The auxiliary diagnostic value of combined detection of serum midkine and thyroid stimulating hormone for differentiated thyroid cancer / 中国医师进修杂志

Objective:To investigate the auxiliary diagnostic value of serum midkine (MK) and thyroid stimulating hormone (TSH) for differentiated thyroid cancer (DTC).Methods:Seventy-one postoperative DTC patients (DTC group) treated with 131I were selected, and 143 patients with benign thyroid lesions (benign thyroid disease group) treated with surgery in Center Hospital of Xiaogan from March 2019 to December 2020 at the same period were also selected. Clinical data such as liver and kidney function indexes, positive rate of anti thyroglobulin antibodies (TGAb) and positive rate of thyroid peroxidase antibody (TPOAb) were collected before treatment, and their fasting blood samples were collected before treatment. Fully automated electrochemiluminescence immunoassay was used to measure free thyroxine (FT 4), free triiodothyronine (FT 3), TSH levels in patients′ serum. The serum MK levels were measured by enzyme-linked immunosorbent assay (ELISA). Binary Logistic regression model was used to screen for independent risk factors for the development of DTC. A receiver operating characteristic curve (ROC) was drawn to evaluate the efficacy of MK, TSH and MK combined with TSH, in aiding the diagnosis of DTC and its staging. Results:Serum TSH and MK levels in DTC group were higher than those in benign thyroid disease group: (3.55 ± 0.61) mU/L vs. (2.97 ± 0.46) mU/L, (394.25 ± 63.36) ng/L vs. (311.45 ± 42.66) ng/L, and the differences were statistically significant ( P<0.05). Elevated serum TSH and MK levels were independent risk factors for DTC. When MK combined with TSH was used to diagnose DTC, the area under the curve (AUC), sensitivity and specificity were higher than those of MK and TSH alone (0.925 vs. 0.859 and 0.783, 83.10% vs. 78.87% and 73.24%, 89.51% vs. 85.31% and 79.02%), and the differences were statistically significant ( P<0.05). Serum TSH and MK levels in stage Ⅲ and Ⅳ patients in DTC group were higher than those in stage Ⅰ and Ⅱ patients: (3.79 ± 0.65) mU/L vs. (3.42 ± 0.56) mU/L, (427.88 ± 52.73) ng/L vs. (311.45 ± 42.66) ng/L, and the differences were statistically significant ( P<0.05). The AUC, sensitivity and specificity of MK combined with TSH in the diagnosis of different stages of DTC were higher than those of MK and TSH alone (0.822 vs. 0.657 and 0.666, 73.90% vs. 56.52% and 56.52%, 83.33% vs. 77.08% and 79.17%), and the differences were statistically significant ( P<0.05). Conclusions:Serum TSH and MK levels are independent risk factors for the occurrence of DTC in patients, and the combination of them has certain auxiliary diagnostic value for the identification and staging of DTC.

Small bowel perforation and death caused by anaplastic thyroid carcinoma metastasis in a patient with concomitant colonic and bilateral breast carcinoma

Undifferentiated or anaplastic thyroid carcinoma (ATC) is rare and one of the most aggressive human malignancies. The tumor is usually voluminous and fast-growing and mostly affects older women. The most common sites of distant metastases are the lungs, brain, and bones. Herein, we describe the case of a 66-year-old woman with a history of bilateral breast carcinoma and ATC, who presented with an acute abdomen and subsequently died. At autopsy, an isolated metastasis of ATC in the small intestine leading to bowel perforation was found. Moreover, there was adenocarcinoma in the descending colon. The review of extra-abdominal malignancies metastasizing to bowel and coincidence of breast and thyroid carcinoma is included.

El Rol de la Radioterapia en el Cáncer Diferenciado de Tiroides: Serie de Casos y Revisión de Literatura / The Role of Radiotherapy in the Different Cancer of Tiroides: Case Series and Literature Review

