Optimizing Diagnostic Accuracy of Fine Needle Aspiration Biopsy Calcitonin Measurements in Detecting Medullary Thyroid Carcinoma.

Background: The optimal cutoff value of calcitonin (Ctn) levels measured using an electrochemiluminescence immunoassay (ECLIA) obtained from the washout fluid of fine needle aspiration (FNA-Ctn) for the diagnosis of medullary thyroid carcinoma (MTC) is currently not established. We evaluated the diagnostic accuracy and clinical utility of FNA-Ctn for the diagnosis and location of MTC in patients with nodular or multinodular goiters. Methods: This was a case-control study nested on a prospective multicenter cohort of patients with nodular or multinodular goiter, normal or elevated serum Ctn, and thyroidectomy indications. Ctn and FNA-Ctn were measured using ECLIA methodology before surgery. From this nested cohort, MTC cases and controls (non-medullary pathology) were identified from the final pathological analysis. Cumulative incidence sampling of controls was randomly performed at a ratio of 1:2. Sensitivity, specificity, and area under the receiver operator curve (AUROC) were calculated for patients and the total number of thyroid nodules. Results: From 1272 patients included in the prospective cohort, 50 MTC cases and 105 controls were included. In this study, 286 thyroid nodules were evaluated (63 MTC and 223 non-MTCs). The median serum Ctn value was significantly higher in cases (525 pg/mL [interquartile range (IQR), 162.5-1.200]) than in controls (1.6 pg/mL [IQR, 0.5-5.6]; p < 0.001). The median FNA-Ctn value was significantly higher in MTC nodules (3.100 pg/mL [IQR, 450-45,200]) than in non-MTC nodules (0.5 pg/mL [IQR, 0.5-0.5]; p < 0.0001). In 11 MTC patients with multinodular goiter, the FNA-Ctn value was significantly higher in non-medullary nodules located in the same lobe where an MTC nodule was diagnosed (p = 0.0002). Overall, the FNA-Ctn AUROC was 0.99 [95% confidence interval, 0.98-1.0], and a threshold of ≥220 pg/mL showed 100% sensitivity and 98% specificity for MTC diagnosis. Conclusions: The use of FNA-Ctn measured by ECLIA showed adequate diagnostic accuracy for MTC diagnosis. Moreover, it may be clinically useful for localization in multinodular goiter when lobectomy is considered. Clinical Trial Registration: Clinicaltrials.gov NCT06067594.

Dabrafenib plus trametinib treatment in patients with anaplastic thyroid carcinoma: an Argentinian experience.

PURPOSE: To present our real-life experience with dabrafenib and trametinib (D-T) treatment in patients with BRAF V600E-mutated ATC in Argentina. PATIENTS Y METHODS: We included five patients from four different hospitals. The median age was 70 years, and 60% were male. The performance status at diagnosis was grade 0 in 60% and grade 2 in 40% of patients. Four patients could undergo total thyroidectomy; in one of them, surgical treatment was amenable due to the indication of D-T as neoadjuvant therapy. From the total cohort, the best response to treatment was complete response in 40%, partial response in 20%, and stable disease in 20%. The median duration of response was 20 weeks, ranging from 16 to 92 weeks. All patients experienced at least one adverse event (AE). Grade ≥3 AEs were observed in two (40%) patients. They were upper gastrointestinal bleeding and subclavian vein thrombosis. The median follow-up was 20 weeks (range: 16 to 92). CONCLUSION: This report contributes to illustrate the feasibility and effectiveness of D-T treatment in five patients with loco-regionally advanced and metastatic BRAF V600E-mutated ATC in a real-life setting. A multidisciplinary approach and rapid molecular-tailored testing are essential to begin this therapeutic option.

Autophagy Dysregulation in Diabetic Kidney Disease: From Pathophysiology to Pharmacological Interventions.

