RESUMO
CONTEXT: The utility of thyroglobulin (Tg) in the follow-up of differentiated thyroid cancer (DTC) patients has been well-documented. Although third-generation immunoassays have improved accuracy, limitations persist (interfering anti-Tg antibodies and measurement variability). Evolving treatment strategies require a reevaluation of Tg thresholds for optimal patient management. OBJECTIVE: To assess the performance of serum Tg testing in two populations: patients receiving total thyroidectomy and radioiodine remnant ablation (RRA), or treated with thyroidectomy alone. DESIGN: Prospective observational study. Setting. Centers contributing to the Italian Thyroid Cancer Observatory (ITCO) database. PATIENTS: We included 540 patients with 5 years of follow-up and negative anti-Tg antibodies. INTERVENTIONS: Serum Tg levels assessed at 1-year follow-up visit. MAIN OUTCOME MEASURE: Detection of structural disease within 5 years of follow-up. RESULTS: After excluding 26 patients with structural disease detected at any time point, the median Tg did not differ between patients treated with or without radioiodine. Data-driven Tg thresholds were established based on the 97th percentile of Tg levels in disease-free individuals: 1.97 ng/mL for patients undergoing thyroidectomy alone (lower than proposed by the MSKCC protocol and ESMO Guidelines, yet demonstrating good predictive ability, with a negative predictive value (NPV) of 98%) and 0.84 ng/mL for patients receiving post-surgical RRA. High sensitivity and NPV supported the potential of these thresholds in excluding structural disease. CONCLUSIONS: This real-world study provides evidence for the continued reliability of 1-year serum Tg levels. The data-driven Tg thresholds proposed offer valuable insights for clinical decision-making in patients undergoing total thyroidectomy with or without RRA.
RESUMO
Background: Tyrosine kinase inhibitors (TKIs) and immunotherapy have been proposed for advanced metastatic anaplastic thyroid cancer (ATC). We report a case of BRAF V600E-mutated ATC in which lenvatinib (L) plus pembrolizumab (P) enabled neoadjuvant treatment. Case presentation: A male patient aged 65 years presented with a rapidly enlarging left latero-cervical mass. Fine needle aspiration was suggestive of ATC. Surgical consultation excluded radical surgery. While awaiting molecular profile analysis and considering the fast evolution of the disease, treatment with L and P was started. L was started at a dose of 14 mg daily, while P was started at the standard regimen (200 mg every 3 weeks). After 1 month, computerized tomography showed a reduction in the mass with almost complete colliquative degeneration, and the carotid artery wall was free from infiltration. Radical surgery was performed. Histology confirmed papillary thyroid cancer (PTC) in the left lobe and ATC with extensive necrosis in the left latero-cervical lymph node metastasis. The margins were free of tumors (R0). A BRAF V600E mutation was present in both PTC and ATC. At the 1-year follow-up, the patient was free of disease. Conclusion: L and P in combination also appeared to be effective as a neoadjuvant treatment for BRAF V600E-mutated ATC. This combination treatment could be used when there is an opportunity for complete resection of the cancer, and as soon as possible. The intermediate dose of 14 mg of L appeared to be well tolerated and effective.
Assuntos
Anticorpos Monoclonais Humanizados , Terapia Neoadjuvante , Compostos de Fenilureia , Proteínas Proto-Oncogênicas B-raf , Quinolinas , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Masculino , Proteínas Proto-Oncogênicas B-raf/genética , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/patologia , Quinolinas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Idoso , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Mutação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND:
Assuntos
Inositol , Obesidade , Síndrome do Ovário Policístico , Inositol/uso terapêutico , Humanos , Feminino , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Resistência à Insulina/fisiologiaRESUMO
BACKGROUND: Osteoporosis is a common concern in the elderly that leads to fragile bones. Calcium supplementation plays a crucial role in improving bone health, reducing fracture risk, and supporting overall skeletal strength in this vulnerable population. However, there is conflicting evidence on the safety of calcium supplements in elderly individuals. AIM: The aim of this study was to evaluate the adherence, safety and tolerability of calcium citrate supplementation in elderly osteopenic subjects. METHODS: In this non-interventional, prospective, multicenter study, subjects received daily 500 mg calcium citrate supplementation for up to one year. Adherence was calculated based on compliance and persistence. Safety was assessed through adverse reactions (ARs), deaths, and clinical laboratory evaluations. RESULTS: A total of 268 Caucasian subjects (91.4% female, mean age 70 ± 4.5 years) participated in the study. Mean adherence to treatment was 76.6 ± 29.5% and half of subjects had an adherence of 91% and ~ 33% of participants achieved complete (100%) adherence. ARs were reported by nine (3.9%) subjects, primarily gastrointestinal disorders, with no serious ARs. The frequency of all adverse events (including ARs) was significantly higher in subjects with adherence of < 80% (41.6%; 32/77) vs. those with adherence ≥ 80% (11%; 16/145, p < 0.0001). Both systolic and diastolic blood pressure decreased from baseline to follow-up visit (change of -2.8 ± 13.9 mmHg, p = 0.0102 and -2.1 ± 10.4 mmHg, p = 0.0116, respectively). CONCLUSION: This study demonstrated favorable adherence to calcium citrate supplementation in elderly osteopenic subjects. The occurrence of ARs, though generally mild, were associated with lower adherence to calcium supplementation.
