Experiencia en cirugía de tiroides en el Hospital Oncológico Conrado Benítez de 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 % 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 %), la tiroidectomía total como técnica más empleada (86,5 %) y el 94,6 % de los pacientes no tuvo complicaciones. La lesión recurrencial solo estuvo presente en el 1,1 % 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.

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 % 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 %), total thyroidectomy was the most commonly used technique (86.5 %) and 94.6 % of patients had no complications. Any recurrent lesion was present in only 1.1 % 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.

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.

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,

Research advances in radiation exposure and the risk of thyroid cancer / 中国辐射卫生

The thyroid gland is highly sensitive to the carcinogenic effects of radiation exposure during childhood and adolescence. Epidemiological data have shown that exposure to ionizing radiation during childhood and adolescence results in an increased risk of thyroid cancer, and most cases of radiation-induced thyroid cancer are diagnosed with papillary thyroid carcinoma. The risk of radiation-induced thyroid cancer is affected by radiation dose, age, latency period, iodine status, chemotherapy, and body mass index. Therefore, proper use of physical shielding and prompt administration of stable iodine can be adopted to minimize the risk of radiation-induced thyroid cancer.

Evaluation of the therapeutic effect of deuterium depleted water on gastroenteritis induced by 131I radiation in thyroid cancer treatment / 中国辐射卫生

Objective To investigate the therapeutic effect of oral administration of deuterium depleted water on gastroenteritis induced by 131I radiation in thyroid cancer treatment. Methods Fifty patients with papillary thyroid cancer treated with 131I in the Department of Nuclear Medicine of Changshu No.2 People’s Hospital from May 2022 to February 2023 were divided into control group and experimental group (25 patients in each group). Data were continuously collected throughout the study duration. The control group was orally administrated omeprazole enteric-coated capsules and purified water at 660 mL tid for 5 days. The experimental group received the same basic treatment as the control group except that deuterium depleted water was used instead of purified water. The incidence and alleviation of 131I radiation-induced gastroenteritis were observed and compared between the two groups using the Fisher’s exact test and Kaplan-Meier analysis. Results The number of gastroenteritis cases from day 1 to day 5 after 131I administration was 2 (8%), 5 (20%), 2 (8%), 1 (4%), and 0 (0%), respectively, in the experimental group, and 2 (8%), 8 (32%), 4 (16%), 3 (12%), and 1 (4%), respectively, in the control group. The incidence of gastroenteritis was significantly different between the two groups (χ2=4.064, P=0.044). After 5 days of treatment, the overall response rate of patients in the experimental group was 96%, which was significantly higher than 76% in the control group (χ2=9.105, P=0.025). Conclusion Oral administration of deuterium depleted water is effective in the relief of clinical symptoms of 131I radiation-induced gastroenteritis in thyroid cancer treatment. The clinical application of deuterium depleted water should be further investigated.

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.

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.

Value of monitoring serum t-PINP/β-CTX ratio and 25 (OH) D levels in the prevention and treatment of osteoporosis after surgery for differentiated thyroid cancer in elderly women / 中华内分泌外科杂志

Objective:To investigate the level change of serum total n-terminal propeptide of type Ⅰ precollagen (t-PINP) /type Ⅰ collagen carboxy-terminal peptide (beta-CTX) ratio, 25-hydroxyvitamin D (25-hydroxyvitamin D, 25 (OH) ) ratio, and 25-hydroxyvitamin D in elderly women with differentiated thyroid cancer (DTC) after surgery and its value in the prevention and treatment of osteoporosis (OP) .Methods:From Jan. 2020 to May. 2021, 112 elderly female postoperative DTC patients treated with thyroid stimulating hormone (TSH) suppression in Department of Endocrinology of Wenzhou Hospital of Integrative Medicine were collected for a prospective study, and the incidence of OP after 1 year of treatment was counted, and according to the incidence of OP, they were divided into incidence group ( n=78) and non-incidence group ( n=34). The general information, thyroid parameters [TSH, free triiodothyronine (FT3), free thyroxine (FT4) ], bone mineral density (BMD), and serum t-titrosine (BMD) were compared between the two groups. SPSS22.0 software was used, and the counting data was described by examples χ2 test. Grade data was expressed in u, Ridit test was used, measurement data was described in mean±standard deviation ( ±s), t test was used, Pearson correlation coefficient model was used to analyze postoperative thyroid index and serum t-PINP/β- Correlation between CTX ratio and 25 (OH) D level, and serum t-PINP after 1 year of treatment was analyzed through interaction/β- The role of CTX ratio and 25 (OH) D level in OP occurrence. Results:The incidence of OP after 1 year of TSH suppression treatment in 112 elderly female post-DTC patients in this study was 69.64% (78/112) ; serum TSH levels (0.63±0.19) mIU/ml after 1 year of treatment in patients who developed OP were lower than those in patients who did not develop OP (0.81±0.22) mIU/ml, and serum FT3 (6.15±1.71) pmol/ml and FT4 levels (24.63±4.28) pmol/ml were higher than those of patients without OP (4.32±1.29) pmol/ml and (20.36±3.70) pmol/ml ( t1=4.391, t2=5.581, t3=5.050,all P<0.05) .Serum t-PINP/β-CTX ratio (130.27±18.09) and 25 (OH) D level (20.18±4.15) ng/ml after 1 year of treatment in patients with OP were lower than those in patients without OP (148.56±20.37) and (23.36±4.36) ng/ml ( t1=4.733, t2=3.672, both P<0.05) ; serum TSH levels were positively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels, and serum FT3 and FT4 levels were negatively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels after 1 year of treatment in patients with OP ( P<0.05) ; low serum t-PINP/β-CTX ratio after 1 year of treatment expression, and low 25 (OH) D levels showed a positive interaction in OP occurrence in a superphase multiplicative model ( P<0.05) . Conclusion:Serum t-PINP/β-CTX ratio and 25 (OH) D level are closely associated with the occurrence of OP after DTC in elderly women, and postoperative monitoring can help prevent and treat OP.

