Evaluation of epithelial-to-mesenchymal transition and Ki-67 index in aggressive papillary thyroid cancer.

OBJECTIVES: The present study aims to characterize immunohistochemical features of markers associated with Epithelial-Mesenchymal Transition (EMT) and proliferative activity that could lead to death in Papillary Thyroid Cancer (PTC). METHODS: Clinical data and tumor material were retrospectively collected. The patients were separated into death from PTC (Group 1), metastatic cases with indolent behavior (Group 2) and non-metastatic indolent PTC (Group 3). Immunohistochemical assessment of E-cadherin, ß-catenin, Vimentin, ZEB-1 and Ki-67 was performed in each tumor and a semiquantitative estimation of the percentage of expression was fulfilled on the best marking area at high of the tumor invasion front. RESULTS: 31 patients were included, 15 that died from PTC (Group 1), 6 in Group 2 and 10 in Group 3. The proliferative marker Ki-67 showed a significant difference in its expression in the tumor invasion front between the groups, specifically between groups 1 and 3 (p = 0.006). On the other hand, EMT-related immunohistochemical markers did not show significant difference in their percentage of expression, since loss of E-cadherin, ß-catenin and Vimentin was observed in most cases at the invasion front. CONCLUSION: Patients that died from PTC had a significantly higher Ki-67 labelling index compared to patients with indolent disease (cutoff of 11%). Ki-67 may have a role as a prognostic marker and could be considered for routine use in PTC.

The Association between Metals and Thyroid Cancer in Puerto Rico-A National Health and Nutrition Examination Survey Analysis and Ecological Study.

Thyroid cancer rates have risen globally over the past four decades, with Puerto Rico experiencing a particularly pronounced increase. This may be linked to higher metal exposure, as some metals are endocrine disruptors and carcinogens. Currently, certain regions of Puerto Rico have Superfund programs because of high concentrations of metals in the soil. Therefore, we investigated the association between thyroid cancer incidence and three metals (lead, cadmium, and mercury) with known endocrine-disrupting properties and increased levels in soil samples in Puerto Rico. We used the National Health and Nutrition Examination Survey (NHANES) data for heavy metal levels and the thyroglobulin antibody (TgAb) as a thyroid cancer marker. Additionally, we performed an ecological study using data from the Environmental Protection Agency (EPA) report on Metals from Natural and Anthropogenic Sources in Puerto Rico Soils and data from the Puerto Rico Central Cancer Registry on age-adjusted thyroid cancer incidence rates from 2015 to 2019. Through NHANES analysis, we found a significant negative association between mercury and TgAb. Through our ecological study, we observed higher thyroid cancer incidence rates and increased metal levels in the soil in the northern parts of Puerto Rico. Our heterogenous results necessitate further research on this topic.

Impact of a simple informative leaflet on Brazilian doctors' attitudes towards active surveillance of thyroid microcarcinomas.

Introduction: Active surveillance (AS) is increasingly recognized as an appropriate strategy for selected patients with papillary thyroid microcarcinomas (PTMC). However, some factors, including physician-related ones, hinder its widespread adoption. Methods: To explore the prevailing barriers and the impact of information on attitudes towards AS implementation, we developed a questionnaire that was completed before and after reading a simple information leaflet by 317 doctors working in different work environments. This leaflet provides information about the overdiagnosis of PTMC, the concept of AS, results of early studies, and main advantages and disadvantages of AS. Results: We observed a greater resistance to AS among male physicians who were more likely to maintain the initial recommendation for surgery or referral to a head and neck surgeon than female physicians (77 % vs. 46 %, p = 0.01), regardless of their medical specialty. Fear of disease progression and of the patient losing follow-up were the main concerns. Reading the educational material significantly increased the number of physicians who endorsed AS as an initial approach to PTMC without risk factors from 14 % to 34 % (p < 0,001). This change in attitude was even more significant when doctors were confronted with a case of PTMC in an elderly patient. Gender, medical specialty, age range and academic environment were the factors that were determinants on the influence of the informative leaflet on the decision-making. The leaflet also increased the number of doctors who considered themselves capable of dealing with this patient profile; however, 17 % declared that the place where they worked would not be able to meet the need for periodic assessments and necessary examinations. This was particularly true for the 20 % of the professionals working in rural areas. Conclusion: A simple educational leaflet with basic information presented via social media increased the number of Brazilian physicians who endorsed AS for PTMC management and proved to be a facilitating tool for understanding and accepting it. Our results suggest that this method can be easily extended to larger population.

