Guía de práctica clínica para el tratamiento y seguimiento de personas con cáncer diferenciado de tiroides. Parte I: Vigilancia activa

Introducción: El cáncer de tiroides es una enfermedad frecuente en el mundo, con mayor prevalencia del tipo diferenciado. El diagnóstico temprano y manejo pertinente, individualizado y adaptable puede mejorar su pronóstico. Objetivo: Generar recomendaciones basadas en evidencia sobre el tratamiento y seguimiento de personas adultas con cáncer diferenciado de tiroides (CDT). Metodología: Guía de práctica clínica (GPC) a partir de revisión sistemática de literatura (RSL) y consenso de expertos clínicos. El grupo desarrollador definió el alcance y cuatro preguntas que se resolvieron a través de revisión de evidencia de GPC existentes, RSL, estudios primarios publicadas en español o inglés en diferentes fuentes de información desde 2013. Las preguntas de investigación fueron: 1. ¿Cuáles son las indicaciones de la vigilancia activa?, ¿cómo realizarla?, ¿cuándo y con que periodicidad realizarla? 2. ¿Cuál es el tratamiento y su indicación en pacientes con nódulos tiroideos sospechosos de cáncer? 3. ¿Cómo y cuándo realizar seguimiento de pacientes con CDT de acuerdo con el riesgo dinámico? 4. ¿Cuál es el manejo actual de los pacientes iodo refractarios? Se propusieron recomendaciones basadas en la evidencia, y analizadas y discutidas por el colectivo experto en sesiones asincrónicas. Se evalúo la calidad de la evidencia y las recomendaciones fueron gradadas en fuerte o condicional y a favor o en contra a partir del análisis de la calidad de la evidencia, contexto de implementación (disponibilidad e implementación) y la experticia clínica. En el presente documento se desarrollada la primera pregunta, referente a vigilancia activa. Resultados: 86 recomendaciones fueron propuestas y acordadas por el grupo desarrollador, categorizadas en tratamiento y seguimiento para resolver las preguntas planteadas. 10 de las recomendaciones corresponden a vigilancia activa y se incluyen en el presente documento. Recomendaciones claves incluyen, brindar información completa y oportuna a pacientes, conformación de equipos multidisciplinarios, análisis individualizado del paciente para la decisión de tratamiento, estadificación rutinaria de riesgo dinámico para evaluar la respuesta al tratamiento y ajustarlo, minimización de procedimientos fútiles o que aportan poco a la supervivencia y calidad de vida de los pacientes. Conclusión: Se presentan recomendaciones que esperan incidir en la estandarización de la práctica clínica cotidiana de pacientes con CDT y mejores resultados en salud.

Introduction: Thyroid cancer is a common disease in the world, with a higher prevalence of the differentiated type. Early diagnosis individualized and adaptive management can improve prognosis. Objective: Generate evidence-based recommendations on the treatment and follow-up of adults with differentiated thyroid carcinoma (DTC). Methodology: Clinical practice guideline (CPG) based on systematic literature review (RSL) and consensus of clinical experts. The development group defined the range and four questions that were resolved through a review of evidence from existing CPGs, RSLs, primary studies published in Spanish or English in various sources of information since 2013. The research questions were: 1. What are the indications for active surveillance? How to carry it out? When and how often to carry it out? 2. What is the treatment and its indication in patients with thyroid nodules suspicious for cancer? 3. How and when to follow up patients with CDT according to dynamic risk? 4. What is the current management of iodine refractory patients? Evidence-based recommendations analyzed and discussed by the expert group in asynchronous sessions were proposed. The quality of the evidence was evaluated, and the recommendations were graded as strong or conditional and in favor or against based on the analysis of the quality of the evidence, implementation context (availability and implementation) and clinical expertise. In this document, is developed the first question, referring to active surveillance. Results: 86 recommendations were proposed and agreed upon by the development group, categorized into treatment and follow-up to solve the questions raised. 10 of the recommendations correspond to active surveillance and are included in this document. Key recommendations include providing complete and timely information to patients, develop of multidisciplinary teams, individualized patient analysis for treatment decisions, routine dynamic risk staging to evaluate response to treatment and adjust it, minimization of futile procedures or that contribute little to the survival and quality of life of patients. Conclusion: Recommendations are presented that longs to influence the standardization of the daily clinical practice of patients with DTC and better health outcomes.

Surgical safety and effectiveness of bilateral axillo-breast approach robotic thyroidectomy: a systematic review and meta-analysis

Abstract Objectives To assess the safety and effectiveness of bilateral axillo-breast approach robotic thyroidectomy in thyroid tumor. Methods Bilateral axillo-breast approach robotic thyroidectomy and other approaches (open thyroidectomy, transoral robotic thyroidectomy, and bilateral axillo-breast approach endoscopic thyroidectomy) were compared in studies from 6 databases. Results Twenty-two studies (8830 individuals) were included. Bilateral axillo-breast approach robotic thyroidectomy had longer operation time, greater cosmetic satisfaction, and reduced transient hypoparathyroidism than conventional open thyroidectomy. Compared to bilateral axillo-breast approach endoscopic thyroidectomy, bilateral axillo-breast approach robotic thyroidectomy had greater amount of drainage, lower chances of transient vocal cord palsy and permanent hypothyroidism, and better surgical completeness (postopertive thyroblobulin level and lymph node removal). Bilateral axillo-breast approach robotic thyroidectomy induced greater postoperative drainage and greater patient dissatisfaction than transoral robotic thyroidectomy. Conclusion Bilateral axillo-breast approach robotic thyroidectomy is inferior to transoral robotic thyroidectomy in drainage and cosmetic satisfaction but superior to bilateral axillo-breast approach endoscopic thyroidectomy in surgical performance. Its operation time is longer, but its cosmetic satisfaction is higher than open thyroidectomy.