Assuntos
Citrato de Cálcio , Osteoporose , Humanos , Feminino , Idoso , Masculino , Citrato de Cálcio/efeitos adversos , Cálcio , Estudos Prospectivos , Osteoporose/tratamento farmacológico , Cálcio da Dieta , Suplementos Nutricionais/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: False-positive radioiodine uptake can sometimes be observed with post-radioiodine treatment (RIT) whole body scanning. Radioiodine pitfall has often been reported as being caused by benign or inflammatory disease, or, in some cases, by tumor lesions. This paper reviews the possible causes of such false-positive imaging, and suggests possible reasons for suspecting these pitfalls. METHODS AND RESULTS: Online databases, including MEDLINE (via PubMed), Embase, ISI Web of Science, Google Scholar, and Scopus, were systematically examined, using different keyword combinations: "radioiodine false-positive imaging", "131 I false-positive imaging" and " RAI false-positive imaging". An illustrative case was described. Excluding cases in which SPECT/CT was not performed, a total of 18 papers was found: 17 case reports and one series regarding false-positive iodine-131 uptake after RIT. CONCLUSIONS: The prevalence of radioiodine pitfall was significantly reduced through the use of SPECT/CT imaging, though its possible presence has always to be taken into account. Inflammation, passive iodine accumulation, other tumors, and, sometimes, unknown causes can all potentially generate false-positive imaging. Missing detection of false-positive imaging could result in over-staging and inappropriate RIT or it could lead to the non-detection of other cancers. We examine the reasons for these possible pitfalls.
Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/patologia , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Imagem Corporal TotalRESUMO
Superparamagnetic iron oxide nanoparticles (SPIONs) coated with glucose (Glc-SPIONs) were prepared by a new approach called Metal Vapor Synthesis (MVS) and their morphological/structural features were investigated by transmission electron microscopy (TEM) and dynamic light scattering. TEM analysis revealed the presence of small roundish crystalline iron oxide nanoparticles in the organic amorphous phase of glucose, The particles were distributed in a narrow range (1.5 nm-3.5 nm) with a mean diameter of 2.7 nm. The hydrodynamic mean diameter of the Glc-SPIONs, was 15.5 nm. From 4 mg/mL onwards, there was a constant level of positive contrast in a T1-weighted sequence. In vitro experiments were performed in three cell lines: pancreatic cancer (PSN-1), human thyroid cancer (BCPAP), and human embryonic kidney non-tumor cells. We evaluated GLUT1 expression in each cell line and demonstrated that the exposure time and concentration of the Glc-SPIONs we used did not affect cell viability. PSN-1 cells were the most effective at internalizing Glc-SPIONs. Although significantly higher than the control cells, a lower Fe content was detected BCPAP cells treated with Glc-SPIONs. To confirm the involvement of GLUT1 in Glc-SPIONs internalization, cellular uptake experiments were also conducted by pre-treating cancer cells with specific GLUT1 inhibitors, All the inhibitors reduced the cancer cell uptake of Glc-SPIONs In vivo tests were performed on mice inoculated with Lewis lung carcinoma. Mice were treated with a single i.v. injection of Glc-SPION and our results showed a great bioavailability to the malignant tissue by the i.v. administration of Glc-SPIONs. Glc-SPIONs were efficiently eliminated by the kidney. To the best of our knowledge, our study demonstrates for the first time that Glc-SPIONs prepared with MVS can be electively internalized by tumor cells both in vitro and in vivo by exploiting one of the most universal metabolic anomalies of cancer.