Association between papillary thyroid cancer and primary aldosteronism in individuals with hypertension.

BACKGROUND: Aldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group. METHODS: We conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT). PA was investigated in 137 patients with PTC and HT. The control group included 137 (1:1) age, sex-, and body mass index (BMI)-matched individuals with HT. We conducted a secondary analysis in which the controls were also matched according to HT stage. RESULTS: The prevalence of PA was 29.20% (95% confidence interval [CI], 21.91%-37.68%) in the PTC group and 20.44% (95% CI, 14.22%-28.35%) in the controls not matched for HT stage (p = 0.093). Although the PA prevalence was similar in both groups, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group (23%) compared to the hypertensive controls (73%, p < 0.001). After matching the controls by HT stage, the prevalence of PA in the PTC group was significantly higher compared to the hypertensive controls (9.56%; 95% CI, 5.39%-16.1%, p < 0.0001). In the multivariable analysis, PTC was independently associated with PA in both unmatched hypertensive individuals (odds ratio [OR] 4.74; 95% CI, 2.26-10.55; p< 0.001) and in those matched for HT stage (OR 5.88, 95% CI, 2.79-13.37; p< 0.001). CONCLUSION: PTC was an independent variable associated with a diagnosis of PA in hypertensive individuals. Therefore, we propose the association between PTC and HT as a new recommendation for PA screening regardless of HT severity.

Exploring the link between inflammatory myopathies and cancer: A comprehensive retrospective analysis in a Colombian cohort.

BACKGROUND: This study investigates the association between inflammatory myopathies (IM), and their correlation with cancer. There are several potential causes behind the association of cancer and inflammatory myopathies. The positivity of specific antibodies for myositis plays a significant role. Our objective is to describe cancer and inflammatory myopathies in Colombia, focusing on demographics, clinical characteristics, and laboratory data. METHODS: We retrospectively analyzed 112 IM patients diagnosed at Fundación Valle del Lili in Cali, Colombia, the cases met the EULAR/ACR criteria. Data included demographics, clinical signs, laboratory findings, and malignancy. Malignancy associations were explored using logistic regression. The survival analysis was assessed using Kaplan-Meier curves and the Log-Rank test. RESULTS: Dermatomyositis was the most common subtype (45.5%), with a female predominance (66.1%). Cancer diagnosis occurred in 11.6% of cases, predominantly thyroid cancer. The median time from myopathy onset to cancer diagnosis was 11 months, with 75% of cases within the first year. Bivariate analysis indicated associations between cancer and age, Gottron's papules, digital ulcers, and heliotrope rash. However, multivariate analysis identified age as the only significant malignancy risk factor. Survival analysis showed better rates in younger patients. CONCLUSION: This study provides into the link between IM and cancer in the Colombian population. Thyroid cancer predominated, with a slightly higher proportion of female cancer diagnoses. Age emerged as a significant risk factor for malignancy. Understanding this association is crucial for early detection and improving patient outcomes related to IM-associated malignancies.

Exploring the Therapeutic Potential of Extracellular Vesicles Derived from Human Immature Dental Pulp Cells on Papillary Thyroid Cancer.

Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) have been increasingly investigated for cancer therapy and drug delivery, and they offer an advanced cell-free therapeutic option. However, their overall effects and efficacy depend on various factors, including the MSC source and cargo content. In this study, we isolated EVs from the conditioned medium of human immature dental pulp stem cells (hIDPSC-EVs) and investigated their effects on two papillary thyroid cancer (PTC) cell lines (BCPAP and TPC1). We observed efficient uptake of hIDPSC-EVs by both PTC cell lines, with a notable impact on gene regulation, particularly in the Wnt signaling pathway in BCPAP cells. However, no significant effects on cell proliferation were observed. Conversely, hIDPSC-EVs significantly reduced the invasive capacity of both PTC cell lines after 120 h of treatment. These in vitro findings suggest the therapeutic potential of hIDPSC-EVs in cancer management and emphasize the need for further research to develop novel and effective treatment strategies. Furthermore, the successful internalization of hIDPSC-EVs by PTC cell lines underscores their potential use as nanocarriers for anti-cancer agents.