Bilateral choroidal metastasis of follicular thyroid carcinoma 7 years after total thyroidectomy: a case report

ABSTRACT Follicular thyroid cancers account for 15%-20% of all thyroid tumors. Choroidal metastases secondary to follicular thyroid cancer rarely occur. Herein, we report the case of an 85-year-old woman who presented choroidal metastasis from a follicular thyroid carcinoma in the right eye 7 years after total thyroidectomy and underwent enucleation. To confirm the diagnosis and primary tumor site, histopathological, and immunohistochemical examinations were performed. One year later, she presented metastasis in the contralateral eye. Few similar cases have been described in the literature.

Benign cervical schwannoma with tracheal invasion

ABSTRACT Schwannomas commonly develop in the cervical region, 25% - 45% of cases are diagnosed in this anatomical region. Tracheal neurogenic tumors are exceedingly rare and can be misdiagnosed as invasive thyroid carcinomas or other infiltrating malignancies when present at the level of the thyroid gland. Here, we present a case of synchronous benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma in a patient who was initially hospitalized for COVID-19. The patient presented with dyspnea that was later found to be caused by tracheal extension of a cervical tumor. Surgical excision was performed, and the surgical team proceeded with segmental tracheal resection, removal of the cervical mass, and total thyroidectomy. The specimen was sent for pathological analysis, which revealed synchronous findings of a benign cervical schwannoma with tracheal invasion and papillary thyroid carcinoma. The literature on this subject, together with the present case report, suggests that neurogenic tumors should be included in the differential diagnosis of obstructing tracheal cervical masses. Surgical excision is the first-line of treatment for benign cervical schwannomas.

Clinical manifestations of I-131 induced salivary gland dysfunction in patients with thyroid carcinoma

Aim: To carry out a retrospective analysis of the frequency and severity of clinical signs of radioiodine (131I)-induced damage to the salivary glands in the early and long-term post-radiation periods, and identify risk factors for their occurrence in patients with differentiated thyroid carcinomas. Methods: A total of 330 patients underwent thyroidectomy with dissection of lymphatic nodes. One month after surgery, all the patients received radioiodine therapy. The dose and number of courses varied depending on the stage and morphological type of the tumor. In the late post-radiation period, the patients were surveyed with the use of a standard questionnaire, which allowed retrospective assessment of the nature and severity of symptoms of radiationinduced damage, as well as the time of their onset/subsidence. Results: Radiation-induced sialoadenitis of the salivary glands was observed in 51.2% of patients treated with 131I. The main symptoms included pain and discomfort in the salivary glands (51.2% of patients), swelling (48.8%), transient or permanent dry mouth (38%), and distortion of taste (38%). There were statistically significant correlations between the presence and severity of the main clinical symptoms of salivary gland irradiation. A significant relationship (r = 0.91, p < 0.001) was found between swelling of the salivary glands and the feeling of pain or discomfort, which was indicative of inflammation and retention of saliva. Conclusion: The main factors influencing the formation of chronic radiation-induced sialoadenitis and the severity of the inflammatory process included the tumor stage, the total dose of radiopharmaceuticals, and the duration following radioiodine therapy

Prevalencia de Metástasis torácicas en pacientes con cáncer de Tiroides en el Instituto Nacional de Cancerología entre 2016 y 2019, en Bogotá, Colombia / Prevalence of Thoracic Metastases in Patients with Thyroid Cancer at the National Cancer Institute between 2016 and 2019 in Bogotá, Colombia

Introducción: El cáncer de tiroides es la neoplasia endocrina más prevalente y el tercer tumor más frecuente en las mujeres colombianas. Tiene buen pronóstico en ausencia de metástasis. Los pulmones son el tejido más comprometido por metástasis en pacientes con cáncer de tiroides. El objetivo del trabajo fue describir la prevalencia de las metástasis torácicas en pacientes con cáncer de tiroides en un centro de referencia en cáncer de la ciudad de Bogotá entre 2016 y 2019. Material y métodos: El estudio fue de corte transversal con muestreo no probabilístico de casos consecutivos en pacientes mayores de 18 años con cáncer de tiroides que asistieron a consulta externa de del Instituto Nacional de Cancerología entre 2016 y 2019. Resultados: Se incluyeron 241 pacientes; 53 presentaron metástasis torácicas. Dentro de los pacientes con metástasis el promedio de edad fue de 59,6 años (DE ± 12,7), 77,3% fueron mujeres, y el 90,5% presentó carcinoma papilar. La prevalencia de metástasis torácicas fue del 21,9%. Las comorbilidades más frecuentes fueron hipertensión arterial (32,08%). El síntoma más frecuente fue la disnea en un 15%. El 34% presentaron tiroglobulina mayor de 38 ng/mL y un 22% tenían anticuerpos antitiroglobulina detectables. Las variables asociadas a metástasis torácicas fueron la edad (p = 0,002), el peso (p = 0,019), adenopatías cervicales (p = 0,007), presencia de disnea (p = 0,004) y tiroglobulina mayor de 38 ng/mL (p < 0,001). La presencia de adenopatías cervicales se encontró en el 86% de los pacientes con metástasis, lo que sugiere que se trata de un marcador de riesgo de metástasis. Conclusiones: El presente estudio permite establecer datos locales, cuyos resultados promueven futuros estudios prospectivos que identifiquen variables asociadas y factores pronósticos en pacientes con cáncer de tiroides.