Assuntos
Nanopartículas de Magnetita , Neoplasias , Animais , Compostos Férricos/química , Glucose , Transportador de Glucose Tipo 1 , Técnicas In Vitro , Nanopartículas Magnéticas de Óxido de Ferro , Nanopartículas de Magnetita/química , Camundongos , Neoplasias/terapiaRESUMO
OBJECTIVES: To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years. METHODS: Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered. RESULTS: A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p < 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small (< 10 mL) (74%), medium (49%), or large (> 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment. CONCLUSIONS: Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN. KEY POINTS: ⢠Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). ⢠TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). ⢠Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.
Assuntos
Hipertermia Induzida , Nódulo da Glândula Tireoide , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Resultado do TratamentoRESUMO
Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.
Assuntos
Diabetes Gestacional/tratamento farmacológico , Inositol/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Testosterona/metabolismo , Células Tecais/efeitos dos fármacos , Diabetes Gestacional/metabolismo , Feminino , Humanos , Inositol/química , Inositol/metabolismo , Estrutura Molecular , Síndrome do Ovário Policístico/metabolismo , Gravidez , Transdução de Sinais/efeitos dos fármacos , Células Tecais/metabolismoRESUMO
OBJECTIVE: To analyze all the most recent guidelines/consensus as well as papers regarding the relationship between size of tumor, type of surgery, and prognosis, and to try to produce a critical synthesis for real practice. BACKGROUND: Differentiated thyroid cancer (DTC) is characterized by a wide range of biological behavior. The type of intervention can range from lobectomy (LT) to total thyroidectomy (TT), with tumor size being a point of discussion in choosing the treatment. METHODS: We carried out a search on PubMed, EMBASE, and Cochrane Library, looking at all the guidelines and consensus regarding DTC, as well as examining original articles, inserting as our research keys "total thyroidectomy vs. lobectomy in differentiated thyroid cancer" and "hemithyroidectomy in thyroid cancer". The guidelines and consensus published over the last 5 years were 6 in total: ATA Guidelines, Italian Consensus of Six Italian Societies, United Kingdom National Multidisciplinary Guidelines, ESMO Clinical Practice Guidelines, a Practical Guidance of a Multidisciplinary Panel of Experts, and The Revised Clinical Practise Guidelines on the Management of Thyroid Tumours by the Japanese Association of Endocrine Surgeons. There were 13 papers cited in the guidelines, and we found another 5 original articles, all of which were retrospective studies. CONCLUSIONS: The type of initial surgical intervention must of course consider tumor size, but must also take into account all the risk factors, which is paramount in deciding the type of treatment. LT can have some advantages, and can represent an option that can be offered to patients. However, even in the absence of any special risk factors, a review of the literature suggests to us that patients should be informed that LT for tumors of a size between 2 and 4 cm can be associated with an increased risk of LR as well as with a possible reduced OS.
RESUMO
We report two cases of anaplastic thyroid cancer (ATC) which had a very good response to a treatment with lenvatinib at 14 mg. A 73-year-old man with ATC stage IVB was operated on, undergoing a near-total thyroidectomy, and the pathological remnant tissue showed a quick and partial response to treatment with the drug. The patient had a single metastasis in the brain after 9 months, but then died due to bronchopneumonia after undergoing a neurosurgical intervention for the complete removal of the lesion. A 74-year-old woman with ATC stage IV was operated on, undergoing a near-total thyroidectomy after a neoadjuvant treatment with the drug, that was continued after surgical treatment. She had a partial remission of the local disease and of distant metastasis, which lasted for 14 months. She then died 4 months later due to cancer progression. Lenvatinib at 14 mg appears to be effective, fast and well tolerated.