Two Decades of Thyroid Nodule Cytology in Children: Malignancy Risk Assessment at a Tertiary Care Center.

INTRODUCTION: Pediatric thyroid nodules exhibit higher malignancy rates compared to adults and are associated with increased incidences of metastases and recurrences. The American Thyroid Association recommends surgery for indeterminate thyroid biopsies in children based on these higher malignancy risks, though this approach may lead to overtreatment. However, there remains a lack of comprehensive pediatric data to inform clinical decisions. This study examines the risk of malignancy (ROM) in pediatric thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and assesses the diagnostic accuracy of fine-needle aspiration (FNA) biopsy compared to histological outcomes. METHODS: A retrospective cross-sectional analysis was performed on patients under 19 years with thyroid nodules who underwent FNA and thyroidectomy at a tertiary care center. The sensitivity, specificity, positive predictive value, negative predictive value, and ROM of cytological biopsies were evaluated using TBSRTC criteria, with histology serving as the gold standard. Two analyses were conducted to assess diagnostic accuracy: (a) TBSRTC II as negative and TBSRTC VI as positive and (b) TBSRTC II as negative with TBSRTC V and VI as positive. For neoplasia detection, TBSRTC II was deemed negative, while TBSRTC IV, V, and VI were considered positive. TBSRTC categories III and I were excluded from the performance analysis and evaluated separately. Follicular neoplasm or lesions suspicious for follicular neoplasm (FN/SFN) were treated as positive outcomes, correlated with the presence of adenoma or carcinoma in the surgical specimen. RESULTS: Of 75 nodules from 73 patients, 28 (37.3%) were benign and 47 (62.6%) malignant. No significant differences in gender or age were noted between groups. The ROM in each TBSRTC was Bethesda I 0/2, 0%; II 0/13, 0%; III 2/7, 29%: IV 6/14, 43%; V 10/10, 100%, and VI 29/29, 100%. A sensitivity of 78.38% and specificity of 100% for FNA in detecting malignancy was found, with an even higher sensitivity (100%) for detecting neoplasia in TBSRTC IV. CONCLUSIONS: This study reveals that indeterminate thyroid nodules in pediatric patients exhibit a higher rate of malignancy compared to adults, yet align with rates previously reported in the pediatric population. These findings highlight the critical need for guidelines tailored specifically to the management of thyroid nodules and thyroid cancer in children.

Anaplastic thyroid cancer cell-secreted TGFß1 plays a key role in inducing macrophage polarization of human monocytes.

Anaplastic thyroid cancer (ATC) is a clinically aggressive form of undifferentiated thyroid cancer with limited treatment options. Tumor-associated macrophages (TAMs) constitute over 50% of ATC-infiltrating cells, and their presence is associated with a poor prognosis. We have previously shown that paracrine signals released by ATC cells induced pro-tumor M2-like polarization of human monocytes. However, which soluble factors derived from ATC cells drive monocyte activation, are largely unknown. In this study we investigated the participation of transforming growth factor ß1 (TGFß1) on the phenotype of macrophage activation induced by ATC cell-derived conditioned media (CM). THP-1 cells exposed to CM derived from ATC cells and recombinant human TGFß1 induced M2-like macrophage polarization, showing high CD163 and Dectin1 expression. Moreover, we showed that TGFß1 induced the messenger RNA (mRNA) and protein expression of the transcription factors SNAIL and SLUG. Accordingly, increased TGFß1 secretion from ATC cells was confirmed by enzyme-linked immunosorbent assay (ELISA). Addition of SB431542, a TGFß receptor inhibitor, significantly decreased the Dectin1, CD163, SNAIL and SLUG expression stimulated by ATC cell-derived CM. We validated the clinical significance of the expression of TGFß ligands, their receptors, as well as SNAIL and SLUG in human ATC by analyzing public microarray datasets. We found that the expression of the main TGFß ligands, TGFß1 and TGFß3, along with their receptors, TGFR1 and TGFR2, as well as SLUG, was significantly higher in human ATC tissue samples than in normal thyroid tissues. Our findings indicate that ATC cell-secreted TGFß1 may play a key role in M2-like macrophage polarization of human monocytes and in the up-regulation of SNAIL and SLUG transcription factors. Thus, ours results uncovered a novel mechanism involved in the activation of TAMs by soluble factors released by ATC cells, which suggest potential therapeutic targets for ATC.