Introducción: El manejo inicial del cáncer diferenciado de tiroides (CDT) usualmente comprende la cirugía que puede acompañarse según el riesgo de recurrencia de la administración del yodo radioactivo (I-131); sin embargo, existe un pequeño grupo de pacientes que se catalogan como refractarios al I131, lo cual incide directamente en su pronóstico y expectativa de vida, siendo necesario evaluar opciones locales de tratamiento antes de avanzar a las terapias sistémicas y en estas condiciones la radioterapia (RTP) representa una opción local con fines de tratamiento primario o paliativo Métodos:Se realizó un estudio epidemiológico, descriptivo, retrospectivo, de centro único, que involucra a 49 pacientes con CDT e indicación de radioterapia. Resultados:En el 80% de los casos la edad fue mayor de 45 años, con predominio 74% en el sexo femenino, todos con diagnóstico de CDT sometidos a cirugía, 88%con variante no agresiva, 57% con un tamaño tumoral entre 1 a 4cm, 71% con extensión extratiroidea, 71% con metástasis ganglionares cervicales, 45% estadio TNM I y el 71% con alto riesgo de recurrencia. El 96% recibió I-131, con necesidad de reintervenciones quirúrgicas hasta por 5 o más ocasiones (8%). Recibieron RTP 57%con fines curativos y 43% paliativos. La técnica de radioterapia utilizada en el 69% de los pacientes fue IMRT/VMAT, y la dosis más frecuentemente empleada fue ≥ 60Gy en región cervical (61%). De los 49 pacientes, el 90% tiene respuesta estructural incompleta y 12% falleció por CDT. Conclusiones:La radioterapia debe considerarse en enfermedad avanzada localmente con extensión extratiroidea, enfermedad residual macroscópica y tumor irresecable o recurrente que falla a la terapia convencional del CDT. Palabras clave:Neoplasias de la Tiroides, Carcinoma Anaplásico de Tiroides, Tiroidectomía, Recurrencia Local de Neoplasia, recurrencia, /radioterapia

Introduction:The initial management of differentiated thyroid cancer (DTC) usually includes surgery that can be accompanied according to the risk of recurrence of the administration of radioactive iodine (I-131). However, there is a small group of patients who are classified as refractory to I-131, which directly affects their prognosis and life expectancy, making it necessary to evaluate local treatment options before advancing to systemic therapies and, in these conditions, radiotherapy (RTP) represents a local option for primary or palliative treatment purposes. Methods:An epidemiological, descriptive, retrospective, single-center study was carried out, involving 49 patients with DTC and indication for radiotherapy. Results:In 80% of the cases the age was over 45 years, with a 74% predominance in the female sex, all with a diagnosis of DTC undergoing surgery, 88% with a non-aggressive variant, 57% with a tumor size between 1 at 4cm, 71% with extrathyroid extension, 71% with cervical lymph node metastases, 45% TNM stage I, and 71% with a high risk of recurrence. 96% received I-131, requiring reoperations for up to 5 or more occasions (8%). 57% received RTP for curative purposes and 43% palliative. The radiotherapy techniqueused in 69% of the patients was IMRT / VMAT, and the most frequently used dose was ≥60Gy in the cervical region (61%). Of the 49 patients, 90% had an incomplete structural response and 12% died from DTC. Conclusions:Radiation therapy should be consideredin locally advanced disease with extrathyroid extension, macroscopic residual disease and unresectable or recurrent tumor that fails conventional therapy for DTC. Keywords:Thyroid Neoplasms; Thyroid Carcinoma,Anaplastic;Thyroidectomy;Neoplasm Recurrence, Local;/radiotherapy

Recent Improvements in Genomic and Transcriptomic Understanding of Anaplastic and Poorly Differentiated Thyroid Cancers

Anaplastic thyroid cancer (ATC) is a lethal human cancer with a 5-year survival rate of less than 10%. Recently, its genomic and transcriptomic characteristics have been extensively elucidated over 5 years owing to advance in high throughput sequencing. These efforts have extended molecular understandings into the progression mechanisms and therapeutic vulnerabilities of aggressive thyroid cancers. In this review, we provide an overview of genomic and transcriptomic alterations in ATC and poorly-differentiated thyroid cancer, which are distinguished from differentiated thyroid cancers. Clinically relevant genomic alterations and deregulated signaling pathways will be able to shed light on more effective prevention and stratified therapeutic interventions for affected patients.

Combined Effects of Baicalein and Docetaxel on Apoptosis in 8505c Anaplastic Thyroid Cancer Cells via Downregulation of the ERK and Akt/mTOR Pathways

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effects and drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with many advantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In this study, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells. METHODS: The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforming growth factor β [TGF-β], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis. RESULTS: The combination of baicalein (50 or 100 µM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosis compared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF-β1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylation of ERK and Akt. CONCLUSION: The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cells through downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505c cells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC.

