueden contribuir a una mejor comprensión de la epidemiología y la patogenia del cáncer de tiroides, así como a la mejora de las estrategias de prevención y tratamiento en el ámbito local.

Introduction: Thyroid cancer is positioned as one of the most prevalent neoplasms in Ecuador, typically manifesting in the fourth decade of life, with a higher incidence in women. The pre-dominant histological subtype is papillary carcinoma (PTC), and various studies presentshown that up to 80% of PTC cases present the BRAF mutation. This mutation has been as-sociated with unfavorable prognostic factors, such as the presence of lymph node metasta-ses, advanced tumor stages, extrathyroidal extension, and aggressive histologicalfeatures. Additionally, a correlationhas been observed with a higher recurrence rate and a reduced re-sponse toiodine treatment. Given this context, this research aims to analyze the distribution of the BRAF mutation according to epidemiological and histopathological characteristics in patients diagnosed with papillary thyroid cancer in Ecuador. Materials and methods: This retrospective descriptive study involved the analysis of genetic data from 106 medical records of patients diagnosed with papillary thyroid cancer who under-went BRAF mutation detection. The sample was selected based on established criteria. Results: Evaluation of medical records revealed the presence of the BRAF mutation in 75% of cases. This percentage was higher in women, individuals over 45 years of age, and residents in urban areas. Regarding occupation, most patients were dedicated to cleaning work and had no personal history of exposure to ionizing radiation orafamily history of cancer.Additionally, 84% of the patients were in clinical stage I and the neoplasmswerelocated in the right thyroid lobe.Conclusion: This analysis highlights the urgent need to identify risk factors linked to the ap-pearance of papillary thyroid carcinoma in the Ecuadorian population. The results indicate a significant prevalence of the BRAF mutation, underlining its relevance as a prognostic marker in this disease. These findings may contribute to a better understanding of the epidemiology and pathogenesis of thyroid cancerleadingtoimprovementsinprevention and treatment strategies at the local level.

Meta-analysis of efficacy and safety of cabozantinib in the treatment of advanced thyroid cancer / 中国药房

OBJECTIVE To review the efficacy and safety of cabozantinib in the treatment of advanced thyroid cancer. METHODS Retrieved from PubMed， the Cochrane Library， Embase， ClinicalTrials.gov， Wanfang data， VIP， CNKI and China Clinical Trials Registry， randomized controlled trials （RCTs） about cabozantinib （trial group） versus placebo （control group） were collected from the inception to Nov. 2022. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 4 RCTs were included involving 588 patients. The results of the meta-analysis showed that the progression free survival （PFS） [HR＝0.24， 95%CI （0.19，0.31）， P＜0.000 01]， objective response rate （ORR） [RR＝31.46， 95%CI （6.32，156.75）， P＜0.000 1]， the incidence of grade 3-4 adverse event （AE） [RR＝2.15，95%CI （1.76，2.61），P＜0.000 01]， severe adverse event [RR＝1.78，95%CI （1.11，2.83），P＝0.02]， diarrhea [RR＝3.29，95%CI（1.62， 6.66），P＝0.001]， palmar-plantar erythrodysesthesia syndrome [RR＝28.19，95%CI （12.25，64.88），P＜0.000 01]， and hypertension [RR＝6.50，95%CI （3.90，10.83），P＜0.000 01] in trial group were significantly higher than control group； there was no statistical significance in overall survival （OS） [HR＝0.83，95%CI （0.67，1.02）， P＝0.07] or the incidence of fatigue [RR＝1.25，95%CI （0.78，1.98），P＝0.35] between the two groups. Subgroup analysis showed that PFS and ORR in patients with differentiated thyroid carcinoma （DTC） and medullary thyroid carcinoma （MTC） in the trial group were significantly higher than control group （P＜ 0.05）. There was no significant difference in OS of DTC and MTC patients in the trial group compared with the control group （P＞ 0.05）. CONCLUSIONS Cabozantinib can prolong PFS and increase ORR in patients with advanced thyroid cancer， but the incidence of AE is high.