Thyroid cancer in patients undergoing thyroidectomy total in the Otorhinolaryngology Department of the Hospital de Clínicas during the period 2018-2022

Introduction: Thyroid cancer, considered one of the most frequent malignant tumors of the endocrine system, accounts for 80%-90% of cases. The most common histological type observed in most studies is papillary cancer. Objective: To determine the frequency of thyroid cancer in patients undergoing total thyroidectomy at the Otorhinolaryngology Department of the Hospital de Clínicas between the period 2018-2022. Methodology: This retrospective study included 260 patients treated during the study period. Data were obtained from the patients' medical records, and sociodemographic and clinical variables related to thyroid cancer were analyzed. Data were analyzed with the SPSS v25 program, using descriptive statistics. Results: The frequency of thyroid cancer was 48.1%. The mean age of the cancer patients was 42.10±13.10 years. A higher frequency was observed in females 34.2%, n=89) and among those aged 25-44 years 20.0%, n=52). The most frequent were papillary (36.9%), follicular (2.7%), medullary (1.5%), and anaplastic (1.2%) types. Discussion: The frequency of thyroid cancer is high; it is more common in women and as age increases.

Introducción: El cáncer de tiroides, considerado uno de los tumores malignos más frecuentes del sistema endocrino, representa entre el 80% y el 90% de los casos. El tipo histológico más común observado en la mayoría de los estudios es el cáncer papilar. Objetivo: Determinar la frecuencia de cáncer de tiroides en pacientes sometidos a tiroidectomía total en la Cátedra y Servicio de Otorrinolaringología del Hospital de Clínicas durante el período 2018-2022. Metodología: se realizó un estudio retrospectivo con un total de 260 pacientes atendidos en el período de estudio. Los datos fueron tomados de las historias clínicas de los pacientes, en el cual se analizan variables sociodemográficas y clínicas relacionadas con el cáncer de tiroides. Los datos se analizaron con el programa SPSS v25, mediante estadística descriptiva. Resultados: La frecuencia del cáncer de tiroides fue del 48.1%. El promedio de edad de los pacientes con cáncer fue de 42.10±13.10 años. se observó una mayor frecuencia en las personas del sexo femenino 34.2% (n=89) y entre quienes tuvieron de 25-44 años 20.0% (n=52). El más frecuente fue el tipo papilar 36.9%, el folicular 2.7%, el medular 1.5% y el anaplásico 1.2%. Discusión: la frecuencia de cáncer de tiroides es alta, es más frecuente en las mujeres y a medida que aumenta la edad.

Intraoperative indocyanine green angiography in preventing hypoparathyroidism after thyroid cancer surgery.

BACKGROUND: The aim of this study was to determine whether the use of indocyanine green angiography to identify devascularized parathyroids during thyroidectomy for thyroid cancer would decrease the rates of postoperative hypoparathyroidism. METHODS: Retrospective study of patients who had undergone total thyroidectomy for treatment of thyroid cancer between March 2021 and March 2023. The indocyanine group included patients with all four parathyroids identified and evaluated by indocyanine green angiography at the end of the procedure. Those with parathyroid glands classified with no vascularization had the glands autotransplanted. A group without indocyanine angiography was used to compare results. RESULTS: The analysis included 100 patients in each group. Indocyanine angiography identified 14.75% of devascularized parathyroids at surgery. The number of parathyroids with a score of 2 (i.e., good vascularization) was not a safe predictor of normal parathyroid hormone levels after surgery. Indeed, 29.2% of the patients with three parathyroids with a score of 2 developed transient hypoparathyroidism. Permanent hypoparathyroidism occurred in 7% of the patients without indocyanine group and in none of the patients in the indocyanine group (p = 0.014). CONCLUSION: Intraoperative angiography with indocyanine green could contribute to reduce the occurrence of permanent hypoparathyroidism in patients undergoing surgical treatment for thyroid cancer.