Assuntos
Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Quinolinas/administração & dosagem , Carcinoma Anaplásico da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Idoso , Quimioterapia Adjuvante/métodos , Relação Dose-Resposta a Droga , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Carcinoma Anaplásico da Tireoide/diagnóstico , Carcinoma Anaplásico da Tireoide/patologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Outcomes of high-intensity focused ultrasound (HIFU), as a non-surgical treatment option for benign symptomatic thyroid nodules, has mainly been based on single-center studies and short-term follow-up. Therefore, we assessed the safety, and long-term efficacy of HIFU in benign thyroid nodules among four centers with expertise in thyroid mini-invasive procedures. PATIENTS AND METHODS: Retrospective three year follow-up study in four European centers, treating solid benign thyroid nodules causing pressure symptoms and/or cosmetic concerns. Nodule volume reduction was assessed at 1, 3, 6, 12, 24, and 36 months post-treatment. Technical efficacy, defined as a volume reduction rate (VVR) >50% was evaluated at 6, 12, 24 and 36 months. Predictive factors of efficacy were assessed using logistic models. Complications and side effects were classified according to the Interventional Radiology Guidelines and changes in local symptoms were scored on a visual-analog scale. RESULTS: Sixty-five patients (mean age 51.1 ± 14.0 years; 86.2% women) with a single thyroid nodule and a mean baseline nodule volume of 9.8 ± 10.3 mL were treated with a mean energy of 7.1 ± 3.1 kJ (range: 2.0 to 15.5 kJ). Median nodule volume reduction was 31.5% (IQR: -38.6% to -23.1%) at 12 months and 31.9% (IQR: -36.4% to -16.1%) at 36 months. Technical efficacy was obtained in 17.2% of cases at 6 months, 17.8% at 12 months, 3.4% at 24 months, and 7.4% at 36 months. The number of treated pixels and the mean energy delivered were positively correlated to VRR at 1, 6 and 12 months. The risk of treatment failure decreased by 4.3% for each additional unit of energy delivered. The procedure duration was inversely correlated with treatment failure (OR 1.043, 95% CI: 1.011-1.083; p = 0.014). Improvement of cervical pressure symptoms or cosmetic complaints were observed in less than 15% of the cases at 12, 24 and 36 months. Horner's syndrome occurred in one case (1.5%) and minor complications, not requiring treatment, in three (4.6%) patients. No change in thyroid function was registered. CONCLUSIONS: HIFU carried a low risk of complications. A single treatment resulted in a 30-35% thyroid nodule volume decrease within one year, reduction that remained stable for 2 years. Outcomes varied significantly between centers with different HIFU expertise. Focus on improved HIFU technology, adequate training, and appropriate selection of patients is needed to achieve efficacy comparable to other thermal ablation procedures.
Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Nódulo da Glândula Tireoide , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: The standard of care for differentiated thyroid carcinoma (DTC) includes surgery, risk-adapted postoperative radioiodine therapy (RaIT), individualized thyroid hormone therapy, and follow-up for detection of patients with persistent or recurrent disease. In 2019, the nine Martinique Principles for managing thyroid cancer were developed by the American Thyroid Association, European Association of Nuclear Medicine, Society of Nuclear Medicine and Molecular Imaging, and European Thyroid Association. In this review, we present our clinical practice recommendations with regard to implementing these principles in the diagnosis, treatment, and long-term follow-up of patients with DTC. METHODS: A multidisciplinary panel of five thyroid cancer experts addressed the implementation of the Martinique Principles in routine clinical practice based on clinical experience and evidence from the literature. RESULTS: We provide a suggested approach for the assessment and diagnosis of DTC in routine clinical practice, including the use of neck ultrasound, measurement of serum thyroid-stimulating hormone and calcitonin, fine-needle aspiration, cytology, and molecular imaging. Recommendations for the use of surgery (lobectomy vs. total thyroidectomy) and postoperative RaIT are also provided. Long-term follow-up with neck ultrasound and measurement of serum anti-thyroglobulin antibody and basal/stimulated thyroglobulin is standard, with 123/131I radioiodine diagnostic whole-body scans and 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography suggested in selected patients. Management of metastatic DTC should involve a multidisciplinary team. CONCLUSIONS: In routine clinical practice, the Martinique Principles should be implemented in order to optimize clinical management/outcomes of patients with DTC.
