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.

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.

Antineoplastic properties of polyphenols in TPC-1 human papillary thyroid carcinoma cell line: a systematic review

ABSTRACT Thyroid cancer usually responds to surgical and ablative therapy, but when it's refractory the alternative lies in tyrosine kinase inhibitors that, in addition to harmful side effects, acts only in a palliative way. The concern for other therapeutic possibilities brought evidence on flavonoids, hypothesizing a possible strategy. This review aimed to organize a compilation of in vitro studies using polyphenol substances in TPC-1 (human papillary thyroid carcinoma cell line) summarizing it's results and describing the metabolic pathways involved. Articles were selected on PubMed, Google Scholar, LILACS, BVS and SciELO, using keywords "thyroid cancer", "flavonoids" and "TPC-1", until June 2022. 185 studies were selected. After identification and exclusion of duplicates and exclusion criteria applied, 11 original articles were evaluated. Of these, the findings of flavonoids added to TPC-1 were: inhibition of cell growth and viability, promotion of cell cycle arrest and induction of apoptosis. Polyphenolic compounds have antineoplastic properties by different mechanisms as shown in vitro, but the concentrations needed are above usual dietary consumption and the findings are limited to experimental cellular studies. Despite that, these results should be useful to guide further analysis aiming to reveal the real safety and efficacy of polyphenols in this scenario.

Metastatic diffuse follicular variant papillary thyroid cancer without cervical lymph node metastasis presenting with symptoms related to hypopituitarism

ABSTRACT In this article, we present a case of diffuse follicular variant papillary thyroid carcinoma with pituitary metastasis, which is a rare cause of pituitary metastasis. The follicular variant of papillary thyroid carcinoma is an uncommon variant of papillary carcinoma. A 74-year-old male was presented with weakness, fatigue, and a decreased appetite. The patient was diagnosed with secondary adrenal and thyroid insufficiencies. Imaging revealed a pituitary mass with suprasellar extension, right cavernous sinus invasion, and optic chiasm compression. Thyroid ultrasonography revealed a nodule with a maximum size of 7.2cm in the right lobe. Cytological examination via fine-needle aspiration suggested papillary thyroid cancer. Total thyroidectomy with central and right lateral neck dissection confirmed the diagnosis of diffuse follicular variant of papillary thyroid carcinoma. Owing to visual field defects, the patient underwent transsphenoidal surgery. Histological and immunohistochemical evaluations confirmed pituitary metastasis from the papillary thyroid cancer. Radioactive iodine treatment and gamma knife radiotherapy of the pituitary gland were performed. The initiation of sorafenib treatment was deemed appropriate during the follow-up. A significant decrease in the thyroglobulin levels was observed after sorafenib treatment. Pituitary metastasis should be considered in patients diagnosed with hypopituitarism and pituitary lesions at initial evaluation. The presence of visual field defects may be an indication for neurosurgical intervention and guide both diagnosis and treatment. The management of papillary thyroid cancer and the role of treatment modalities in prognosis depend on the biological behavior of the tumor. Early diagnosis and multidisciplinary management are crucial for the treatment of these patients.

Precisión de la PAAF en el reporte histopatológico de cirugía de tiroides

Objetivo: evaluar la precisión de los distintos puntos de corte del score Bethesda de la BAAF, en comparación con el estudio histopatológico para el diagnóstico de patología tiroidea. Métodos: estudio cuantitativo, observacional, de tipo transversal, analítico para la evaluación de pruebas diagnósticas. Incluyó 293 pacientes con patología tiroidea sugestiva de cáncer, que acudieron a Servicio de Cirugía General del Hospital Obrero N° 2 de la Caja Nacional de Salud, durante el periodo de 2019-2022. Se realizó un muestreo no aleatorizado por conveniencia que incluía a todos los pacientes disponibles. Resultados: se afirma la correlación entre las dos variables estudiadas, es decir, entre el puntaje del score Bethesda y el reporte del estudio histopatológico, con un intervalo de confianza (IC) del 95%. Conclusiones: se demuestra que la BAAF tiene alta especificidad en el diagnóstico de cancer de tiroides con reporte Bethesda V y VI, por el contrario, reportes Bethesda menores II, III y IV, descartan el diagnóstico.

Objective: to evaluate the precision of the different cut-off points of the BAAF Bethesda score in comparison with the histopathological study for the diagnosis of thyroid pathology. Methods: quantitative, observational, cross-sectional, analytical study for the evaluation of diagnostic tests. It included 293 patients with thyroid disease suggestive of cancer, who attended the General Surgery Service of Hospital Obrero No. 2 of the National Health Fund, during the period 2019-2022. Non-randomized convenience sampling was performed that included all available patients. Results: the correlation between the two variables studied was confirmed, that is, between the Bethesda score and the histopathological study report, with a confidence interval (CI) of 95%. Conclusions: it is demonstrated that the BAAF has high specificity in the diagnosis of thyroid cancer with Bethesda reports V and VI, on the contrary, minor Bethesda reports II, III, and IV, rule out the diagnosis.

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.