Challenges in treating radioiodine-refractory thyroid cancer: a global perspective with a focus on developing nations in Latin America.

PURPOSE: This article aims to comprehensively analyze the unique challenges in managing patients with metastatic Differentiated Thyroid Cancer (DTC) that develop radioiodine-refractory disease, especially in developing countries in Latin America. We discuss key contentious aspects of their treatment, such as the optimal timing for initiating systemic therapy, the choice of first-line medications, the appropriate timing for requesting molecular interrogation, and the challenges associated with accessing these drugs and molecular panels. METHODS: To illustrate these challenges and enhance understanding, we present five real clinical cases from the authors' experiences. RESULTS: Patients with Differentiated Thyroid Cancer (DTC) generally have an excellent prognosis, with an overall 10-year survival rate exceeding 97%. However, approximately 5% of DTC patients, especially those with distant metastases, may develop radioiodine-refractory disease, reducing survival rates. Access to medications remains difficult and time-consuming, particularly for patients within the public healthcare system. Urgent discussions on drug pricing involving all stakeholders are imperative. To break free from complacency, stakeholders must prioritize patient well-being by advocating for evidence-based drug pricing, increased participation in clinical trials, and streamlined regulatory processes. CONCLUSION: Beyond the recognized need for prospective randomized clinical trials to determine the optimal first-line drug and the timing of molecular testing, this type of manuscript plays a pivotal role in stimulating discussions and disseminating comprehensive knowledge about the challenges associated with treating and monitoring patients with radioiodine-refractory thyroid carcinoma, especially in developing countries.

The diagnostic and prognostic role of miR-146b-5p in differentiated thyroid carcinomas.

Introduction: Samples classified as indeterminate correspond to 10-20% of cytologies obtained by fine needle biopsy of thyroid nodules, preventing an adequate distinction between benign and malignant lesions and leading to diagnostic thyroidectomies that often prove unnecessary, as most cases are benign. Furthermore, although the vast majority of patients with differentiated thyroid cancer (DTC) have such a good prognosis that active surveillance is permitted as an initial therapeutic option, relapses are not rare, and a non-negligible number of patients experience poor outcomes. MicroRNAs (miR) emerge as potential biomarkers capable of helping to define more precise management of patients in all these situations. Methods: Aiming to investigate the clinical utility of miR-146b-5p in the diagnostic of thyroid nodules and evaluating its prognostic potential in a realworld setting, we studied 89 thyroid nodule samples, correlating miR-146b-5p expression with clinical tools such as the 8th edition from the American Joint Committee on Cancer (AJCC/UICC) and the American Thyroid Association Guideline Stratification Systems for the rate of recurrence (RR). Results: miR-146b-5p expression levels distinguished benign from malignant thyroid FNA samples (p< 0.0001). For indeterminate nodules, overexpression of miR-146b-5p with a cut-off of 0.497 was able to diagnose malignancy with a 90% accuracy; specificity=87.5%; sensitivity=100%. An increased expression of miR-146b-5p was associated with greater RR (p=0.015). A cut-off of 2.21 identified cases with more vascular involvement (p=0.013) and a cut-off of 2.420 was associated with a more advanced TNM stage (p-value=0.047). Discussion: We demonstrated that miR-146b5p expression in FNA samples is able to differentiate benign from malignant indeterminate nodules and is associated with an increased risk of recurrence and mortality, suggesting that this single miRNA may be a useful diagnostic and prognostic marker in the personalized management of DTC patients.

DLK1-DIO3 region as a source of tumor suppressor miRNAs in papillary thyroid carcinoma.

