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.

Correlation of 18F-sodium fluoride uptake and radiodensity in extraosseous metastases of medullary thyroid carcinoma

ABSTRACT Objective: Although 18F-sodium fluoride (18F-NaF) uptake is frequently observed in extraosseous metastases of medullary thyroid carcinoma (MTC) with calcification, it can also occur in metastatic sites without visible calcium deposition, leading to the hypothesis that visually undetectable calcium accumulation may be responsible for this uptake. The aim of this study was to indirectly support this hypothesis by analyzing the correlation between the degree of 18F-NaF uptake and radiodensity in extraosseous MTC metastases, since calcium deposition can increase attenuation even when not visually detectable. Subjects and methods: Extraosseous metastatic lesions of 15 patients with MTC were evaluated using 18F-NaF positron-emission tomography (PET)/computed tomography (CT) and segmented by levels of standardized uptake value (SUV). The correlation between mean SUV and mean Hounsfield unit (HU) values was assessed for the entire group of segments and for two subgroups with different mean HU values. Results: Very high correlations were observed between mean SUV and mean HU values for both the entire group of segments and the subgroup with a mean HU value greater than 130 (p = 0.92 and p = 0.95, respectively; p < 0.01). High correlation (p = 0.71) was also observed in the subgroup with mean HU values ranging from 20 to 130 (p < 0.01). Conclusion: The findings of the present study suggest that there is an association between 18F-NaF uptake and calcium deposition in extraosseous metastases of MTC, supporting the hypothesis that visually undetectable calcium accumulation may be responsible for 18F-NaF uptake in regions without visible calcium deposition.

Predictors of recurrence after total thyroidectomy in 1,611 patients with papillary thyroid carcinoma: postoperative stimulated serum thyroglobulin and ATA initial and dynamic risk assessment

ABSTRACT Objective: Despite a favorable prognosis, some patients with papillary thyroid carcinoma (PTC) develop recurrence. The objective of this study was to examine the impact of the combination of initial American Thyroid Association (ATA) risk stratification with serum level of postoperative stimulated thyroglobulin (s-Tg) in predicting recurrence in patients with PTC and compare the results with an assessment of response to initial therapy (dynamic risk stratification). Subjects and methods: We retrospectively analyzed 1,611 patients who had undergone total thyroidectomy for PTC, followed in most cases (87.3%) by radioactive iodine (RAI) administration. Clinicopathological features and s-Tg levels obtained 3 months postoperatively were evaluated. The patients were stratified according to ATA risk categories. Nonstimulated thyroglobulin levels and imaging studies obtained during the first year of follow-up were used to restage the patients based on response to initial therapy. Results: After a mean follow-up of 61.5 months (range 12-246 months), tumor recurrence was diagnosed in 99 (6.1%) patients. According to ATA risk, recurrence was identified in 2.3% of the low-risk, 9% of the intermediate-risk, and 25% of the high-risk patients (p < 0.001). Using a receiver operating characteristic curve approach, a postoperative s-Tg level of 10 ng/mL emerged as the ideal cutoff value, with positive and negative predictive values of 24% and 97.8%, respectively (p < 0.001). Patients with low to intermediate ATA risk with postoperative s-Tg levels < 10 ng/mL and excellent response to treatment had a very low recurrence rate (<0.8%). In contrast, higher recurrence rates were observed in intermediate-risk to high-risk patients with postoperative s-Tg ≥ 10 ng/mL and indeterminate response (25%) and in those with incomplete response regardless of ATA category or postoperative s-Tg value (38.5-87.5%). Using proportion of variance explained (PVE), the predicted recurrence using the ATA initial risk assessment alone was 12.7% and increased to 29.9% when postoperative s-Tg was added to the logistic regression model and 49.1% with dynamic risk stratification. Conclusions: The combination of ATA staging system and postoperative s-Tg can better predict the risk of PTC recurrence. Initial risk estimates can be refined based on dynamic risk assessment following response to therapy, thus providing a useful guide for follow-up recommendations.