Assuntos
Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Tireoglobulina , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/terapia , TireoidectomiaRESUMO
Despite universal salt iodization programmes implemented over the last decades, iodine deficiency remains a major public health problem in many countries worldwide. Endeavors are still required to ensure sufficient iodine intake in the populations at risk in order to eliminate deficiency. Iodine is crucial for the synthesis of thyroid hormones triiodothyronine (T3) and thyroxine (T4), as well as for the thyroid health. When iodine levels are insufficient, T4 attests toward the lower limit of the physiological range, causing subtle fluctuations in the T3:T4 ratio. Monitoring these variations may be an accurate way to assess patient's iodine status. Recently, a number of published clinical studies documented a growing interest toward the use of myo-inositol in thyroid diseases. Myo-inositol, a carbocyclic polyol, regulates the generation of hydrogen peroxide (H2O2) in thyrocytes, crucial for iodine organification and thyroid hormone biosynthesis. Thus, combined supplementation of iodine and myo-inositol may promote higher iodine availability in thyrocytes improving thyroid functionality. This review presents novel strategies for the diagnosis and the management of iodine deficiency, focusing on the potential role of myo-inositol combined with iodine.
RESUMO
Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).
Assuntos
Nódulo da Glândula Tireoide/cirurgia , Consenso , Feminino , Humanos , Itália , Masculino , Nódulo da Glândula Tireoide/patologiaRESUMO
OBJECTIVES: The goal of evidence-based practice guidelines is to optimize the management of emerging diseases, such as differentiated thyroid cancer (DTC). The aim of this study was to assess therapeutic approaches for DTC in Italy and to see how closely these practices conformed to those recommended in the 2009 American Thyroid Association (ATA) guidelines. METHODS: The Italian Thyroid Cancer Observatory was established to collect data prospectively on thyroid cancers consecutively diagnosed in participating centers (uniformly distributed across the nation). Data on the initial treatment of all pathologically confirmed DTC cases present in the database from January 1, 2013 (database creation) to January 31, 2016, were analyzed. RESULTS: A total of 1748 patients (77.2% females; median age 48.1 years [range 10-85 years]) were enrolled in the study. Most (n = 1640; 93.8%) were papillary carcinomas (including 84 poorly differentiated/aggressive variants); 6.2% (n = 108) were follicular and Hürthle cell carcinomas. The median tumor diameter was 11 mm (range 1-93 mm). Tumors were multifocal in 613 (35%) and presented extrathyroidal extension in 492 (28%) cases. Initial treatments included total thyroidectomy (involving one or two procedures; n = 726; 98.8%) and lobectomy (n = 22; 1.2%). A quarter of the patients who underwent total thyroidectomy had unifocal, intrathyroidal tumors ≤1 cm (n = 408; 23.6%). Neck dissection was performed in 40.4% of the patients (29.5% had central compartment dissection). Radioiodine remnant ablation (RRA) was performed in 1057 (61.2%) of the 1726 patients who underwent total thyroidectomy: 460 (41.2%) of the 983 classified by 2009 ATA guideline criteria as low-risk, 570 (87.1%) of the 655 as intermediate-risk, and 82 (93.1%) of the 88 as high-risk patients (p < 0.001). RRA was performed in 44% of the cases involving multifocal DTCs measuring ≤1 cm. CONCLUSIONS: The treatment approaches for DTCs used in Italy display areas of inconsistency with those recommended by the 2009 ATA guidelines. Italian practices were characterized by underuse of thyroid lobectomy in intrathyroidal, unifocal DTCs ≤1 cm. The use of RRA was generally consistent with risk-stratified recommendations. However, its frequent use in small DTCs (≤1 cm) that are multifocal persists, despite the lack of evidence of benefit. These data provide a baseline for future assessments of the impact of international guidelines on DTC management in Italy. These findings also illustrate that the dissemination and implementation of guideline recommendations, and the change in practice patterns, require ongoing education and time.