Risk factors of central compartment lymph node metastasis in stage T 1a solitary papillary thyroid carcinoma / 肿瘤研究与临床

Objective:To investigate the correlation of central compartment lymph node metastasis(CLNM) in stage T 1a solitary papillary thyroid carcinoma (PTC) with the clinicopathological characteristics, sonographic features and the number of lymph node dissection, and to analyze the risk factors of CLNM. Methods:The data of 218 patients with stage T 1a solitary PTC who underwent thyroid cancer surgery from January 2017 to May 2021 in Tangshan Union Medical College Hospital were retrospectively analyzed. All patients were divided into CLNM positive group and CLNM negative group according to CLNM. The age, gender, preoperative sonographic features, pathological type, the number of lymph node dissection and the number of metastasis were recorded. Logistic regression was used to analyze the risk factors of CLNM. Results:Among 218 patients, there were 71 cases (32.6%) in CLNM positive group and 147 cases (67.4%) in CLNM negative group. There were statistically significant differences in age, tumor diameter, capsular invasion in thyroid or not, tumor blood supply or not, and the number of lymph node dissection between two groups (all P < 0.05). There were no statistically significant differences in gender, clear tumor boundary or not, tumor shape, tumor aspect ratio, calcification, nodular goiter and Hashimoto's thyroiditis or not (all P > 0.05). Multivariate binary logistic regression analysis showed that age < 55 years ( OR = 2.995, 95% CI 1.228-7.307), capsular invasion in thyroid ( OR = 5.297, 95% CI 2.494-11.248) and the number of lymph node dissection ≥6 ( OR = 4.085, 95% CI 2.059-8.104) were independent risk factors of CLNM (all P < 0.05). Conclusions:Patients with stage T 1a solitary PTC, age < 55 years and capsular invasion in thyroid are prone to CLNM; sufficient number of lymph node dissection can get more accurate CLNM rate.

Expressions of serum thyroid stimulating hormone, thyroid peroxidase antibody and thyroglobulin antibody in papillary thyroid carcinoma and their clinical significances / 肿瘤研究与临床

Objective:To explore the relationship between serum levels of thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) and the development of papillary thyroid carcinoma.Methods:The clinical data of 574 patients with thyroid nodules who received surgical treatment in Tengzhou Central People's Hospital from January to December 2021 were retrospectively analyzed. Using histopathological diagnosis as the gold standard, the patients were divided into papillary thyroid carcinoma group (malignant group, 267 cases) and benign thyroid nodules group (benign group, 307 cases). The clinical data and the preoperative serum TSH, TPO-Ab and Tg-Ab levels were compared between the two groups. The correlation between preoperative serum TSH, TPO-Ab and Tg-Ab levels and papillary thyroid cancer was analyzed by logistic regression.Results:There were no statistical differences in the age and gender of patients between the malignant group and the benign group (all P > 0.05). TSH [2.37 mIU/L (1.43 mIU/L, 5.09 mIU/L)], TPO-Ab [17.84 IU/ml (11.94 IU/ml, 40.68 IU/ml)] and Tg-Ab [15.69 IU/ml (10.57 IU/ml, 132.00 IU/ml)] in the malignant group were higher than those in the benign group [TSH 1.60 mIU/L (0.88 mIU/L, 2.57mIU/L), TPO-Ab 14.29 IU/ml (10.00 IU/ml, 21.17 IU/ml), Tg-Ab 12.23 IU/ml (10.00 IU/ml, 16.51 IU/ml)], and the differences were statistically significant ( Z values were -6.43, -4.60 and -6.15, all P < 0.05). Multivariate logistic regression analysis showed that positive TPO-Ab ( OR = 0.996, 95% CI 0.993-0.999, P = 0.013) and positive Tg-Ab ( OR = 0.996, 95% CI 0.994-0.998, P < 0.05) were independent risk factors for papillary thyroid cancer. Conclusions:Preoperative serum TSH, TPO-Ab and Tg-Ab levels are closely related to papillary thyroid cancer, among which positive serum TPO-Ab and positive Tg-Ab are independent risk factors for papillary thyroid cancer and have important values in the differential diagnosis of benign and malignant thyroid nodules.