CircSEMA6A upregulates PRRG4 by targeting MiR-520h and recruiting ELAVL1 to affect cell invasion and migration in papillary thyroid carcinoma

ABSTRACT Objective: As the most prevalent type of thyroid malignancy, papillary thyroid carcinoma (PTC) accounts for over 80% of all thyroid cancers. Circular RNAs (circRNAs) have been found to regulate multiple cancers, including PTC. Materials and methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to analyse RNA and protein levels. Fluorescence in situ hybridization (FISH) was used to detect the distribution of the target genes. Functional experiments and animal experiments were implemented to analyse the biological functions of target genes in vitro and in vivo. Luciferase reporter, RNA pulldown, RNA binding protein immunoprecipitation (RIP) and mRNA stability assays were used to probe the underlying mechanisms. Results: CircSEMA6Awas found to be upregulated in PTC tissues and cells, and its circular structure was verified. CircSEMA6A promotes PTC cell migration and invasion. Moreover, circSEMA6A functions as a competing endogenous RNA (ceRNA) to upregulate proline rich and Gla domain 4 (PRRG4) expression by sponging microRNA-520h (miR-520h). CircSEMA6A recruits ELAV1 to stabilize PRRG4 mRNA and drives PTC progression via PRRG4. Conclusion: CircSEMA6A upregulates PRRG4 by targeting miR-520h and recruiting ELAVL1 to affect the invasion and migration of PTC cells, offering insight into the molecular mechanisms of PTC.

Differentiated thyroid carcinoma: what the nonspecialists needs to know

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

Active surveillance is a feasible and safe strategy in selected patients with papillary thyroid cancer and suspicious cervical lymph nodes detected after thyroidectomy

ABSTRACT Objective: After initial treatment, up to 30% of patients with papillary thyroid cancer (PTC) have incomplete response, mainly cervical lymph node (LN) disease. Previous studies have suggested that active surveillance (AS) is a possible option for these patients. Our aim was to report the results of AS in patients with PTC and cervical LN disease. Materials and methods: In this retrospective observational study, we included adult patients treated and followed for PTC, who presented with cervical LN disease and were managed with AS. Growth was defined as an increase ≥ 3mm in either diameter. Results: We included 32 patients: 27 (84.4%) women, age of 39 ± 14 years, all initially treated with total thyroidectomy, and 22 (69%) with therapeutic neck dissection. Cervical LN disease was diagnosed 1 year (0.3-12.6) after initial management, with a diameter of 9.0 mm (6.0-19.0). After a median AS of 4.3 years (0.6-14.1), 4 (12.5%) patients had LN growth: 2 (50%) of whom were surgically removed, 1 (25%) was effectively treated with radiotherapy, and 1 (25%) had a scheduled surgery. Tg increase was the only predictive factor of LN growth evaluated as both the delta Tg (p < 0.0366) and percentage of Tg change (p < 0.0140). None of the included patients died, had local complications due to LN growth or salvage therapy, or developed distant metastases during follow-up. Conclusions: In selected patients with PTC and suspicious cervical LNs diagnosed after initial treatment, AS is a feasible and safe strategy as it allows effective identification and treatment of the minority of patients who progress.

Golgi Transport 1A Promotes Cell Proliferation and Metastasis of Papillary Thyroid Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo investigate the expression level of Golgi transport 1A （GOLT1A） in thyroid carcinoma and its effects on the proliferation， migration， invasion， and epithelial-mesenchymal transition （EMT） of thyroid carcinoma cells. MethodsThe expression of GOLT1A in thyroid carcinoma was analyzed online by tumor immune estimation resource （TIMER）， the University of Alabama at Birmingham cancer data analysis portal （UALCAN）， gene expression profiling interactive analysis 2 （GEPIA2）. The expression level of GOLT1A in thyroid carcinoma cells was detected by real-time fluorescence quantitative polymerase chain reaction （RTFQ-PCR） and western blot. Cell counting kit-8 （CCK-8） assay， colony formation assay， and transwell assay were used to detect the effects of GOLT1A expression on the proliferation， migration， and invasion of thyroid carcinoma cells. Western blot assay was used to detect the effect of GOLT1A on the expression of EMT-related genes including E-cadherin， vimentin， and N-cadherin. ResultsThe online analysis of GEPIA2， TIMER， and UALCAN showed that the expression of GOLT1A was higher in thyroid carcinoma than in normal tissues， and the expression of GOLT1A in thyroid carcinoma cells was significantly higher than in normal control cells. Knockdown of GOLT1A inhibited TPC1 cell proliferation， migration， and invasion. The expression of E-cadherin increased and the expressions of N-cadherin and vimentin decreased in GOLT1A knockdown TPC1 cells. Overexpression of GOLT1A promoted BCPAP cell proliferation， migration， and invasion. The expression of E-cadherin decreased and the expressions of N-cadherin and vimentin increased in GOLT1A overexpression BCPAP cells. ConclusionGOLT1A is highly expressed in thyroid carcinoma and can promote the proliferation， migration， and invasion of thyroid carcinoma cells.