Correlation between serum SOST, DKK-1 levels and bone metabolism indexes in patients with osteoporosis after differentiated thyroid cancer surgery / 中华内分泌外科杂志

Objective:To investigate the correlation between serum recombinant sclerostin (SOST) and dickkopf-related protein 1 (DKK-1) levels and bone metabolism indexes in patients with osteoporosis after differentiated thyroid cancer surgery.Methods:A total of 110 patients diagnosed with osteoporosis after differentiated thyroid cancer surgery were recruited as the study group, and another 110 patients without osteoporosis diagnosed after differentiated thyroid cancer surgery were recruited as the control group. The general data, bone mineral density, serum SOST, DKK-1 levels and bone metabolism indicators N-terminal propeptide of type I procollagen (PINP), bone alkaline phosphatase (BALP), beta-isomerized C-telopeptide (β-CTX), 25-hydroxyvitamin D3 [25- (OH) D3] levels were compared between the two groups. The correlation between serum SOST, DKK-1 levels and bone metabolism indexes was analyzed, and the risk factors affecting the formation of osteoporosis were explored.Results:The T value of bone mineral density in the study group (-3.27±0.92) was significantly lower than that in the control group (-1.23±0.27, t=22.32, P<0.001). The serum SOST (15.84±1.34, t=32.53, P<0.001) and DKK-1 (5.96±1.40, t=4.82, P<0.001) levels in the study group were significantly higher than those in the control group (SOST: 10.24±1.21, DKK-1: 5.05±1.40). The serum PINP (40.95±9.84, t=7.59, P<0.001), BALP (23.14±5.26, t=5.06, P<0.001) and β-CTX (1.07±0.54, t=4.96, P<0.001) in the study group were significantly higher than those in the control group (31.48±8.64, 19.64±4.99, 0.78±0.29), and the 25- (OH) D3 level (13.68±4.49) was significantly lower than that of the control group (18.31±5.72, t=6.68, P<0.001). Serum SOST was positively correlated with PINP ( r=0.33, P=0.001), BALP ( r=0.23, P=0.016) and β-CTX ( r=0.19, P=0.046), but not with 25- (OH) D3 ( r=-0.09, P=0.349). Serum DKK-1 was positively correlated with PINP ( r=0.19, P=0.044), BALP ( r=0.26, P=0.007) and β-CTX ( r=0.21, P=0.028), but not with 25- (OH) D3 ( r=-0.16, P=0.088). Serum SOST and DKK-1 levels were independent risk factors for osteoporosis (all P<0.05) . Conclusion:Serum SOST and DKK-1 levels are independent risk factors for the formation of osteoporosis, which are significantly positively correlated with bone metabolism indexes PINP, BALP, and β-CTX in patients with osteoporosis after differentiated thyroid cancer surgery.

Review of advances in chemotherapy for thyroid cancer / 中华内分泌外科杂志

The incidence of thyroid cancer has continued to increase. Most thyroid cancer patients have good prognosis, but there are still some patients who will develop into the middle or late stage. The status of cytotoxic treatment in thyroid cancer treatment is controversial. Chemotherapy, as a classical malignant tumor treatment, has its unique significance for the special type and the special period of thyroid cancer. Chemotherapy can be an option for systemic treatment if no other treatment is available for patients of differentiated thyroid carcinoma refractory to radiodine in rapid progression and life-threatening period. For patients of anaplastic thyroid cancer in progression period, chemotherapy can be selected if there are no other treatments in clinical trials. And "Chemical therapy plus" treatment model might play an important role in thyroid treatment, because with the development of targeted drugs and immunotherapy, chemotherapy combined with other treatments can reduce the dosage of chemotherapy drugs to reduce the toxic side effect, and can improve other therapeutic effects.