Introduction: Thyroid cancer is the most prevalent endocrine neoplasm and the third most common tumor in Colombian women. It has a good prognosis in the absence of metastasis. The lungs are the most affected tissue by metastasis in patients with thyroid cancer. The objective of this work was to describe the prevalence of thoracic metastases in patients with thyroid cancer in a cancer reference hospital from Bogotá, between 2016 and 2019. Materials and methods: The study was cross-sectional, with non-probabilistic sampling of consecutive cases in patients older than 18 with thyroid cancer who were attended at the National Cancer Institute between 2016 and 2019. Results: 241 patients were included in the study; 53 had thoracic metastases. The mean age of patients with metastasis was 59.6 years (SD ± 12.7); 77.3% were female and 90.5% showed papillary carcinoma. The prevalence of thoracic metastases was 21.9%. The most common comorbidity was arterial hypertension (32.08%). The most common symptom was dyspnea, with 15%. 34% of patients had thyroglobulin of more than 38 ng/ml and 22% had detectable anti-thyroglobulin antibodies. Variables associated with thoracic metastases were age (p = 0.002), weight (p = 0.019), cervical adenopathies (p = 0.007), presence of dyspnea (p = 0.004), and thyroglobulin values greater than 38 ng/ml (p < 0.001). Cervical adenopathies were found in 86% of patients with metastasis, suggesting the fact that they are a risk marker for metastasis. Conclusions: This study allows us to establish local data, whose results promote future prospective studies that identify associated variables and prognostic factors in patients with thyroid cancer.

Cáncer de tiroides en pediatría: a propósito de una entidad poco frecuente

El cáncer de tiroides es una entidad infrecuente en población pediátrica, tiene un conjunto único de características clínicas, patológicas y moleculares en niños. La clínica típica es un nódulo tiroideo de meses de evolución asintomático, como en el caso descrito. En comparación con los adultos, los niños presentan con mayor frecuencia una enfermedad agresiva en etapa avanzada. La conducta de manejo y tratamiento es la cirugía de tiroides radical y el vaciamiento ganglionar amplio, luego yodoterapía y suplencia tiroidea. La supervivencia es excelente, a los 10 años es mayor a 98% sin embargo, se deben recordar las complicaciones relacionadas con el tratamiento de por vida las cuales no son infrecuente.

Thyroid cancer is a rare condition in the pediatric population, it has a unique set of clinical, pathological and molecular characteristics in children. The typical presentation is an asymptomatic thyroid nodule of months of evolution, as in the described case. Compared with adults, children more often present with late-stage aggressive disease. The management and treatment approach is radical thyroid surgery and extensive lymph node dissection, then iodotherapy and thyroid replacement. Survival is excellent, at 10 years it is greater than 98%, however, complications related to lifelong treatment, which are not uncommon, should be kept in mind.

Administración subcutánea de levotiroxina en hipotiroidismo refractario / Subcutaneous administration of levothyroxine in refrac tory hypothyroidism

Resumen El hipotiroidismo generalmente se puede tratar de manera efectiva con levotiroxina (LT-4) oral. Sin em bargo, el hipotiroidismo refractario al tratamiento con LT-4 es una condición clínica frecuente. Entre las causas se encuentra la falta de adherencia, interacciones con alimentos u otros medicamentos y enfermedades gas trointestinales, como enfermedad inflamatoria intestinal y síndromes de intestino corto. El aumento de la dosis oral de LT-4 no siempre es eficaz en estos escenarios. Por lo tanto, pueden ser necesarias otras vías de administración. En este reporte, evaluamos modalidades alternativas de tratamiento para el hipotiroidismo re fractario y presentamos dos pacientes con malabsorción intestinal tratadas con éxito mediante la administración subcutánea de LT-4.

Abstract Hypothyroidism can usually be treated effectively with oral levothyroxine (LT-4) supplementation. However, hypothyroidism refractory to treatment with LT-4 is a common clinical condition. Causes include poor com pliance, interactions with food or other medications, and gastrointestinal diseases, such as inflammatory bowel disease and short bowel syndromes. Increasing the oral dose of LT-4 is not always effective in these scenarios. Therefore, other routes of administration may be neces sary. In this report, we evaluate alternative treatment modalities for refractory hypothyroidism and present two patients with intestinal malabsorption successfully treated by subcutaneous administration of LT-4.

Dependence of radioactive iodine-131 capture by the lacrimal ducts on the tear production level

Purpose: Secondary acquired lacrimal duct obstruction (SALDO) is one of the complications of radioiodine therapy. SALDO is formed a few months after therapy if there is a sufficient uptake of radioactive iodine by the nasolacrimal duct. To date, risk factors leading to SALDO are unclear. The objective was to determine the correlation between the tear production level and radioactive iodine?131 uptake in the lacrimal ducts.Methods: Basal and reflex tear production was studied in 64 eyes prior to the therapy with radioactive iodine?131 after drug?induced hypothyroidism. The condition of the ocular surface was assessed using the Ocular Surface Disease Index (OSDI) questionnaire. Seventy?two hours after the radioactive iodine therapy, scintigraphy was performed, which determined the presence or absence of iodine?131 in the lacrimal ducts. T?statistics and the Mann–Whitney criterion were used to identify the differences between the groups. The differences were considered significant at P ? 0.05. The current tear production level in patients receiving radioiodine therapy was determined using a mathematical model. Results: A statistically significant difference between the basal (p = 0.044) and reflex (p = 0.015) tear production levels was found in cases with and without iodine?131 uptake by the lacrimal ducts. The probable current tear production level corresponds to the sum of basal and 10–20% of reflex tear production. The uptake of iodine?131 was found regardless of the OSDI results.Conclusion: The probability of iodine?131 uptake by the lacrimal ducts rises as the tear production level increases.