Comparison of New and Old Versions of Guidelines for Diagnosis and Treatment of Thyroid Nodules and Differentiated Thyroid Carcinoma in China from A Surgical Perspective / 肿瘤防治研究

The set of guidelines for the diagnosis and treatment of thyroid nodules and differentiated thyroid cancer (the second edition) was published in 2023 in China. Based on the first (2012) edition, the current set was revised jointly by nearly 100 experts in endocrinology, thyroid surgery, oncology, nuclear medicine, ultrasound medicine, and pathology from seven national societies for one year. The new version of the guideline is still divided into two parts, namely, thyroid nodules and differentiated thyroid cancer. The writing mode of asking clinical questions, explaining and giving recommendations is adopted, and a total of 117 recommendations are provided. This article aims to compare the variations in the differentiation of benign and malignant thyroid nodules and surgical treatment of differentiated thyroid cancer between the new and old versions from the perspective of surgery. The author's own understanding and experiences are also discussed.

Comprehensive analysis of clinicopathologic and sonographic features in thyroid cancer with skip lymph node metastasis: establish and assessment of a prediction nomogram

Abstract Lateral Lymph Node Metastasis (LLNM) is common in Papillary Thyroid Carcinoma (PTC) and is associated with a poor prognosis. LLNM without central lymph node metastasis as skip metastasis is not common. We aimed to investigate clinicopathologic and sonographic risk factors for skip metastasis in PTC patients, and to establish a nomogram for predicting the possibility of skip metastasis in order to determine the therapeutic strategy. We retrospectively reviewed the data of 1037 PTC patients who underwent surgery from 2016 to 2020 at a single institution. Univariate and multivariate analyses were used to identify the clinicopathologic and preoperative sonographic risk factors of skip metastasis. A nomogram including the risk factors for predicting skip metastasis was further developed and validated. The incidence of skip metastasis was 10.7%. The univariate and multivariate analyses suggested that gender (p = 0.001), tumor location (p = 0.000), extrathyroidal extension (p = 0.000), and calcification (p = 0.000) were independent risk factors. For papillary thyroid microcarcinoma, tumor location (p = 0.000) and calcification (p = 0.001) were independent risk factors. A nomogram according to the clinicopathologic and sonographic predictors was developed. The receiver operating characteristic curve indicated that AUC was 0.824 and had an excellent consistency. The calibration plot analysis showed a good performance and clinical utility of the model. Decision curve analysis revealed it was clinically useful. A nomogram for predicting the probability of skip metastasis was developed, which exhibited a favorable predictive value and consistency. For the female PTC patient, tumor located at the upper pole is more likely to have skip metastasis. Surgeons and sonographers should pay close attention to the patients who have the risk factors. Evidence level: This article's evidence level is 3. Level 3 evidence is derived from nonrandomized, controlled clinical trials. In this study, patients who receive an intervention are compared to a control group. Authors may detect a statistically significant and clinically relevant outcome.

Predictive factors and risk analysis of recurrent laryngeal nerve invasion in papillary thyroid carcinoma ≤ 1 cm

ABSTRACT Objective: The recurrent laryngeal nerve (RLN) may be involved by papillary thyroid carcinoma ≤ 1 centimeter (PTC ≤ 1 cm). Current study investigated the predictive factors of RLN invasion in PTC ≤ 1 cm, the risk factors of disease recurrence in RLN invaded cases and the results of surgical management for RLN invasion. Materials and methods: Data of 374 PTC ≤ 1 cm patients were retrospectively collected. We performed univariate and multivariate analysis to identify predictive factors of RLN invasion and risk factors of disease recurrence. The abilities of factors in predicting RLN invasion were evaluated. Surgical outcomes and recurrence free survival (RFS) of patients were analyzed. Results: A total of 28 patients suffered RLN invasion, among which seven had disease recurrence. Preoperative vocal cord palsy (VCP), gross extrathyroidal extension, larger tumor size and tumor on the dorsal side of thyroid were verified as predictive factors of RLN invasion. RLN involved patients had poorer RFS, but better than those who also had upper-aerodigestive tract invasion. Upper-aerodigestive tract invasion, lateral neck lymph nodes metastasis (LNM) and BRAF V600E mutation were independent risk factors of disease recurrence in RLN invaded cases. Tumor shaving showed better RLN function preservation without increasing recurrent risk. Conclusions: Current study confirmed the rarity of RLN invasion in PTC ≤ 1 cm. Various aggressive features were verified as predictive factors of RLN invasion. Tumor shaving showed superiority in preserving nerve function without increasing recurrent risk. Special attentions should be paid for disease recurrence when RLN invasion accompanied by upper-aerodigestive tract invasion, lateral neck LNM or BRAF V600E mutation.