Guidelines from the Brazilian society of surgical oncology regarding indications and technical aspects of neck dissection in papillary, follicular, and medullary thyroid cancers

ABSTRACT Objective: The purpose of these guidelines is to provide specific recommendations for the surgical treatment of neck metastases in patients with papillary, follicular, and medullary thyroid carcinomas. Materials and methods: Recommendations were developed based on research of scientific articles (preferentially meta-analyses) and guidelines issued by international medical specialty societies. The American College of Physicians' Guideline Grading System was used to determine the levels of evidence and grades of recommendations. The following questions were answered: A) Is elective neck dissection indicated in the treatment of papillary, follicular, and medullary thyroid carcinoma? B) When should central, lateral, and modified radical neck dissection be performed? C) Could molecular tests guide the extent of the neck dissection? Results/conclusion: Recommendation 1: Elective central neck dissection is not indicated in patients with cN0 well-differentiated thyroid carcinoma or in those with noninvasive T1 and T2 tumors but may be considered in T3-T4 tumors or in the presence of metastases in the lateral neck compartments. Recommendation 2: Elective central neck dissection is recommended in medullary thyroid carcinoma. Recommendation 3: Selective neck dissection of levels II-V should be indicated to treat neck metastases in papillary thyroid cancer, an approach that decreases the risk of recurrence and mortality. Recommendation 4: Compartmental neck dissection is indicated in the treatment of lymph node recurrence after elective or therapeutic neck dissection; "berry node picking" is not recommended. Recommendation 5: There are currently no recommendations regarding the use of molecular tests in guiding the extent of neck dissection in thyroid cancer.

Radioiodine (131I) treatment decision-making for low- and intermediate-risk differentiated thyroid cancer

ABSTRACT Objective: The purpose of this study was to investigate the effect and influencing factors of post-surgical radioactive iodine (RAI) therapy for patients with low- and intermediate-risk differentiated thyroid cancer (DTC). Subjects and methods: A retrospective analysis of 423 low- and intermediate-risk DTC patients admitted to the Department of Nuclear Medicine, Sichuan Provincial People's Hospital from January 2005 to December 2020 was performed. All patients were treated with surgery, had a postoperative pathological diagnosis, and were treated with RAI, including 89 males and 334 females. Recurrence risk stratification: 143 cases were low-risk, and 280 cases were intermediate-risk. Results: The excellent response (ER) rate for low- and intermediate-risk were 93.7% and 78.2%, respectively (P < 0.05). There were significant differences in age, cumulative dose of [131I], and pretreatment stimulated-Tg (pre-Tg) levels between the low- and intermediate-risk groups (P < 0.05). There were significant differences in the cumulative dose of 131I and pre-Tg levels between ER and the non-ER group (P < 0.05). The area under the curve (AUC) values were 0.799 in the low-risk group, and 0.747 in the intermediate-risk group for the ROC curve by ER status of pre-Tg. The ER rate with RAI treatment decreased with an increase in pre-Tg levels. Conclusion: Pre-Tg was an important factor for RAI treatment decision-making and prognostic evaluation and differed between low-risk and intermediate-risk DTC. Aggressive RAI therapy was recommended for low-risk DTC with pre-Tg ≥ 20.0 ng/mL and in intermediate-risk group with pre-Tg ≥ 10.0 ng/mL.

Increased tumor-associated mast cells facilitate thyroid cancer progression by inhibiting CD8+ T cell function through galectin-9

As an important component of solid tumors, mast cells show specific phenotypes in various tumor microenvironments. However, the precise mechanism of mast cell accumulation and the phenotypic features of thyroid cancer (TC) remain largely unknown. Here, we found that mast cells were obviously recruited to tumor tissue by TC-derived stem cell factor (SCF). With tumor progression, mast cell levels increased gradually. In addition, intratumoral mast cells expressed higher levels of the immunosuppressive molecule galectin-9, which effectively suppresses CD8+ T-cell antitumor immunity in vitro. Blocking galectin-9 on tumor-infiltrating mast cells reversed the immunosuppression of CD8+ T cells. In conclusion, our data elucidated novel protumorigenic and immunosuppressive roles of mast cells in TC. In addition, our results indicated that blocking mast cells may impede tumor progression and ameliorate the prognosis of TC patients.

Dawn of Advanced Thyroid Cancer Therapy: Targeted Therapy and Immunotherapy / 肿瘤防治研究

In recent years, the incidence of thyroid cancer has increased significantly. Most of the cases are differentiated thyroid cancer, which is characterized by a good prognosis. However, 15% of patients still have persistent or recurrent disease after initial treatment, and those with locally advanced or metastatic cancer are not cured with established treatments and at risk of death. The treatment of advanced thyroid cancer is still controversial at home and abroad, but it tends to targeted therapy and immunotherapy. With the in-depth understanding of the molecular pathogenesis of thyroid cancer, a variety of new targeted therapies have been approved for advanced thyroid cancer. The 2021 guidelines of the Chinese Society of Clinical Oncology (CSCO) and the 2022 guidelines of the European Society of Oncology (ESMO) regard targeted therapy as a level I recommendation for the treatment of advanced thyroid cancer. This article reviews the new progress in clinical treatment of advanced thyroid carcinoma.

Progress on Targeted Therapy of Radioiodine-refractory Differentiated Thyroid Cancer / 肿瘤防治研究

Targeted therapy has brought revolutionary breakthroughs for radioiodine-refractory differentiated thyroid cancer. New targeted drugs have prolonged the survival of patients with advanced differentiated thyroid cancer. Multiple tyrosine kinase inhibitors, represented by sorafenib and lenvatinib, have remarkably improved the progression-free survival of patients. Novel tyrosine kinase inhibitors targeting BRAF and RET mutation have also achieved remarkable curative effects, greatly enriching the treatment methods for thyroid cancer. This article reviews the latest research progress on targeted therapy in radioiodine-refractory differentiated thyroid cancer.

Progress and challenges in RET-targeted cancer therapy / 医学前沿

The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

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.