Establishment of random survival forest model of the prognosis of anaplastic thyroid cancer and its predictive efficacy analysis / 肿瘤研究与临床

Objective:To investigate the factors influencing the prognosis of anaplastic thyroid cancer (ATC) and to evaluate the application value of established random survival forest (RSF) model in the prognosis prediction of ATC.Methods:A total of 707 ATC patients diagnosed by histopathology in the Surveillance, Epidemiology and End Results (SEER) database of the National Cancer Institute from 2004 to 2015 were selected and randomly divided into the training set (495 cases) and the validation set (212 cases). Univariate Cox regression risk model was used to analyze the related factors affecting overall survival (OS) of patients in the training set. The multivariate Cox proportional risk model based on the minimum Akaike information criterion (AIC) was used to analyze the above variables and then the variables were screened out. The traditional Cox model for predicting OS was constructed based on the screened variables. The RSF algorithm was used to analyze the variables with P < 0.05 in the univariate Cox regression analysis, and 5 important features were selected. Multivariate Cox proportional risk model was selected based on the minimum AIC. Then the RSF-Cox model for predicting OS was constructed by using screened variables. The time-dependent receiver operating characteristic (tROC) curve and the area under the curve (AUC), calibration curve, decision curve and integrated Brier score (IBS) in the training set and the validation set were used to evaluate the prediction performance of the models. Results:Univariate Cox regression analysis showed that age, chemotherapy, lymph node metastasis, radiotherapy, surgical method, tumor infiltration degree, tumor number, tumor diameter and diagnosis time were factors affecting the prognosis of ATC (all P < 0.05). Multivariate Cox regression analysis based on minimal AIC (4 855.8) showed that younger age (61-70 years vs. > 80 years: HR = 0.732, 95% CI 0.56-0.957, P = 0.023; ≤ 50 years vs. > 80 years: HR = 0.561, 95% CI 0.362-0.87, P = 0.010), receiving chemotherapy (receiving or not: HR = 0.623, 95% CI 0.502-0.773, P < 0.001), receiving radiotherapy (receiving or not: HR = 0.695, 95% CI 0.559-0.866, P = 0.001), receiving surgery (lobectomy, no surgery or unknown: HR = 0.712, 95% CI 0.541-0.939, P = 0.016; total resection or subtotal resection vs. no surgery or unknown: HR = 0.535, 95% CI 0.436-0.701, P < 0.001), and tumor diameter (≤ 2 cm vs. > 6 cm: HR = 0.495, 95% CI 0.262-0.938, P = 0.031; > 2 cm and ≤ 4 cm vs. > 6 cm: HR = 0.714, 95% CI 0.520-0.980, P = 0.037; > 4 cm and ≤ 6 cm vs. > 6 cm: HR = 0.699, 95 % CI 0.545-0.897, P = 0.005) were independent protective factors for OS of ATC patients. Lymph node metastasis (N 1 unknown vs. N 0: HR = 1.664, 95% CI 1.158-2.390, P = 0.006; N 1b: HR = 1.312, 95% CI 1.029-1.673, P = 0.028), more aggressive tumor infiltration degree (group 3 vs. group 1: HR = 1.492, 95% CI 1.062-2.096, P = 0.021; group 4 vs. group 1: HR = 1.636, 95% CI 1.194 - 2.241, P = 0.002) were independent risk factors for OS of ATC patients. Although diagnosis time was not statistically significant (2010-2015 vs.2004-2009: HR = 1.166, 95% CI 0.962-1.413, P = 0.118), the inclusion of it could improve the efficacy of the traditional Cox model. RFS algorithm was used to select out 5 important variables: surgical method, tumor diameter, age group, chemotherapy, and tumor number. Multivariate Cox regression analysis based on minimum AIC (4 884.6) showed that chemotherapy (receiving or not: HR = 0.574, 95% CI 0.476-0.693, P < 0.001), surgical method (lobectomy, no surgery or unknown: HR = 0.730, 95% CI 0.567-0.940, P = 0.015; total resection or subtotal resection vs. no surgery or unknown: HR = 0.527, 95% CI 0.423-0.658, P < 0.001), tumor diameter (≤ 2 cm vs. > 6 cm: HR = 0.428, 95% CI 0.231-0.793, P = 0.007; > 2 cm and ≤ 4 cm vs. > 6 cm: HR = 0.701, 95% CI 0.513-0.958, P = 0.026; > 4 cm and ≤ 6 cm vs. > 6 cm: HR = 0.681, 95% CI 0.536-0.866, P = 0.002) were independent factors for OS of ATC patients. RSF-Cox model was constructed based on 3 variables. The tAUC curve analysis showed that RSF-Cox model for predicting the 6-month, 12-month, and 18-month OS rates were 93.56, 92.62, and 90.80, respectively in the training set, and 93.05, 92.47, and 90.20, respectively in the validation set; in the traditional Cox model, the corresponding OS rates were 89.00, 87.76, 85.24, respectively in the training set, and 86.22, 83.68, 82.86, respectively in the validation set. When predicting OS rate at 6-month, 12-month and 18-month, the calibration curve of RSF-Cox model was closer to 45° compared with that of traditional Cox model, and the clinical net benefit of decision curve in RSF-Cox model was higher than that in traditional Cox model. The IBS of RSF-Cox model (0.089) was lower than that of traditional Cox model (0.111). Conclusions:The RSF model based on chemotherapy, surgical method and tumor diameter can effectively predict the OS of ATC patients.