Quilotórax y abdomen agudo quiloso en el contexto de un vaciamiento ganglionar cervical / Chylothorax and chyloperitoneum in the setting of neck lymph node dissection

RESUMEN La presencia de quilotórax y de abdomen agudo quiloso luego de un vaciamiento ganglionar cervical izquierdo es una complicación muy poco frecuente. Se presenta el caso de una mujer de 24 años a quien se le realizó un vaciamiento ganglionar cervical bilateral por metástasis de carcinoma de tiroides. El segundo día del posoperatorio presentó dolor abdominal. Los estudios complementarios permitieron diagnosticar quilotórax y abdomen agudo quiloso, posiblemente como consecuencia de la ligadura inadvertida del conducto torácico. Se realizó el tratamiento médico y el drenaje percutáneo de ambas cavidades. Debido a buena evolución se indicó el alta hospitalaria con el drenaje abdominal, y continuar el seguimiento en forma ambulatoria. El tratamiento médico controlado para las lesiones del conducto torácico constituye la primera opción. En caso de mala evolución se debe pensar en la resolución quirúrgica sin demora.

ABSTRACT Chylothorax and chyloperitoneum after left lymph node dissection are rare complications. We report the case of a 24-year-old woman with a history of total thyroidectomy with bilateral lymph node dissection for metastases of papillary thyroid carcinoma. On postoperative day 2 the patient presented generalized abdominal pain. The complementary tests allowed for the diagnosis of chylothorax and chyloperitoneum. Medical treatment was started and percutaneous drainage of both cavities. The patient had favorable outcome and was discharged with the abdominal drain and indication of follow-up in the outpatient clinic. Supervised medical treatment for thoracic duct injuries constitute the first treatment option. Surgery should not be delayed in case of poor outcome.

Risk of malignancy in thyroid nodules classified as Bethesda categories III, III - subcategories and IV: 2.5 years study

Introduction: Thyroid fine-needle aspiration cytology (FNAC) has gained significance as a quick, safe, and relatively simple method to differentiate malignant from benign thyroid nodules and is regarded as the gold-standard first-line diagnostic test in the evaluation of thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established a standardized, category-based reporting system for thyroid FNAC with each category having an implied cancer risk. However, the optimal management of thyroid nodules in the Bethesda III and IV categories is controversial, given the variable malignancy rates. Aims/Objectives: (1) Analysis of the cytomorphological characteristics of patients with categories III and IV of “TBSRTC.” (2) Assessment of risk of malignancy of TBSRTC category III, IV, and substratification of TBSRTC category III. Materials and Methods: A retrospective and prospective study of cases categorized under TBSRTC as category III and IV at a tertiary-care center. Cytological along with their histological results were compared. Results: We identified an overall malignancy rate of 33% for nodules belonging to Bethesda category III and a malignancy rate between 19% and 33% for Bethesda category IV. Also, a significantly higher risk of malignancy in subcategories with nuclear and architectural atypia (66.6%) than only architectural atypia (28.7%). Conclusion: Although surgery is recommended in most of these cases, cytomorphology helps to predict the final histopathological findings with greater accuracy. Substratification of category III into subgroups may help reduce the heterogeneity of the atypia of undetermined significance/follicular lesion of undetermined significance category and more.