BACKGROUND: In previous studies, we demonstrated the downregulation of several miRNAs from the DLK1-DIO3 genomic region in papillary thyroid carcinoma (PTC). Due to the large number of miRNAs within this region, the individual contribution of these molecules to PTC development and progression remains unclear. OBJECTIVE: In this study, we aimed to clarify the contribution of DLK1-DIO3-derived miRNAs to PTC. METHODS: We used different computational approaches and in vitro resources to assess the biological processes and signaling pathways potentially modulated by these miRNAs. RESULTS: Our analysis suggests that, out of more than 100 mature miRNAs originated from the DLK1-DIO3 region, a set of 12 miRNAs accounts for most of the impact on PTC development and progression, cooperating to modulate distinct cancer-relevant biological processes, such as cell migration, extracellular matrix remodeling, and signal transduction. The restoration of the expression of one of these miRNAs (miR-485-5p) in a BRAFT199A-positive PTC cell line impaired proliferation and migration, suppressing the expression of GAB2 and RAC1, validated miR-485-5p targets. CONCLUSIONS: Overall, our results shed light on the role of the DLK1-DIO3 region, which harbors promising tumor suppressor miRNAs in thyroid cancer, and open prospects for the functional exploration of these miRNAs as therapeutic targets for PTC.

Assessment of inflammatory parameters as predictive markers for malignancy in thyroid nodules: a study on the correlation with Bethesda classification.

OBJECTIVE: The study aimed to assess the predictive significance of inflammatory parameters as potential markers for malignancy in individuals with thyroid nodules. METHOD: Nine hundred and ninety-one patients with thyroid nodules who had undergone thyroid fine-needle aspiration biopsy were included and classified according to the Bethesda system. Neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) values obtained from hemogram parameters were determined for each patient. The study examined the correlation between the Bethesda classification and NLR/SII levels. In addition, a comparison was made between the inflammatory parameters of the benign and malignant Bethesda groups. RESULTS: Five hundred and seventy-three patients were classified as Bethesda 2 (benign), 34 as Bethesda 6 (malignant). A correlation was observed between the Bethesda classification and NLR and SII levels (r: 0.230, p < 0.001; r: 0.207 p < 0.001, respectively). NLR and SII values were significantly higher in the malignant group (p < 0.001). The cutoff value for SII in predicting benign and malignant thyroid nodules was 489.86 × 103/mm3 with a sensitivity of 88.2% and a specificity of 63.7%. The cutoff value for NLR for the same prediction was 2.06 with a sensitivity of 82.4% and a specificity of 83.4%. CONCLUSIONS: The findings of this study indicate that SII and NLR may be valuable prognostic markers for predicting the malignancy of thyroid nodules.

OBJETIVO: Evaluar parámetros inflamatorios como posibles marcadores de malignidad en individuos con nódulos tiroideos. MÉTODO: Se incluyeron 991 pacientes con nódulos tiroideos que se sometieron a biopsia por aspiración con aguja fina y se clasificaron según el sistema de Bethesda. Se determinaron los valores de la relación neutrófilo-linfocito (NLR) y el índice de inflamación inmunitaria sistémica (SII). El estudio exploró la correlación entre la clasificación de Bethesda y los valores de NLR/SII, y comparó los parámetros inflamatorios de los grupos benignos y malignos de Bethesda. RESULTADOS: Se clasificaron 573 pacientes como Bethesda 2 (benigno) y 34 como Bethesda 6 (maligno). Se observó una correlación entre la clasificación de Bethesda y los valores de NLR y SII (r: 0.230; r: 0.207). Los valores de NLR y SII fueron mayores en el grupo maligno (p < 0.001). El valor de corte para SII en la predicción de nódulos tiroideos benignos y malignos fue de 489.86 × 103/mm3, con una sensibilidad del 88.2% y una especificidad del 63.7%; para NLR fue de 2.06, con una sensibilidad del 82.4% y una especificidad del 83.4%. CONCLUSIONES: El SII y el NLR pueden ser valiosos marcadores pronósticos para predecir la malignidad de los nódulos tiroideos.

Biomarkers in Thyroid Cancer: Emerging Opportunities from Non-Coding RNAs and Mitochondrial Space.