Expressions of eukaryotic initiation factor-4B and eukaryotic initiation factor-5A in papillary thyroid carcinoma and their effects on cell proliferation in vitro / 肿瘤研究与临床

Objective:To investigate the expressions of eukaryotic initiation factor-4B (eIF4B) and eukaryotic initiation factor-5A (eIF5A) in papillary thyroid carcinoma tissues, and to analyze their regulatory effects on cell proliferation in vitro.Methods:The clinical data of 61 patients diagnosed with papillary thyroid carcinoma who received surgical resection at Yuncheng Central Hospital from January 2020 to October 2021 were retrospectively analyzed. The postoperative tumor tissues and paracancerous normal thyroid tissues (>1 cm from the margin of the mass) were retained. Immunohistochemistry was used to detect the expressions of eIF4B, eIF5A and proliferating cell nuclear antigen (PCNA) in different tissues. The correlation of eIF4B, eIF5A expressions with the clinicopathological characteristics of patients, and the relationship between eIF4B, eIF5A and PCNA were analyzed. The thyroid cancer cell line SW1736 and normal thyroid cell line HT-ori3 were selected. The expressions of eIF4B mRNA and eIF5A mRNA were detected by using real-ime quantitative polymerase chain reaction (qRT-PCR). After the small interfering RNA (siRNA) of siRNA-eIF4B and siRNA-eIF5A were synthesized, the interfering plasmids were constructed, and SW1736 cells were transfected, siRNA-eIF4B group and siRNA-eIF5A group were obtained; the empty plasmid transfection group and the blank control group without transfection intervention were established. The cell proliferation activity was detected by using CCK-8 assay, and the expression of PCNA mRNA was detected by using qRT-PCR.Results:The positive rates of eIF4B and eIF5A in papillary thyroid cancer tissues were higher than those in paracancerous normal thyroid tissues [65.57% (40/61) vs. 29.51% (18/61), 57.38% (35/61) vs. 9.84% (6/61), P < 0.001]. The positive rates of eIF4B and eIF5A were statistically different in patients with different tumor diameter [>3 cm vs. ≤3 cm: 88.89% (16/18) vs. 55.81% (24/43),77.78% (14/18) vs. 48.84% (21/43), all P < 0.05], lymph node metastasis [with vs. without: 85.00% (17/20) vs. 56.10% (23/41), 80.00% (16/20) vs. 46.34% (19/41), all P < 0.05] and the number of different nodes [multiple vs. single: 86.67% (13/15) vs. 58.70% (27/46), 86.67% (13/15) vs. 47.83% (22/46), all P < 0.05]; there were no statistically significant differences in the positive rates of eIF4B and eIF5A among patients with different age and gender (all P > 0.05). Positive correlation was found between eIF4B score and the positive cell proportion of PCNA ( r = 0.66, P = 0.0324), eIF5A score and the positive cell proportion of PCNA ( r = 0.62, P = 0.024), eIF4B score and eIF5A score ( r = 0.63, P = 0.021). The expression levels of eIF4B mRNA and eIF5A mRNA in thyroid cancer cell line SW1736 cell was higher than that of HT-ori3 cell in normal thyroid (all P < 0.05). The cell proliferation activity of SW1736 and PCNA mRNA expression level in siRNA-eIF4B group and siRNA-eIF5A group were lower than those in the empty vector transfected group and the blank control group (all P < 0.05). Conclusions:eIF4B and eIF5A are expressed elevated in papillary thyroid carcinoma, and both are involved in tumor development and progression. The role of eIF4B and eIF5A may be related to promoting the proliferation of tumor cells.

Clinical analysis of gasless transoral endoscopic thyroidectomy via oral vestibular approach for papillary thyroid carcinoma / 中华普通外科杂志

Objective:To study the safety and feasibility of gasless transoral endoscopic thyroidectomy though vestibular approach using self-retaining retractor for papillary thyroid carcinoma.Methods:The clinical data of 39 papillary thyroid carcinoma patients undergoing gasless transoral endoscopic thyroidectomy were collected at Department of Head and Neck Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from Nov 2020 to Jun 2021.Results:All cases successfully underwent laparoscopic surgery without conversion to open surgery. The mean duration of operation was (142±35) min, and the postoperative mean hospital stay was (4.1±0.8) days. The mean maximum diameter of the tumor was (8.5±4.5) mm, and the mean number of lymph node harvest of by central compartment dissection was 7.7±5.9. Postoperative complications were transient hypoparathyroidism in 2 cases but recovered in 1 month. Scalp hydrop in 1 patient,fading subsequently. Transient sensory change around the lower lip in 3 cases, which recovered in 6 months. No patient suffered from recurrent laryngeal nerve palsy or hematoma, no permanent hypoparathyroidism occurred, nor of the postoperative bleeding .Conclusion:The gasless transoral endoscopic thyroidectomy viaoral vestibular approach is a feasible approach in selected papillary thyroid carcinoma patients.