Assuntos
Adenocarcinoma Folicular/terapia , Carcinoma Papilar/terapia , Fidelidade a Diretrizes , Neoplasias da Glândula Tireoide/terapia , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/radioterapia , Carcinoma Papilar/cirurgia , Criança , Medicina Baseada em Evidências , Feminino , Humanos , Radioisótopos do Iodo , Itália , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto JovemRESUMO
Iron oxide nanoparticles (IONP) can have a variety of biomedical applications due to their visualization properties through Magnetic Resonance Imaging (MRI) and heating with radio frequency or alternating magnetic fields. In the oncological field, coating IONP with organic compounds to provide specific features and to achieve the ability of binding specific molecular targets appears to be very promising. To take advantage of the high avidity of tumor cells for glucose, we report the development of very small glucose-coated IONP (glc-IONP) by employing an innovative technique, Metal Vapor Synthesis (MVS). Moreover, we tested the internalization of our gl-IONP on a tumor line, BxPC3, over-expressing GLUT 1 transporter. Both glc-IONP and polyvinylpyrrolidone-IONP (PVP-IONP), as control, were prepared with MVS and were tested on BxPC3 at various concentrations. To evaluate the role of GLUT-1 transporter, we also investigated the effect of adding a polyclonal anti-GLUT1 antibody. After proper treatment, the iron value was assessed by atomic absorption spectrometer, reported in mcg/L and expressed in mg of protein. Our IONP prepared with MVS were very small and homogeneously distributed in a narrow range (1.75-3.75 nm) with an average size of 2.7 nm and were super-paramagnetic. Glc-IONP were internalized by BxPC3 cells in a larger amount than PVP-IONP. After 6h of treatment with 50 mcg/mL of IONPs, the content of Fe was 1.5 times higher in glc-IONP-treated cells compared with PVP-IONP-treated cells. After 1h pre-treatment with anti-GLUT1, a reduction of 41% cellular accumulation of glc-IONP was observed. Conversely, the uptake of PVP-IONPs was reduced only by 14% with antibody pretreatment. In conclusion, MVS allowed us to prepare small, homogeneous, super-paramagnetic glc-IONP, which are electively internalized by a tumor line over-expressing GLUT1. Our glc-IONP appear to have many requisites for in vivo use.
Assuntos
Portadores de Fármacos/metabolismo , Endocitose/fisiologia , Transportador de Glucose Tipo 1/genética , Nanopartículas de Magnetita/química , Pâncreas/metabolismo , Anticorpos/farmacologia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Compostos Férricos/química , Expressão Gênica , Glucose/química , Glucose/metabolismo , Transportador de Glucose Tipo 1/antagonistas & inibidores , Transportador de Glucose Tipo 1/metabolismo , Humanos , Nanopartículas de Magnetita/ultraestrutura , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Tamanho da Partícula , Povidona/química , VolatilizaçãoRESUMO
The mutation BRAF V600E is thought to be a putative prognostic marker of the aggressiveness of several cancers among which is also papillary thyroid cancer. Our study aimed to evaluate whether this mutation is associated with advanced stages of disease or with a worse prognosis in a series of patients with cytological findings of Thyr 4 and Thyr 5 and who were undergoing total thyroidectomy and routine central compartment lymph-node dissection. 110 patients were consecutively enrolled over an 18-month period from September 2010 to March 2012. All patients had cytological findings that were either indicative of, or positive for papillary thyroid cancer, Thyr 4 or Thyr 5. Detection of BRAF mutation was made on fine-needle aspiration specimen by pyrosequencing after microdissection and DNA extraction of neoplastic cells. After surgical intervention, the patients underwent radioiodine ablation according to our protocol, and follow-up was performed after 8 months. The BRAF V600E mutation was found in 79 % of our cases: 85.7 % of these cases represented the classical variant, 57.8 % the follicular variant, 89.6 % the tall cell variant, and 33.3 % the solid variant. All patients had confirmation of papillary thyroid cancer after histology, with no differences being seen in pTNM presentation between patients with BRAF wild-type and patients with BRAF V600E mutation. Ninety-nine patients underwent radioiodine ablation. Results at follow-up 8 months after radioiodine ablation showed no differences in the rate of ablation between patients harboring BRAF V600E mutation and those having BRAF wild-type. The BRAF V600E mutation doesn't appear to be a reliable risk factor for the aggressiveness of a tumor. BRAF analysis should neither be the only guide for pre-surgical decisions regarding the extent of surgery nor for post-surgical decisions regarding the aggressiveness of the treatment.