Iodine nutritional status is not a direct factor in the prevalence of the BRAFV600E mutation in papillary thyroid cancer

ABSTRACT Objectives: Papillary thyroid carcinoma (PTC) accounts for approximately 85%-90% of all thyroid cancers. Of the iodine-metabolizing genes, BRAFV600E is a highly specific target for PTC and may have a reciprocal causative relationship with iodide-metabolizing genes. Materials and methods: In this study, we performed a data analysis of selected quantitative studies to determine the relationship between iodine nutritional status and the prevalence of the BRAF600E mutation in patients with PTC. Five studies were selected for meta-analysis based on the selection criteria. Results: A total of 2,068 patients were divided into three groups: low (urinary iodine concentration [UIC] < 100 μg/L), adequate (UIC 100-200 μg/L), and high (UIC ≥ 200 μg/L). The results were obtained using RevMan software, and the pooled odds ratios (ORs) were calculated using Mantel-Haenszel statistics with a 95% confidence interval (CI). The OR for the prevalence of the BRAFV600E mutation between the high and adequate groups was 1.25 (95% CI 0.64-2.43, p = 0.51), and the OR between the low and adequate groups was 0.98 (95% CI 0.42-2.31, p = 0.96). The BRAFV600E mutation risk did not change significantly at different levels of iodine nutrition (p = 0.33) in statistical analyses. Conclusion: We conducted preliminary research on dietary iodine intake and the BRAFV600E mutation in PTC. The results suggested that abnormal iodine intake might not directly influence the prevalence of the BRAFV600E mutation in these patients. Further research into the associations between dietary iodine intake and the BRAFV600E mutation in PTC, including the underlying mechanisms, is required.

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.

Correlation analysis of TPO antibody and thyroglobulin antibody with clinicopathological features of PTC / 中华内分泌外科杂志

Objective:To explore and analyze the correlation between thyroid peroxidase (TPO) and thyroglobulin (Tg) in patients with papillary thyroid carcinoma (papillary thyroid carcinoma, PTC) and to provide a more reasonable plan for the clinical diagnosis and treatment of patients.Methods:A retrospective analysis was made of 142 PTC patients who underwent surgical resection from Jun. 2019 to Jun. 2022 in the Oncology Department of Wenzhou Hospital of Traditional Chinese Medicine. 115 patients were selected, including 25 males (21.74%), and 90 females (78.26%), and the average age was (43.48±9.74) years old. The medical records, pathology reports, and demographic characteristics and pathological characteristics were collected. Immunohistochemical staining was used to detect the expression of TPO and Tg in PTC tissues, which were divided into positive and negative groups. Multifactorial Logistic regression analysis was used to analyze its relationship with clinicopathological characteristics and prognosis of patients.Results:The negative rate of TPO was 95.45% (105 cases). Univariate analysis showed that the tumor diameter ( t=5.746), lymph node metastasis, and the proportion of PT1 patients were significantly different between the two groups ( P<0.05), the TPO negative group was significantly higher than the positive group. Multivariate logistic regression analysis found that tumor diameter, lymph node metastasis, and proportion of PT1 patients were independent factors (95% CI=2.367-5.365, 1.101-2.738, 1.103-2.589, P<0.05). The positive rate of Tg was 77.41% (89 cases). Univariate analysis showed the proportion of people with BMI ≥ 25 ( χ2=11.180), tumor diameter ( t=2.117), and intracapsular invasion ( χ2=8.354), extrathyroidal invasion, lymph node metastasis ( χ2=27.740), and proportion of PT1 patients were significantly different between the two groups ( P<0.05). Multivariate logistic regression analysis found BMI≥25, intracapsular invasion, extrathyroidal invasion, lymph node metastasis, proportion of PT1 patients were independent factors affecting Tg in patients with PTC (95% CI=3.845-11.735, 1.485-2.983,1.171-2.762,4.083-16.526,1.003-2.174, P<0.05). There was a negative correlation between the expression of TPO and Tg in PTC ( r=-0.498, P<0.001) . Conclusion:TPO and Tg are highly correlated with tumor lymphatic metastasis, pathological grade, tumor diameter and tumor invasion range in patients with papillary thyroid carcinoma, and the expression of the two is negatively correlated, which can be used as effective indicators for evaluating the prognosis of patients.