To analyze the clinical characteristics of elderly patients with papillary thyroid carcinoma / 中华老年医学杂志

Objective:To analyze the clinical characteristics of elderly patients with papillary thyroid cancer(PTC)by age grouping.Methods:The patients were divided into three groups according to age at diagnosis: old(≥60 years, 90 cases), middle(40-59 years, 359 cases)and young patients(<40 years, 203 cases). The clinical data of 652 patients with PTC who were admitted to the Department of Thyroid Surgery of Beijing Hospital from December 2019 to December 2021 were retrospectively analyzed.The patients were divided into elderly group(≥60 years old, 90 cases), middle-aged group(40-59 years old, 359 cases)and young group(<40 years old, 203 cases). The clinical characteristics, ultrasound characteristics and invasion-related factors of patients in different groups were analyzed by statistical methods.Results:Compared with the young and middle-aged group, the elderly patients with PTC had a higher proportion of microcarcinoma(75.6%, 75.2%, 61.4%, χ2=13.054, P=0.001), less cervical lymph node metastasis(24.4%, 34.3%, 58.1%, χ2=41.650, P<0.001), and lower proportion of metastatic lymph nodes(0.08, 0.14, 0.24, χ2=40.618, P<0.001). There was no significant difference in tumor location and extra glandular invasion among the three age groups(35.56%, 36.2%, 38.4%, χ2=0.959, P=0.545). Conclusions:Compared with the young and middle-aged groups, PTC showed low invasiveness in the elderly population.In addition to surgical treatment, for elderly patients with low-risk clinical characteristics, it is worth performing a further study on whether careful observation or palliative treatment can be selected after comprehensive evaluation.

Analysis of influencing factors of clinical outcome after surgery and 131I treatment in patients with moderate-risk papillary thyroid cancer / 中华核医学与分子影像杂志

Objective:To investigate the clinical outcome after surgery and first 131I treatment in patients with moderate-risk papillary thyroid cancer (PTC), and analyze the relevant factors that affect the therapeutic effect. Methods:From January 2018 to April 2019, 135 patients (48 males, 87 females; age (42.7±11.1) years) with moderate-risk PTC in the Second Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. According to the 2015 American Thyroid Association (ATA) guidelines, patients were divided into excellent response (ER) group, inderteriminate response (IDR) group, biochemical incomplete response (BIR) group and structural incomplete response (SIR) group, of which IDR, BIR, SIR were collectively referred to as the non-ER group. χ2 test and Mann-Whitney U test were used to compare the general clinical features between the ER and non-ER groups, and then multivariate logistic regression analysis was performed. The predicted value of pre-ablation stimulated thyroglobulin (ps-Tg) to ER was assessed by ROC curve analysis. Results:The treatment responses of 94 patients were ER, and those of 41 were non-ER. The differences in tumor size (0.80(0.50, 1.10) vs 1.00(0.55, 1.50) cm; U=1 491.50, P=0.036), the number of metastatic lymph nodes (3(2, 5) vs 4(2, 12); U=1 422.00, P=0.015), metastatic lymph node size (0.50(0.30, 0.65) vs 0.50(0.30, 1.45) cm; U=1 396.50, P=0.013), metastatic lymph node involvement rate (50%(30%, 70%) vs 60%(50%, 85%); U=1 441.50, P=0.024), metastatic lymph node location (central/lateral: 76/18 vs 24/17; χ2=7.40, P=0.007) and ps-Tg level (2.1(0.8, 5.3) vs 14.0(3.2, 35.2) μg/L; U=680.00, P<0.001) were statistically significant between the ER and non-ER groups. Multivariate logistic regression analysis showed that ps-Tg (odds ratio ( OR)=1.200, 95% CI: 1.107-1.302, P<0.001) was an independent factor influencing ER. The cut-off value of ps-Tg for predicting ER was 7.38 μg/L, with the sensitivity and specificity of 68.3%(28/41) and 87.2%(82/94) respectively. Conclusion:Moderate-risk PTC patients with smaller tumor size, fewer metastatic lymph nodes, lower metastatic lymph node involvement rate, metastatic lymph nodes in central area, smaller metastatic lymph node size, and ps-Tg<7.38 μg/L have better therapeutic effect after initial 131I treatment.

Correlation analysis of BRAF V600E mutation with clinical pathological features and prognosis of differentiated thyroid cancer patients with different risk stratification / 中华核医学与分子影像杂志

Objective:To explore the relationship between B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation and clinical pathological features in patients with differentiated thyroid cancer (DTC), and to evaluate the value of BRAF V600E mutation in predicting the efficacy and follow-up of 131I treatment in DTC patients with different risk stratification. Methods:From January 2018 to June 2022, 893 DTC patients (205 males, 688 females, age (42.3±11.9) years) treated with 131I after total thyroidectomy in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Patients were divided into BRAF V600E mutation group ( n=729) and wild-type group ( n=164). According to the 2015 American Thyroid Association (ATA) guidelines, patients were divided into low-risk (39 cases), medium-risk (498 cases) and high-risk (356 cases), and the curative effect was divided into excellent response (ER) and non-excellent response (NER). The χ2 test, independent-sample t test and Mann-Whitney U test were used to compare differences between the two groups. Logistic regression analysis was performed to predict the influencing factors of treatment effect in DTC patients with different risk stratification. Results:The differences in age≥45 years, N stage, unilateral or bilateral DTC, multifocus, mode of operation, number and size of metastatic lymph nodes were statistically significant between BRAF V600E mutation group and wild-type group ( χ2 values: 4.45-17.40, t=-4.08, z=-3.08, all P<0.05). In medium- and high-risk stratification, the stimulated thyroglobulin (sTg) levels before and after 131I treatment were slightly higher in the BRAF V600E mutation group, while significantly sharp decreased of sTg and thyroglobulin antibody (TgAb) in wild-type group ( z value: from -9.30 to -2.65, all P<0.05). In medium- and high-risk stratification, 69.0%(60/87) and 64.3%(45/70) of BRAF V600E wild-type patients reached ER after 131I treatment, which were higher than those of mutant patients (57.4%(236/411) and 45.8%(131/286); χ2 values: 3.96, 7.39, P values: 0.046, 0.007). BRAF V600E mutation was the independent predictor affecting the efficacy of 131I treatment in DTC patients with medium- and high-risk stratification (odds ratio ( OR): 0.411 (95% CI: 0.196-0.864), 0.192 (95% CI: 0.096-0.384), P values: 0.019, <0.001). Conclusions:DTC patients with BRAF V600E mutation are related to the high invasiveness, and show poor improvement in biochemical indicators after initial 131I treatment. In addition, BRAF V600E mutation is an important factor in predicting the therapeutic effect of 131I in DTC patients with medium- and high-risk stratification.