Thyroid cancer diagnosis primarily relies on imaging techniques and cytological analyses. In cases where the diagnosis is uncertain, the quantification of molecular markers has been incorporated after cytological examination. This approach helps physicians to make surgical decisions, estimate cancer aggressiveness, and monitor the response to treatments. Despite the availability of commercial molecular tests, their widespread use has been hindered in our experience due to cost constraints and variability between them. Thus, numerous groups are currently evaluating new molecular markers that ultimately will lead to improved diagnostic certainty, as well as better classification of prognosis and recurrence. In this review, we start reviewing the current preoperative testing methodologies, followed by a comprehensive review of emerging molecular markers. We focus on micro RNAs, long non-coding RNAs, and mitochondrial (mt) signatures, including mtDNA genes and circulating cell-free mtDNA. We envision that a robust set of molecular markers will complement the national and international clinical guides for proper assessment of the disease.

Lobectomy in patients with differentiated thyroid cancer: experience of a Chilean tertiary center.

PURPOSE: Thyroid lobectomy (TL) is an appropriate treatment for up to 4 cm intrathyroidal differentiated thyroid cancer (DTC). There is scarce data regarding TL outside first-world centers. Our aim is to report a cohort of patients with DTC treated with TL in Chile. METHODS: We included DTC patients treated with TL, followed for at least 6 months, characterized their clinicopathological features and classified their risk of recurrence and response to treatment. RESULTS: Eighty-two patients followed for a median of 2.3 years (0.5-7.0). Seventy-three (89%) patients had papillary, 8 (9.8%) follicular and 1 (1.2%) high-grade DTC. The risk of recurrence was low in 56 (68.3%) and intermediate in 26 (31.7%). Eight (9.8%) patients required early completion thyroidectomy and radioiodine. At last follow-up, 52 (70.3%) had excellent, 19 (25.7%) had indeterminate, and 1 (1.4%) had structural incomplete response. CONCLUSION: In a developing country, TL is an adequate option for appropriately selected DTC patients.

Efficacy and safety of BRAF/MEK inhibitors in BRAFV600E-mutated anaplastic thyroid cancer: a systematic review and meta-analysis.

PURPOSE: Approximately 45% of anaplastic thyroid cancer (ATC) patients harbor a BRAFV600E mutation and are eligible for target therapy (TT) with BRAF and MEK inhibitors (BRAFi/MEKi), nevertheless, few data advocate for this. Hence, we've conducted a systematic review and meta-analysis investigating the effectiveness and safety of BRAFi/MEKi in BRAFV600E ATC patients. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for BRAFi/MEKi TT in BRAFV600E ATC patients. Outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), duration of response (DOR) and adverse events (AEs). RESULTS: Nine studies with 168 patients were included. Median follow-up ranged from 2.0 to 47.9 months. 75% of patients had stage IVc. In a pooled analysis, ORR was 68.15% (95% CI 55.31-80.99, I2 = 47%) and DCR was 85.39% (95% CI 78.10-92.68, I2 = 0), with a median DOR of 14.4 months (95% CI 4.6-14.4) and a median PFS of 6.7 months (95% CI 4.7-34.2). Moreover, 1-year OS rate was 64.97% (95% CI 48.76-81.17, I2 = 84%) and 2-years OS rate was 52.08% (95% CI 35.71-68.45, I2 = 79%). Subgroup analysis showed patients in the neoadjuvant setting had higher rates of 1 and 2-years OS and observational studies tended to report higher rates of ORR than clinical trials. No new or unexpected adverse events were found. CONCLUSIONS: Our study demonstrated BRAFi/MEKi have a decent activity for BRAFV600E ATC patients, especially in the neoadjuvant setting, with a tolerable safety profile. However, further clinical trials are warranted to investigate these findings.

Active surveillance of nodal metastasis in differentiated thyroid carcinoma: a systematic review and meta-analysis.