Clinical value of thrombologram in predicting the risk of hemorrhage after thyroid cancer surgery and guiding blood transfusion therapy / 中华内分泌外科杂志

Objective:To explore the value of thromboela-stogram (TEG) in predicting the risk of bleeding in patients undergoing thyroid cancer surgery and guiding blood transfusion therapy.Methods:46 patients with hemorrhage after thyroid cancer surgery in General Surgery Department of the Second Hospital of Shanxi Medical University from Sep. 2021 to Sep. 2022 were selected as the hemorrhage group, including 12 males and 34 females. The age ranged from 18 to 76 years old, with an average age of (45.39±8.64). A total of 46 patients with no postoperative bleeding during the same period were selected as control group, including 9 males and 37 females. The average age was (43.86±9.12) years, ranging from 18 to 75 years. Postoperative TEG parameters, thrombin time (fibrinogen), fibrinogen (FIB), prothombin time (PT), thrombin time (thrombin time, TT), activited partial thomboplastin time (APTT) ], Spearman correlation coefficient was used to analyze the correlation between TEG parameters, coagulation parameters and postoperative blood loss. The value of TEG parameters and coagulation indexes in predicting bleeding was evaluated by receiver operating characteristic (ROC) curve.Results:R value (9.81±1.39) min, K value (3.52±0.94) min, PT value (14.12±1.98) s, TT value (21.36±3.21) s and APTT value (40.29±7.18) s in hemorrhage group were higher than those in control group (7.09±1.12) min and 2.75±0.81) min, (12.86±1.74) s, (19.71±2.53) s, (36.15±6.52) s, MA value (51.67±5.13) mm, Angle (47.06±9.24) °, FIB (1.95±0.64) g/L were lower than control group (57.76±6.05) mm, (58.29±10.28) °, (2.41±0.89) g/L (t 1=10.335, t 2=4.209, t 3=3.242, t 4=2.738, t 5=2.895, t 6=5.207, t 7=5.510, t 8=2.846, all P<0.05) ; R-value (11.02±1.26) min and K-value (4.16±0.93) min in patients with high blood (≥10 ml) bleeding group were higher than those in patients with low bleeding (<10 ml) (9.28±1.19) min and (3.24±0.89) min. MA value (48.04±5.01) mm, Angle (42.15±9.14) ° were lower than those of patients with hypohemorrhage (53.26±5.29) mm, (49.21±9.53) ° (t 1=4.484, t 2=3.183, t 3=3.127, t 4=2.340, P<0.05). The amount of blood loss after thyroid cancer surgery was positively correlated with R value and K value, and negatively correlated with MA value and Angle (r 1=0.421, r 2=0.335, r 3=-0.318, r 4=-0.306, all P<0.05). The area under the curve (AUC) of R value, K value, MA value and Angle predicted perioperative bleeding of thyroid cancer surgery was>0.7. R value (7.13±1.15) min, K value (2.81±0.82) min, PT (13.01±1.76) s, TT (20.03±2.60) s, APTT (37.12±6.64) s after treatment were lower than those before treatment (9.81±1.39) min, (3.52±0.94) min, (14.12±1.98) s, (21.36±3.21) s, (40.29±7.18) s, MA value (56.89±5.94) mm, Angle (56.73±9.86) °, FIB (2.35±0.85) g/L were higher than those before treatment (51.67±5.13) mm, (47.06±9.24) °, (1.95±0.64) g/L (t 1=10.076, t 2=3.860, t 3=2.842, t 4=2.184, t 5=2.198, t 6=4.511, t 7=4.854, t 8=2.550, all P<0.05) . Conclusion:TEG parameters R value, K value, MA value and Angle have certain predictive efficacy in predicting bleeding risk of patients undergoing thyroid cancer surgery, and can guide clinical transfusion therapy.

Advances in diagnosis and treatment of medullary thyroid carcinoma complicated with papillary carcinoma / 中华内分泌外科杂志

Thyroid cancer is the most common malignant tumor of the endocrine system, and its incidence is increasing year by year showing younger trend. The pathological types of thyroid cancer are papillary carcinoma, follicular carcinoma, medullary carcinoma and undifferentiated carcinoma. Medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) are the two common types of thyroid cancer. Since MTC and PTC have different biological origins, invasiveness and prognosis. Therefore, the occurrence of both medullary carcinoma and papillary carcinoma is very rare and rarely reported in China and abroad and the treatment is challenging. In this paper, we review the pathogenesis, ancillary tests, diagnosis and treatment of this disease, with the aim of providing reference for clinical treatment of patients with medullary thyroid carcinoma complicated by papillary carcinoma.