Thoughts on the timing of targeted therapy initiation for thyroid cancer / 中华核医学与分子影像杂志

The treatment of persistent/recurrent and metastatic thyroid cancer and medullary thyroid cancer has made significant progress through the use of molecule-targeted therapy. While this approach has shown promise in improving patient outcomes and clinical symptoms, it also carries potential risks. The primary focus and challenge of targeted therapy is to optimize benefits while managing risks within predetermined thresholds. This review examines current targeted treatment practices in thyroid cancer and investigates the correlation between the timing of targeted therapy initiation and the patient benefits, aiming to lay the groundwork for subsequent research.

Clinical characteristics of patients with thyroid nodules and differentiated thyroid cancer with different body mass index / 中华核医学与分子影像杂志

Objective:To explore the association between body mass index (BMI) and the incidence of thyroid nodules, the clinical characteristics and efficacy evaluation of differentiated thyroid cancer (DTC), respectively.Methods:Clinical data of 1 375 healthy people (1 031 males, 344 females, age: (43.5±10.6) years) who underwent routine physical examination (PE) and 1 450 patients (490 males, 960 females, age: (44.3±12.4) years) with medium-high risk DTC in Tianjin Medical University General Hospital from April 2016 to July 2020 were analyzed retrospectively. PE and DTC patients were classified into underweight group (BMI<18.5 kg/m 2), normal weight group (18.5≤BMI<24.0 kg/m 2), overweight group (24.0≤BMI<28.0 kg/m 2) and obesity group (BMI≥28.0 kg/m 2) respectively. χ2 test was employed to analyze the relation between BMI and thyroid nodules (with/without), BMI and clinical characteristics and efficacy evaluation of DTC, respectively. Logistic regression analysis was used to analyze the independent risk factors for the occurrence of thyroid nodules and the aggressiveness of DTC. Results:Among PE, there were 779 cases with nodules, and 596 cases without nodules. Comparing with those without nodules, more overweight and obese were found in PE cases with nodules (42.1%(328/779) vs 37.2%(222/596), 24.5%(191/779) vs 20.5%(122/596); χ2=13.42, P=0.004). Higher risk of developing thyroid nodules was related with older age and lower thyroid stimulating hormone (TSH) level (odds ratio ( OR): 1.044, 0.919, 95% CI: 1.029-1.060, 0.845-0.999; P<0.001, P=0.046). People with high-risk nodules were more likely to be obese than those with intermediate and lower risk nodules (5/15 vs 24.3% (186/764); χ2=21.11, P<0.001). Among 1 450 DTC patients, comparing with patients with normal weight, patients in the overweight and obesity groups were more likely to have central regional lymph node metastasis ( OR: 1.418, 1.427, 95% CI: 1.075-1.870, 1.044-1.952; P values: 0.013, 0.026), and patients in obese group were with greater risk of lesions being bilateral ( OR=0.696, 95% CI: 0.519-0.934; P=0.016). BMI was not related with the efficacy evaluation of DTC ( χ2=9.13, P=0.425). Conclusions:The incidence of thyroid nodules in people with high BMI is higher. DTC patients with high BMI may have more aggressive incidence. But BMI has no correlation with the efficacy evaluation of DTC patients after treatment.

Efficacy and safety analysis of anlotinib in the treatment of distant metastatic radioactive iodine-refractory differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To investigate the efficacy and safety of anlotinib in distant metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:Retrospective analysis was performed on 17 patients with distant metastatic RAIR-DTC (6 males, 11 females, age: 57.0(45.5, 63.0) years) from Affiliated Hospital of Qingdao University between October 2018 and February 2023, including 13 patients receiving first-line treatment and 4 patients receiving second-line treatment with anlotinib. The changes of serum thyroglobulin (Tg) during the treatment of anlotinib, the changes of maximum diameter of the target lesion at the last follow-up compared with the diameter at baseline, the imaging efficacy, and treatment-related adverse events were analyzed. The serological and imaging effects of the first-line treatment group and the second-line treatment group were compared. The Fisher exact test was used to analyze the differences between groups.Results:The follow-up time of 17 patients was 17.3(9.5, 21.4) months, and the objective response rate (ORR) and disease control rate (DCR) were 7/17 and 16/17, respectively. There were no significant differences of ORR (6/13 vs 1/4; P=0.603) and DCR (13/13 vs 3/4; P=0.235) between the first-line and second-line treatment groups. The change rates of serum Tg at 3, 6 weeks and the last follow-up were -30.2%(-61.2%, -15.5%), -64.8%(-90.6%, -32.3%), and -85.8%(-96.1%, -50.7%), respectively. At the last follow-up, the change rate of maximum diameter of target lesions was -20.0%(-45.0%, -5.2%). The incidence of treatment-related adverse reactions was 14/17, and 2 patients (2/17) had grade 3 or above adverse reactions. Conclusion:Anlotinib shows superior efficacy with tolerable toxicity in the first-line treatment of distant metastatic RAIR-DTC, and hopefully plays an important role in second-line treatment for RAIR-DTC resistant to sorafenib.