Synergistic mechanisms of ferroptosis in anaplastic thyroid cancer induced by dihydroartemisinin and sorafenib / 中华内分泌代谢杂志

Objective:To investigate the synergistic effects and molecular mechanisms of dihydroartemisinin(DHA) and sorafenib(SOR) in inducing ferroptosis in anaplastic thyroid cancer(ATC) cells.Methods:CCK-8 and flow cytometry assays were performed to detect the effects of DHA and SOR on the proliferation and ferroptosis of ATC cells(CAL-62). Real-time fluorescence quantitative PCR and Western blotting assays were performed to detect the expressions of ferroptosis-related genes glutathione peroxidase 4(GPX4), solute carrier family 7 member 11 gene(SCL7A11), lipoxygenase-15(LOX-15), and p53. The levels of iron death intermediate metabolites including lactate dehydrogenase(LDH), glutathione(GSH), malondialdehyde(MDA), ferrous ion(Fe 2+ ), nitric oxide(NO), and reactive oxygen species(ROS)were measured by corresponding assay kits. The corresponding inhibition of DHA and SOR on ATC in vivo was analyzed in a tumor model in nude mice. Results:Compared with the control group, DHA, SOR, and DHA+ SOR treatment significantly inhibited cell proliferation and apoptosis in a dose-dependent manner( P<0.001), with increased LDH, Fe 2+, MDA, and ROS contents and reduced GSH activity( P<0.001), which were promoted by ferrous sulfate(FeSO 4)and reversed by ferroptosis inhibitor-1. Compared with the control group and the drug monotherapy group, 15-LOX-2 and p53 expressions were upregulated in DHA+ SOR group while GPX4 and SCL7A11 expressions were decreased( P<0.001), without significant difference in 15-LOX-1 protein content. In addition, NO level was significantly increased in DHA+ SOR group( P<0.001). DHA and SOR inhibited tumor growth of ATC in vivo. Conclusion:DHA and SOR synergistically induced ferroptosis via upregulating the expression of 15-LOX-2 gene and inhibiting NO synthesis in ATC cells.

Research status of combined gene mutations in anaplastic thyroid cancer / 中华内分泌代谢杂志

Anaplastic thyroid cancer (ATC) is the most malignant thyroid cancer with a low incidence but high mortality. ATC is highly aggressive, rapidly progressing, and has poor prognosis. Current treatment options is not efficacious, so there is an urgent need to investigate its pathogenesis to update the treatment and improve the survival rate. Previous studies have found that most ATC can develop from well-differentiated thyroid cancer, and BRAF and RAS mutations are the key driving factors of ATC. TP53, PI3K pathway, PTEN, TERT, SWI/SNF complex Subunit, NF2 and other mutations also play an important role in the occurrence of ATC. Recent studies have found that single gene mutation is often not sufficient to drive the occurrence of ATC, and ATC is usually developed from the accumulation of multiple mutations in well-differentiated thyroid cancer. Therefore, this paper reviews the role of common combined mutations in ATC, deepens the understanding of the pathogenesis, and provides a basis for finding effective therapeutic targets.

Efficacy of routine exposure versus neuromonitoring of superior laryngeal nerve in thyroid cancer surgery / 中国基层医药