Value of CT-based model in differential diagnosis of papillary thyroid carcinoma / 中华内分泌外科杂志

Objective:To evaluate the differential diagnosis of papillary thyroid carcinoma (PTC) based on CT signs.Methods:Retrospective analysis was performed on 156 patients with PTC confirmed by surgery and pathology in the Imaging Department of Jinhua Hospital Affiliated to Zhejiang University College of Medicine from Jan. 2017 to Jan. 2022 as PTC group, and 132 patients with nodular goiter (NG) as NG group. There were 112 females and 45 males in the PTC group. The age was (49.32±3.25) years. There were 104 females and 52 males in NG group. The age was (50.12±3.27) years. Preoperative plain and contrast-enhanced CT scans were performed to analyze the features of the images, and univariate analysis was performed on the morphologic features, high tension, plain "bite cake sign" , enhanced "bite cake sign" , microcalcification, blurred/reduced scope after enhancement, nodule density, and asymmetric diffuse enlargement of thyroid gland. Statistically significant factors were included in the multivariate Logistic regression analysis, and the differential model of PTC was established according to the selected risk factors. The value of the model in the differential diagnosis of PTC was evaluated by ROC curve.Results:The percentages of irregular shape, no high tension, plain scan "bite cake sign" , enhanced "bite cake sign" , microcalcification, enhanced blur/reduced scope, uniform nodule density, completely slightly low tissue density, no cystic degeneration, and asymmetric thyroid diffuse enlargement in PTC group were higher than those in NG group ( χ2=161.014, 3.387, 95.885, 151.331, 60) . 200, 18.104, 105.260, 16.855, 89.064, 16.913, P<0.05) , suggesting that the above CT signs had important diagnostic value in differentiating PTC and NG. Among the single CT signs, plain scan "bite cake sign" had the highest sensitivity, specificity and accuracy. The sensitivity of PTC diagnosis combined with other signs gradually decreased, while the specificity gradually increased. At the same time, plain scan "bite cake sign" and microcalcification signs had high specificity in PTC identification, and the specificity of PTC identification reached 100.00% when any 4 or more signs were present. Multivariate Logistic regression analysis. The results showed that irregular morphology ( OR=15.831, 95% CI: 7.444-33.670) , high tension ( OR=0.162, 95% CI: 0.108-0.242) , plain scan "bite cake sign" ( OR=5.601, 95% CI: 2.691-11.659) , microcalcification ( OR=4.031, 95% CI: 2.062-7.880) , edge blur/range reduction after enhancement ( OR=4.761, 95% CI: 3.126-7.260) , uniform density of nodules ( OR=4.778, 95% CI: 3.299-6.290) and increased asymmetric diffusion ( OR=3.758, 95% CI: 1.911-7.391) were important signs for distinguishing NG from PTC ( P<0.05) . The above factors were incorporated into the Logistic regression equation to construct the model, and then the ROC curve was drawn. The results showed that the area under the curve of the model established based on CT signs was 0.94 (0.925-0.983) , and the sensitivity and specificity were 90.37% and 91.45%, respectively. Conclusions:In CT signs, irregular shape, high tension, "biting cake sign" on plain scan, microcalcification, blurred edge/scope reduction signs after enhancement, and uniform nodule density are important signs for differentiating papillary thyroid carcinoma from nodular goiter. The constructed model has good predictive value for identifying papillary thyroid carcinoma.

Relationship between UE and CEUS indexes and the expression of invasion genes and proliferation genes in differentiated thyroid cancer tissue / 中华内分泌外科杂志