Diabetic kidney disease (DKD) is a frequent, potentially devastating complication of diabetes mellitus. Several factors are involved in its pathophysiology. At a cellular level, diabetic kidney disease is associated with many structural and functional alterations. Autophagy is a cellular mechanism that transports intracytoplasmic components to lysosomes to preserve cellular function and homeostasis. Autophagy integrity is essential for cell homeostasis, its alteration can drive to cell damage or death. Diabetic kidney disease is associated with profound autophagy dysregulation. Autophagy rate and flux alterations were described in several models of diabetic kidney disease. Some of them are closely linked with disease progression and severity. Some antidiabetic agents have shown significant effects on autophagy. A few of them have also demonstrated to modify disease progression and improved outcomes in affected patients. Other drugs also target autophagy and are being explored for clinical use in patients with diabetic kidney disease. The modulation of autophagy could be relevant for the pharmacological treatment and prevention of this disease in the future. Therefore, this is an evolving area that requires further experimental and clinical research. Here we discuss the relationship between autophagy and Diabetic kidney disease and the potential value of autophagy modulation as a target for pharmacological intervention.

El cáncer diferenciado de tiroides: experiencia clínica frente a un panorama cambiante / Differentiated thyroid cancer: clinical experience in a changing scenario

Antecedentes: el cáncer de tiroides es el cáncer endocrino más frecuente, ha aumentado significativamente su incidencia y se han producido importantes cambios en su tratamiento. Objetivos: analizar una población de pacientes con cáncer diferenciado de tiroides tratados en el Hospital Universitario Austral, evaluar sus resultados y discutir las nuevas tendencias en su manejo. Material y métodos: revisión retrospectiva de una serie de 344 pacientes operados entre mayo de 2001 y mayo de 2015; se realizaron 331 tiroidectomías totales y 13 lobectomías, con linfadenectomía central en el 82% y lateral en el 9 %, según hallazgos clínicos o ultrasonográficos. El 80% correspondieron al sexo femenino y el 95% fueron carcinomas papilares. De acuerdo con TNM, el 65 % fueron T1, 41% T1a (microcarcinomas) y, según ATA, el 87 % tenían bajo riesgo de recurrencia. El 34 % de los vaciamientos centrales y todos los laterales presentaron metástasis ganglionares, y solo el 1,8% presentó metástasis a distancia. El 73% de los pacientes recibieron I131 en dosis de 30 a 150 mCi (milicurios). Resultados: la supervivencia global fue del 99,2% con seguimiento promedio de 40,2 meses, con 0,8% de hipoparatiroidismo definitivo y 0,8% de parálisis recurrencial definitiva. Conclusiones: 1) casi el 80% de la población operada correspondía a estadios tempranos con bajo riesgo de recurrencia, 2) más del 40% correspondió a microcarcinomas, 3) los resultados obtenidos son similares a los comunicados por centros de alto volumen, 4) las conductas terapéuticas coincidieron con las recomendaciones de las guías en vigencia y con las nuevas tendencias en el manejo del cáncer diferenciado de tiroides.

Background: Thyroid cancer is the most common type of endocrine cancer with an incidence that is significantly increasing and with important treatment changes. Objectives: The aim of this study was to analyze a population of patients with differentiated thyroid cancer treated at the Hospital Universitario Austral, evaluate the outcomes and discuss the new trends in thyroid cancer management. Material and methods: A series of 344 patients undergoing thyroid surgery between May 2001 and May 2015 were retrospectively reviewed: 331 total thyroidectomies and 13 lobectomies. Central lymph node dissection was performed in 82% of the cases and lateral lymph node dissection in 9%, based on clinical and ultrasound findings. Most patients were women (80%) and 95% were papillary thyroid cancers. According to the TNM classification, 65% were T1, 41% T1a (microcarcinomas) and 87% corresponded to the ATA low risk of recurrence category. Lymph node metastases were present in 34% of the central neck lymph nodes and in all the lateral lymph nodes dissected, and only 1.8% presented distant metastasis. Radioactive iodine was used in 73% of the patients in doses between 30 and 150 mCi. Results: Overall survival was 99.2% with a mean follow-up of 40.2 months; 0.8% presented permanent hypoparathyroidism and 0.8% of the patients presented permanent recurrent laryngeal nerve palsy. Conclusions: 1) almost 80% of the patients undergoing surgery corresponded to early stages of the disease with low risk of recurrence; 2) more than 40% were microcarcinomas; 3) the results obtained are similar to those reported by high-volume centers; and 4) the review of this experience is similar to that reported by current practice guidelines, and the therapeutic approaches are in line with the recommendations of the current practice guidelines and with the new trends in the management of differentiated thyroid cancer.