Objective:To investigate the efficacy of routine exposure versus neuromonitoring of the external branch of the superior laryngeal nerve (EBSLN) in thyroid cancer surgery. Methods:The clinical data of 500 patients who underwent open thyroid cancer surgery in the Department of Breast and Thyroid Surgery, People's Hospital of Quzhou from July 2017 to June 2020 were retrospectively analyzed. These patients were divided into a monitoring group ( n = 300) and an unmonitored group (control group) ( n = 200) according to whether neuromonitoring was performed during surgery. In the control group, the EBSLN was routinely exposed during the surgery for naked observation. In the monitoring group, the EBSLN was monitored. The Voice Handicap Index score, vocal cord function, and serum levels of parathyroid hormone and calcium ion were compared between the two groups before and after surgery. All patients were followed up for 1 year to observe injury to the EBSLN, parathyroid gland injury, and hypocalcemia. Results:In the monitoring group, operative time (112.32 ± 10.42) minutes, intraoperative blood loss (10.58 ± 5.04) mL, time to extubation (2.07 ± 0.54) days, postoperative drainage flow (10.55 ± 3.58) mL, and postoperative hospital stay (3.03 ± 1.03) days were significantly shorter and less compared with the control group ( t = 18.68, 15.09, 15.24, 32.98, 27.37, all P < 0.001). Compared with before surgery, normalized noise energy, amplitude perturbation, fundamental frequency perturbation, and fundamental frequency value in each group were significantly decreased after surgery, harmonic to noise ratio and the Voice Handicap Index were significantly increased after surgery. These indices were more obviously improved in the monitoring group compared with the control group ( t = 43.31, 27.10, 46.45, 37.11, 8.97, all P < 0.001). Compared with before surgery, serum levels of parathyroid hormone and calcium ion in each group were significantly decreased after surgery. After surgery, serum levels of parathyroid hormone and calcium ion in the control group were significantly lower than those in the monitoring group ( t = 41.14, 5.99, both P < 0.001). The incidence of complications in the monitoring group [4 cases of hypocalcemia (1.33%), 0 cases of parathyroid injury (0.00%), 8 cases of injury to the EBSLN] was significantly lower than that in the control group ( χ2 = 73.41, 74.17, 76.29, all P < 0.001). Conclusion:Neuromonitoring of the EBSLN during open thyroid cancer surgery can effectively improve patient voice and vocal cord function, reduce the rate of injury to the EBSLN, and has a clinical application value.

Research progress on the influence of iodine nutritional status on biomarkers of thyroid cancer / 中华地方病学杂志

Thyroid cancer is one of the common malignant tumors in the endocrine system, and its incidence is increasing year by year. At present, the main diagnostic methods for thyroid cancer are ultrasound and thyroid puncture cytology. However, due to low sensitivity and/or specificity, it is increasingly difficult to meet the current clinical diagnostic needs. The discovery of biomarkers in thyroid cancer provides important clues for the diagnosis, pathogenesis and prognosis of the disease. As one of the essential trace elements in human body, iodine is closely related to the thyroid gland. Clarifying the relationship between iodine nutritional status and biomarkers of thyroid cancer has important practical significance for the diagnosis, pathogenesis and prognosis of thyroid cancer. Based on the research of systems biology, this article analyzes the influence of iodine nutritional status on biomarkers of thyroid cancer from four aspects of gene, transcription, protein and metabolism,

Nomogram based on clinical, ultrasonic and BRAF V600E gene for predicting cervical lymph node metastasis in patients with papillary thyroid carcinoma / 中国医师进修杂志

Objective:To Constructing a nomogram based on clinical, ultrasound and BRAF V600E gene for predicting cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC).Methods:The clinical data of 287 patients with PTC (374 malignant nodules) from December 2019 to December 2021 in the First Affiliated Hospital of Hunan Normal University were analyzed retrospectively. Among them, there were 205 nodes with cervical lymph node metastasis and 169 nodes without cervical lymph node metastasis. The echo type, capsule, boundary, shape, number, diameter, location, cystic and solid properties, aspect ratio, blood flow signal, echo distribution, ultrasonic classification, microcalcification and enlarged lymph nodes were observed by ultrasound. The mutation of BRAF V600E gene was detected by fluorescence polymerase chain reaction. The nomograph model for predicting neck lymph node metastasis in patients with PTC was constructed and validated by R3.6.3 software.Results:Univariate analysis result showed that gender, age, microcalcifications, aspect ratio, morphology, blood flow signal, diameter, echo distribution, enlarged lymph nodes, ultrasound classification and BRAF V600E gene were the risk factors for cervical lymph node metastasis in patients with PTC ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that age (<40 years old), ultrasonic classification (≥4a) and diameter (>1 cm) were independent risk factors for cervical lymph node metastasis in patients with PTC ( OR = 2.847, 1.436 and 2.475; 95% CI 1.827 to 4.436, 1.075 to 1.918 and 1.505 to 4.069; P<0.01 or <0.05). The age, ultrasonic classification and diameter were included as predictors for constructing the nomogram model. The receiver operating characteristic curve analysis result shows that the area under the curve predicted by the nomogram model for neck lymph node metastasis in patients with PTC was 0.692 (95% CI 0.631 to 0.753). Conclusions:Nomogram based on age, ultrasonic classification and diameter is of high value in predicting neck lymph node metastasis in patients with PTC.