Significance of BRAF V600E mutation in prediction of the efficacy of apatinib for radioactive iodine-refractory differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To investigate the significance of B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation in the prediction of response to apatinib treatment in advanced radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods:Twenty patients (10 males, 10 females, age: 51.5(46.3, 65.0) years) with advanced RAIR-DTC from Peking Union Medical College Hospital between March 2016 and March 2023 were retrospectively enrolled, and all patients were treated with apatinib and underwent genetic sequencing (including BRAF V600E and telomerase reverse transcriptase (TERT) promoter). The serological and imaging data, progression-free survival (PFS) and overall survival (OS) data were collected during apatinib treatment. The Kaplan-Meier survival analysis (log-rank test) was performed, and Mann-Whitney U test were used to analyze the differences of duration of response (DOR) between mutation group and wild-type group. Then univariate and multivariate Cox regression analyses were conducted. Results:The PFS (35.3 vs 9.2 months, χ2=7.53, P=0.006) and DOR (25.8(7.4, 35.2) vs 8.2(2.5, 13.4) months, U=23.00, P=0.046) of the BRAF V600E mutation group were longer than those of the wild-type group. Univariate Cox regression analysis showed that the BRAF V600E mutation group had better PFS benefit (hazard ratio ( HR)=0.22 (95% CI: 0.06-0.72), P=0.013), and the risk of disease progression or death in patients with lung metastasis and bone or brain metastasis was 3.06(95% CI: 1.10-8.54, P=0.033) times higher than that in patients with lung metastasis alone. Further, multivariate cox regression analysis showed that only BRAF V600E mutation was an independent predictor of PFS ( HR=0.23 (95% CI: 0.07-0.80), P=0.021), suggesting that RAIR-DTC patients with BRAF V600E mutation might have better efficacy of apatinib. There was no significant difference in PFS ( χ2=1.34, P=0.247) and OS ( χ2=0.19, P=0.664) between TERT promoter mutation group and wild-type group. Conclusion:RAIR-DTC patients with BRAF V600E mutation have longer PFS and DOR after apatinib treatment than those with BRAF V600E wild-type, suggesting that BRAF V600E may be a potential biomarker to guide tyrosine kinase inhibitor (TKI) therapy and help to refine TKI treatment indications.

Study of 68Ga-NODAGA-RGD PET/CT in predicting short-term efficacy of tyrosine kinase inhibitor in the treatment of distant metastatic differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To investigate the clinical application of 68Ga-cyclo( L-arginylglycyl- L-α-aspartyl- D-tyrosyl-N6-(((4, 7-bis(carboxymethyl)-1, 4, 7-triazonan-1-yl)acetyl))- L-lysyl) (NODAGA-RGD) PET/CT to evaluate short-term efficacy of tyrosine kinase inhibitor (TKI) in distant metastatic differentiated thyroid cancer (dmDTC). Methods:From October 2019 to March 2023, 13 dmDTC patients (5 males, 8 females; age: 68(65, 69) years) from Nanjing First Hospital were retrospectively enrolled, of which 9 were clinically confirmed as radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and 4 were dmDTC without radioactive iodine treatment. All patients underwent 68Ga-NODAGA-RGD PET/CT to assess neovascularization of the target lesions (TL), and the SUV max and target background ratio (T/B) were recorded. After 3 months of TKI treatment (anrotinib ( n=9) or apatinib ( n=4)), change rates of the maximum diameter of TL and thyroglobulin (Tg) were measured. The correlation of SUV max, T/B and the change rate of the maximum diameter of TL were analyzed by Spearman rank correlation analysis. ROC curve analysis was performed for the effectiveness of the T/B and TKI therapy, and the difference of the remission rate of lesions was analyzed by Fisher exact test. Results:In 13 patients, 36 TL were measured by 68Ga-NODAGA-RGD PET/CT with SUV max of 5.44(3.43, 7.56) and T/B of 5.25(4.50, 7.23). The change rate of the maximum diameter of TL was -30%(-39%, -21%) and the change rate of Tg was -68%(-96%, -52%). T/B was negatively correlated with the change rate of the maximum diameter of TL after TKI therapy ( rs=-0.46, P=0.005), while SUV max was not correlated with the change rate of the maximum diameter of TL ( rs=0.03, P=0.883). ROC curve analysis showed that the optimal cut-off value for T/B was 4.95, with the AUC of 0.698, the sensitivity of 87.5%, and the specificity of 60.0%. Compared to lesions with T/B<4.95, those with T/B≥4.95 showed higher remission rate (2/14 vs 63.6%(14/22); P=0.006). After 3 months of TKI treatment, the disease control rate was 12/13. Conclusion:68Ga-NODAGA-RGD PET/CT can effectively reflect tumor neovascularization, predict efficacy of TKI therapy, and provide powerful imaging evidence for TKI therapy in dmDTC.