Assuntos
Biomarcadores Tumorais , Carcinoma/genética , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Biópsia por Agulha Fina , Carcinoma/patologia , Carcinoma/radioterapia , Carcinoma/cirurgia , Carcinoma Papilar , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mutação/genética , Gradação de Tumores , Estadiamento de Neoplasias , Análise de Sequência de DNA/instrumentação , Análise de Sequência de DNA/métodos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
Pituitary metastases (PM) from thyroid cancer are rare, but their management can represent a difficult challenge for the endocrinologist. Our aim was to review all reported cases of PM from thyroid cancer. PubMed was consulted and 19 papers reporting 20 cases were found. We moreover discuss two of our own cases, which had come to our attention within a few months of one another. Eleven cases were follicular cancer, eight cases were papillary cancer, two cases were medullary cancer, and one case was an insular cancer. In nine cases, PM was the first sign of the disease. Cranial nerve involvement was the most common sign of its presence, and no neuroradiological imaging could lead to a sure diagnosis of PM. Neurosurgical intervention was performed in almost all cases, and post-surgical treatment comprised radioiodine, external beam radiotherapy, and radiosurgery. Prognosis was poor for larger metastases, cranial nerve palsy disappeared in only one case, and in only one case of intrasellar metastasis was the disease cured. PM from thyroid cancer are rare, but are burdened by a poor prognosis. An early diagnosis appears important, and a comprehensive strategy for treatment (neurosurgery, radioiodine, external radiotherapy, and radiosurgery) appears advisable.
Assuntos
Adenocarcinoma Folicular/secundário , Carcinoma Medular/secundário , Carcinoma Papilar/secundário , Neoplasias Hipofisárias/secundário , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/cirurgia , Carcinoma Medular/cirurgia , Carcinoma Papilar/cirurgia , Humanos , Hipófise/patologia , Hipófise/cirurgia , Neoplasias Hipofisárias/cirurgia , Prognóstico , Radiocirurgia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
BACKGROUND AND AIM: Recombinant human TSH (rhTSH) can be used for post-surgical radioiodine (I-131) thyroid remnants ablation in differentiated thyroid cancer (DTC) patients after surgery. Debate exists in literature about the optimal amount of I-131 that should be given for obtaining an effective ablation and about the role of iodine pool during treatment. Therefore, the aim of the present study was to assess whether I-131 ablation during rhTSH stimulus can be improved by reducing the circulating iodine pool and by increasing thyroid cell uptake and retention of I-131 obtained by administering furosemide and lithium. METHODS: A total of 201 consecutive DTC patients were entered in the study: they were treated by total thyroidectomy and I-131 therapy during rhTSH stimulus to ablate thyroid remnants. Patients were divided into two groups according to the TNM stage: group 1 included patients in stage I-II who were treated with a low 30-mCi I-131 dose, while group 2 included patients in stage III-IV who were treated by a high 100-mCi I-131 dose. Moreover, both groups were further subdivided into three subgroups. Subgroup (a) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-thyroxine (LT4). Subgroup (b) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-T4, and after furosemide administration (25 mg/day orally) during the 3 days before I-131. Subgroup (c) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day L-T4 withdrawal, and after administration of furosemide (25 mg/day orally) during the 3 days prior I-131 and lithium (450 mg/day orally) during the 3 days following I-131. Another group (group 3) of 20 patients characterized by a very low-risk cancer (unifocal tumor <1.0 cm in diameter, without extra-capsular extension, N0) was treated with a 30-mCi I-131 dose under rhTSH stimulus without performing the short 4-day L-4 withdrawal: this group was taken as the control. Follow-up was performed by neck ultrasonography (US), and Tg measurement and I-131 WBS under rhTSH stimulus. RESULTS: Among the patients from group 1, those pre-treated with furosemide or with furosemide plus lithium showed a better outcome of ablation both in terms of undetectable Tg values (97.7% and 95.5 % vs. 79.5%, p < 0.05) and of WBS negativity (97.7% vs. 81.8%, p < 0.05) during the rhTSH stimulus. No similar findings were observed in group 2 patients. Moreover, in patients from group 3 (I-131 30 mCi, without L-T4 withdrawal), the outcome of ablation was significantly lower in comparison to patients from group 1 (I-131 30 mCi, with L-T4 withdrawal) in terms of undetectable Tg during the rhTSH stimulus (55.0%, p < 0.001). CONCLUSION: rhTSH is highly effective for post-surgical thyroid remnant ablation in low-risk cancer patients using the low 30-mCi dose protocol combined with the short 4-day withdrawal of L-T4. Moreover, in these patients the pre-treatment with furosemide seems to play an important role to further improve the outcome of ablation by reducing the iodine pool.