Objective:To study the diagnostic value of ultrasonic elastography (UE) CEUS in differentiated thyroid cancer (DTC) and its correlation with invasive gene and proliferative gene expression in DTC tissue.Methods:100 DTC patients who were treated in the Ultrasound Department of Zhuji People’s Hospital of Zhejiang Province from Jan. 2019 to Jan. 2022 were retrospectively selected and included in the TC group, and 100 thyroid adenoma patients who were treated during the same period were included in the thyroid adenoma group. UE and CEUS tests were performed on all patients, and the expression levels of proliferative and invasive genes in tumor tissues were measured. Time to peak (TTP) , average time of contrast medium passage (MTT) and peak intensity (PI) were recorded. DTC patients were divided into groups according to the blue area ratio, elastic ratio of lesions, optimal ROC truncation value of TTP, MTT and PI, that is, elastic value > 1.66, blue area ratio > 51.21%, PI≤17.11dB, MTT≤36.39s, TTP≤18.90s were group A, and vice president was Group B. SPSS 19.0 was used for data analysis, and P < 0.05 was considered to be statistically significant. Results:The blue area ratio and elastic ratio of lesions in TC group were higher than those in thyroid adenoma group ( P < 0.05) , while TTP, MTT and PI in TC group were lower than those in thyroid adenoma group ( P < 0.05) . There were statistically significant differences in blue area ratio, elastic ratio of lesions, TTP, MTT and PI among TC groups with different clinical stages, capsule invasion and lymph node metastasis ( P<0.05) . ROC curve was drawn. The AUC of DTC combined with blue area ratio, elastic ratio of lesions, TTP, MTT and PI was the highest, the specificity of combined detection was 86.37%, and the detection sensitivity was 80.16%. Compared with thyroid adenoma group, Xklp2 target protein (TPX2) , chemokine receptor 4, CXCR4) and polymetalloproteinase-9 (ADAM9) gene expression levels were higher, but TDCD4 gene expression levels were lower ( P<0.05) . The expression levels of TPX2, CXCR4 and ADAM9 genes in group A were higher than those in group B ( P<0.05) , and the programmed death factor 4 (PDCD4) gene in group A was lower than that in group B ( P<0.05) . According to Pearson linear analysis, the blue area ratio and elastic ratio of lesions were positively correlated with the expression levels of TPX2, ADAM9 and CXCR4 genes in DTC tissues, and inversely correlated with the expression levels of PDCD4 genes in DTC tissues ( P<0.05) . The expression levels of TPX2, ADAM9 and CXCR4 genes in TTP, MTT and PI were inversely proportional to the expression levels of PDCD4 genes in DTC patients ( P<0.05) . Conclusion:The combination of blue area ratio, elastic ratio of lesions, TTP, MTT and PI has good diagnostic value for DTC, and the blue area ratio, elastic ratio of lesions, TTP, MTT and PI are correlated with the expression levels of invasive genes and proliferating genes in tumor tissues.

Expression of HLA-G in the peripheral blood and cancerous tissues of patients with papillary thyroid cancer / 中华内分泌外科杂志

Objective:To examine the expression of human leukocyte antigen G (HLA-G) in the peripheral blood and cancerous tissues of patients with papillary thyroid carcinoma (PTC) .Methods:The expression of soluble HLA-G (sHLA-G) in the peripheral blood of 50 individuals with PTC (PTC group) , 25 patients with benign thyroid tumors (BTT group) from Department of Thyroid and Breast Surgery, Beilun branch of the First Affiliated Hospital of Zhejiang University and 20 healthy controls (healthy control group) from physical examination center was assessed by ELISA. Immunohistochemical examination of HLA-G levels was also performed on tissue specimens from patients in the PTC and BTT groups, and their correlation with clinicopathological features of thyroid cancer was analyzed. SPSS 19.0 was used for statistical analysis. The measurement data of normal distribution were tested by two independent samples t test. Chi square test was used to compare the rates between the two groups. Results:The sHLA-G expression in peripheral blood was 21.33 (±5.54) , 22.73 (±4.99) , and 18.29 (±4.43) ng/mL in the preoperative PTC, BTT, and healthy control groups, respectively. Compared to the healthy group, sHLA-G levels were considerably higher in the PTC and BTT groups, with statistically significant differences (totally P < 0.05) . There was no significant difference in statistically sHLA-G levels between the BTT and PTC groups ( P > 0.05) . The positive HLA-G expression rate in PTC tissues was 78% (39/50) . There was no evidence of HLA-G expression in common tissues adjacent to PTC. HLA-G was not expressed in benign tumors. HLA-G was linked with the PTC tumor diameter, and the rate of positive expression was considerably greater with tumor diameters >1 cm than with those ≤1 cm ( P<0.05) . The rate of HLA-G positive expression was not significantly correlated with sex, age, multiple foci, extra-glandular invasion, metastasis of lymph nodes, or the TNM stage in PTC individuals ( P > 0.05) . Conclusions:HLA-G is significantly expressed at high levels in PTC tissues, is correlated with the tumor diameter, and may probably have a significant role in this disease. Peripheral blood sHLA-G may be associated with thyroid tumorigenesis, and its value in PTC requires further verification.