Effects of discontinuation of levothyroxine sodium before radioactive iodine therapy after DTC on blood lipids and renal function in patients / 中华内分泌外科杂志

Objective:To investigate the effect of levothyroxine withdrawal before radioiodine therapy on blood lipids and renal function in patients with differentiated thyroid carcinoma (DTC) after operation.Methods:From Mar. 2020 to Apr. 2022, 214 patients with differentiated thyroid cancer were enrolled in the General Surgery Department, Linyi Central Hospital, Shandong Province. All patients stopped taking levothyroxine sodium after total thyroidectomy. The thyroid function index, blood lipid index and renal function index were measured and compared before and after drug withdrawal (before operation) and after drug withdrawal (before radioiodine treatment). The patients were divided into groups according to the duration of drug withdrawal (drug withdrawal group for 3 weeks, drug withdrawal group for 4 weeks), and the differences of thyroid function index, blood lipid index, and renal function index among patients with different drug withdrawal time were compared. The measurement data in accordance with normal distribution were compared between groups, and independent sample t-test was performed. Results:The levels of free thyroxin T4 (FT 4) and free triiodothyronine (FT 3) in DTC patients decreased significantly ( t=57.60, 71.74,all P<0.001), and the levels of thyroid-stimulating hormone (TSH) increased significantly ( t=102.15, P<0.001). After drug withdrawal, the serum lipid index [triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low density lipoprotein (LDL) ] and renal function index [blood urea nitrogen (BUN), serum creatinine (SCR) ] of DTC patients increased significantly ( t=20.17, 42.50, 12.13, 30.73, 16.09, 43.73, all P<0.001). The levels of FT 3 and FT 4 in the 4-week group were significantly lower than those in the 3-week group ( t=7.75 and 10.07, both P<0.001), and TSH was significantly higher than that in the 3-week group ( t=26.46, P<0.001). The levels of TG, LDL, HDL, TC, BUN and Scr in the 4-week group were significantly higher than those in the 3-week group ( t=10.13, 10.29, 8.53, 11.47, 10.54, 8.55, all P<0.001). Correlation analysis showed that the levels of FT 3 and FT 4 in DCT patients were negatively correlated with the levels of TG, LDL, HDL, TC, BUN and Scr ( r=-0.256, -0.189, -0.249, -0.314, -0.352, -0.231, -0.342, -0.259, -0.304, -0.216, -0.391, -0.271, P=0.011, 0.029, 0.007, 0.004, 0.015, 0.036, 0.002, 0.009, 0.019, 0.017, 0.016, 0.003), and the levels of TSH were correlated with TG, LDL, HDL, TC and BUN Scr level was positively correlated ( r=0.257, 0.308, 0.219, 0.311, 0.251, 0.271, P=0.006, 0.013, 0.032, 0.004, 0.006, 0.014) . Conclusion:Stopping levothyroxine sodium before radioactive iodine treatment after DTC can easily lead to dyslipidemia and decreased renal function in patients, and the longer the withdrawal time is, the more obvious the changes of blood lipids and renal function in patients, and the withdrawal time should be shortened in clinical treatment.