Hipercalcemia paraneoplásica de carcinoma anaplásico da tireoide / Paraneoplastic hypercalcemia of anaplastic thyroid carcinoma: case report

A hipercalcemia deve ser considerada no diagnóstico diferencial de alterações neuropsiquiátricas agudas. Em 90% dos casos, a etiologia corresponde a hiperparatireoidismo primário ou neoplasias. Valores séricos superiores a 14mg/dL e sintomáticos são frequentemente tradutores de causa maligna. O carcinoma anaplásico da tireoide consiste em um tumor indiferenciado, com progressão rápida e prognóstico reservado, que evolui, em alguns casos, a partir de lesões tireóideas preexistentes, benignas ou malignas (desdiferenciação). Embora a apresentação clínica mais frequente destes tumores consista no desenvolvimento de massa cervical, eles podem ser diagnosticados no esclarecimento etiológico de metástases ou síndromes paraneoplásicos. A hipercalcemia, associada à neoplasia, pode ocorrer em contexto de metástases ósseas, com libertação de citocinas, ou por mecanismo humoral, mediada pela proteína relacionada ao hormônio hormônio paratireóideo (PTHrP). Os autores descrevem o caso de uma mulher de 85 anos, com antecedentes de bócio multinodular benigno, internada para esclarecimento etiológico de hipercalcemia grave, com manifestações neuropsiquiátricas, diagnosticando-se, após avaliação, carcinoma anaplásico da tireoide. O caso foi abordado em reunião multidisciplinar, optando-se por limitação terapêutica a cuidados paliativos. A doente faleceu 3 meses após o diagnóstico.(AU)

Hypercalcaemia should be considered in the differential diagnosis of acute neuropsychiatric disorders. In 90% of the cases, the etiology corresponds to primary hyperparathyroidism or neoplasms. Serum values above 14mg/dL and symptomatic are often indicative of a malignant cause. The anaplastic thyroid carcinoma consists of an undifferentiated tumor, with rapid progression and poor prognosis, which in some cases progresses from pre-existing benign or malignant thyroid diseases (dedifferentiation). Although the most frequent clinical presentation of these tumors consists of the development of a cervical mass, they can be diagnosed in the etiological clarification of metastases or paraneoplastic syndromes. Neoplasm-associated hypercalcaemia may occur in the context of bone metastasis, with release of cytokines, or through a humoral mechanism, mediated by the parathyroid hormone (PTHrP)-related protein. The authors describe the case of an 85-year-old woman with a history of multinodular benign goiter, hospitalized for etiological elucidation of severe hypercalcaemia with neuropsychiatric manifestations, with a final diagnosis of anaplastic thyroid carcinoma, after the diagnostic evaluation. The case was approached in a multidisciplinary meeting, and the therapeutic limitation to palliative care was chosen. The patient died 3 months after the diagnosis.(AU)

Macrophage Densities Correlated with CXC Chemokine Receptor 4 Expression and Related with Poor Survival in Anaplastic Thyroid Cancer

BACKGROUND: Tumor associated macrophages (TAMs) and CXC chemokine receptor 4 (CXCR4) have emerged as potential biomarkers in various human cancers. The aims of this study were to investigate the clinical characteristics of anaplastic thyroid cancer (ATC) patients according to the TAM numbers in the tumor tissue, and to evaluate the associations between CXCR4 expressions and macrophage densities in ATC tumor microenvironment. METHODS: Total 14 ATC samples from thyroid tissue microarray were used. Immunohistochemical staining was performed using anti-CD163 and anti-CXCR4 antibodies. According to the immunoreactivity of CD163, all subjects were divided into two groups: low-CD163 (n=8) and high-CD163 (n=6) groups. RESULTS: The mean diagnostic age was 65±7 years and the median tumor size was 4.3 cm, ranging 2.5 to 15 cm. Clinicopathological characteristics were not significantly different between low-CD163 and high-CD163 groups, while age of diagnosis was younger in high-CD163 group than that of low-CD163 group with marginal significance (56.9±5.5 years vs. 67.5±6.8 years, P=0.09). However, overall survival was significantly reduced in high-CD163 group (5.5 months [range, 1 to 10]) compared with low-CD163 groups (8.8 months [range, 6 to 121); log-rank test, P=0.0443). Moreover, high-CD163 group showed strong CXCR4 expressions in both cancer and stromal compartments, while low-CD163 group showed relatively weak, stromal-dominant CXCR4 expressions. Additionally, CD163 and CXCR4 expressions showed a strong positive correlation (γ²=0.432, P=0.013). CONCLUSION: Increased number of TAMs showed poor overall survival in ATC, suggesting TAMs are potentially a prognostic biomarker for ATC. CXCR4 expression was significantly correlated with CD163-positive TAM densities, which suggest the possible role of CXCR4 in TAM recruitments.