PURPOSE: Cervical lymph nodes (LN) represent the most common site of recurrence in differentiated thyroid cancer (DTC), frequently requiring repeated interventions that contribute to increase morbidity to a usually indolent disease. Data on active surveillance (AS) of nodal metastasis are limited. Therefore, we performed a systematic review and meta-analysis to evaluate AS in nodal metastasis of DTC patients. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched up to July 2023 for studies including DTC patients with metastatic LN who were followed up with AS. The primary outcome was disease progression, according to the study's definition. Additional outcomes were LN enlargement ≥3 mm, occurrence of new cervical metastasis, and conversion from AS to surgical treatment. RESULTS: The search identified 375 studies and seven were included, comprising 486 patients with metastatic nodal DTC. Most were female (69.5%) and had papillary thyroid cancer (99.8%). The mean AS follow-up ranged from 28-86 months. Following each study's definition of progression, the pooled incidence was 28% [95% confidence interval (CI), 20-37%]. The pooled incidence of LN growth ≥ 3 mm was 21% [95% CI, 17-25%] and the emergence of new LN sites was 19% [95% CI, 14-25%]. Combining growth of 3 mm and the emergence of new LN criteria, we found an incidence of 26% [95% CI, 20-33%]. The incidence of neck dissection during AS was 18% [95% CI, 12-26%]. CONCLUSIONS: AS seems to be a suitable strategy for selected DTC patients with small nodal disease, avoiding or postponing surgical reintervention. PROSPERO REGISTRATION: CRD42023438293.

Community-acquired pneumonia associated with immunosuppression due to follicular thyroid cancer: a case report.

BACKGROUND: We present the case of a woman with cancer, which weakened the immune system and increased the risk of infection. Thus, infections are a frequent complication of cancer. The development of community-acquired pneumonia, an acute respiratory infectious disease that damages the lung parenchyma, caused by the invasion of pathogenic microorganisms, can lead to respiratory failure with multiorgan failure due to respiratory sepsis. CASE PRESENTATION: Case report of a 38-year-old mixed-race woman with diabetes mellitus and irregular treatment, who was admitted with community-acquired pneumonia complicated by type I respiratory failure requiring mechanical ventilation. During her hospital stay, she developed ventilator-associated pneumonia, recurrent empyema, bronchopleural fistula, refractory septic shock and multiorgan dysfunction despite multiple interventions. The patient required prolonged mechanical ventilation, vasopressor support and antibiotic therapy. After 62 days, metastatic papillary thyroid carcinoma was diagnosed. She presented with hypoparathyroidism and permanent hypocalcemia. She died after multiple complications and a refractory critical condition. CONCLUSION: The case exemplifies the potential severity of community-acquired pneumonia in a patient with risk factors such as diabetes and immunosuppression. It highlights the complexity of treating multiple comorbidities and the importance of multidisciplinary management with close surveillance for timely interventions for complications.

Ten years' real-life experience on the use of multikinase inhibitors in patients with advanced differentiated thyroid cancer.

PURPOSE: To evaluate objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) associated with tyrosine kinase inhibitors (TKIs) in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC). Additionally, to compare: (i) ORR and PFS among patients treated with lenvatinib and sorafenib; (ii) ORR and PFS among patients receiving lenvatinib as first-line vs. second-line and; (iii) adverse effects (AEs) observed in patients treated with these medications. METHODS: Retrospective analysis of RR-DTC adult patients treated with TKIs at the Division of Endocrinology, Hospital de Clinicas, University of Buenos Aires (March 2011-November 2023). RESULTS: Among 43 patients included in the study, 32 received sorafenib (30 as first-line and 2 as second-line), while 29 received lenvatinib (12 as first-line and 17 as second-line). The median PFS and OS for the entire cohort were 32.7 and 39.0 months, respectively. Lenvatinib demonstrated a significantly higher ORR compared to sorafenib (37.9% vs. 9.4%, p = 0.008). However, both drugs exhibited similar median PFS (23.2 vs. 16.0 months, p = 0.419). No significant difference was observed in ORR and PFS between patients receiving first-line vs. second-line lenvatinib. Sorafenib-treated patients experienced higher rates of hand-foot skin syndrome (69% vs. 41%, p = 0.032) and alopecia (25% vs. 3%, p = 0.018), whereas lenvatinib-treated patients had higher rates of proteinuria (31% vs. 0%, p < 0.001) and grade 3 hypertension (31% vs. 9%, p = 0.034). CONCLUSION: TKIs demonstrated efficacy and tolerability comparable to real-world data in RR-DTC. PFS was not statistically different between sorafenib and lenvatinib. Our study will help guide physicians in making informed decisions regarding treatment sequencing with TKIs in these patients.