Background
Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent.
Methods
Six scientific Italian societies entitled to cure thyroid ...cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field.
Objective
The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.
•This special article provides updated treatment recommendations on thyroid cancer.•New targeted systemic therapies have now been approved for treating patients with advanced/metastatic thyroid ...cancers.•This article summarises these new options and the order in which they should be used.•Recommendations are based on available scientific data and the authors’ collective expert opinion.•ESCAT scores are given to describe the evidence level for genomic alterations as biomarkers for using targeted therapies.•Authorship includes a multidisciplinary group of thyroid cancer experts.
Background
Current management options for PTMC include lobo-isthmectomy and active surveillance (AS). Recently, ultrasound-guided minimally invasive procedures (MITs) are offered as a nonsurgical ...therapy for PTMC because they do not require hospitalization and general anaesthesia, and do not result in loss of thyroid function or cosmetic damage. MITs are reported to consistently provide, mostly in large retrospective series of patients, a rapid, safe, and cost-effective way to eradicate low-risk thyroid malignancies. However, conclusive data from well-conducted prospective studies on the histologically-proven completeness of tumor ablation and the long-term clinical advantages versus AS are still lacking.
Objectives
This study aimed to evaluate the efficacy and safety of ultrasound-guided minimally invasive treatments (MITs) for PTMC in comparison to traditional surgical methods and active surveillance, and to assess their role in current clinical practice.
Methods
A structured literature review was conducted using keywords related to PTMC, MIT, and comparative techniques. Studies were evaluated based on treatment modality, patient selection, follow-up duration, complication rates, and clinical outcomes.
Results
MITs have shown promising results in the management of PTMC. These treatments offer several advantages over surgery, such as reduced use of surgical resources, lower costs, minimal work disruption, and fewer major complications. However, there are still limitations, including the need for long-term surveillance and the potential risk of incomplete tumor ablation.
Conclusions
MITs represent a promising non-surgical option for managing low-risk PTMC, especially for patients ineligible for or refusing surgery. Despite favorable outcomes, more robust prospective data are needed to confirm their long-term benefits and completeness of tumor ablation. Interdisciplinary discussions and thorough patient education on the advantages and limitations of MITs are crucial for informed decision-making.
Nuclear magnetic resonance (NMR) spectroscopy is one of the well-established tools for food metabolomic analysis, as it proved to be very effective in authenticity and quality control of dairy ...products, as well as to follow product evolution during processing and storage. The analytical assessment of the EU mountain denomination label, specifically for Parmigiano Reggiano "Prodotto di Montagna - Progetto Territorio" (Mountain-CQ) cheese, has received limited attention. Although it was established in 2012 the EU mountain denomination label has not been much studied from an analytical point of view. Nonetheless, tracing a specific profile for the mountain products is essential to support the value chain of this specialty.
The aim of the study was to produce an identity profile for Parmigiano Reggiano “Prodotto di Montagna - Progetto Territorio” (Mountain-CQ) cheese, and to differentiate it from Parmigiano Reggiano PDO samples (conventional-PDO) using 1H NMR spectroscopy coupled with multivariate data analysis. Three different approaches were applied and compared. First, the spectra-as-such were analysed after proper preprocessing. For the other two approaches, Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) was used for signals resolution and features extraction, either individually on manually-defined spectral intervals or by reapplying MCR-ALS on the whole spectra with selectivity constraints using the reconstructed “pure profiles” as initial estimates and targets. All approaches provided comparable information regarding the samples’ distribution, as in all three cases the separation between the two product categories conventional-PDO and Mountain-CQ could be highlighted. Moreover, a novel MATLAB toolbox for features extraction via MCR-ALS was developed and used in synergy with the Chenomx library, allowing for a putative identification of the selected features.
A first identity profile for Parmigiano Reggiano “Prodotto di Montagna - Progetto Territorio” obtained by interpreting the metabolites signals in NMR spectroscopy was obtained. Our workflow and toolbox for generating the features dataset allows a more straightforward interpretation of the results, to overcome the limitations due to dimensionality and to peaks overlapping, but also to include the signals assignment and matching since the early stages of the data processing and analysis.
•For the first time a NMR metabolomic characterization of Parmigiano Reggiano “Prodotto di Montagna - Progetto Territorio” was obtained.•A MATLAB toolbox was developed allowing pure metabolites profiles determination and putative identification.•It has been possible to highlight metabolites capable to differentiate Mountain Parmigiano Reggiano from conventional Parmigiano Reggiano PDO cheese.
Lenvatinib is a multi-kinase inhibitor approved for patients with radioactive iodine (RAI)–resistant differentiated thyroid cancer (DTC). Before the drug approval from the Italian National Regulatory ...Agency, a compassionate use programme has been run in Italy. This retrospective study aimed to analyse data from the first series of patients treated with lenvatinib in Italy.
The primary aim was to assess the response rate (RR) and progression-free survival (PFS). Secondary end-points include overall survival (OS) and toxicity data.
From November 2014 to September 2016, 94 patients were treated in 16 Italian sites. Seventeen percent of patients had one or more comorbidities, hypertension being the most common (60%). Ninety-eight percent of patients were treated by surgery, followed by RAI in 98% of cases. Sixty-four percent of patients received a previous systemic treatment. Lenvatinib was started at 24 mg in 64 subjects. Partial response and stable disease were observed in 36% and in 41% of subjects, respectively; progression was recorded in 14% of patients. Drug-related side-effects were common; the most common were fatigue (13.6%) and hypertension (11.6%). Overall, median PFS and OS were 10.8 months (95% confidence interval CI, 7.7–12.6) and 23.8 months (95% CI, 19.7–25.0) respectively.
Lenvatinib is active and safe in unselected, RAI-refractory, progressive DTC patients in real-life setting. RR and PFS seem to be less favourable than those observed in the SELECT trial, likely due to a negative selection that included heavily pretreated patients or with poor performance status.
•Patients with metastatic differentiated thyroid cancer (DTC) have poor survival rate.•Lenvatinib improved clinical outcomes in patient with metastatic radioactive iodine-refractory DTC.•Lenvatinib is active and safe, even in a real-life patient population.•Older patients show survival benefit from lenvatinib, without safety concern.
Context: BRAF mutations are common in papillary thyroid carcinomas (PTCs). By affecting the expression of genes critically related to the development and differentiation of thyroid cancer, they may ...influence the prognosis of these tumors.
Objective: Our objective was to characterize the expression of thyroid-specific genes associated with BRAF mutation in PTCs.
Design/Setting and Patients: We examined the expression of key markers of thyrocyte differentiation in 56 PTCs with BRAF mutations (BRAF-mut) and 37 with wild-type BRAF (BRAF-wt). Eight samples of normal thyroid tissue were analyzed as controls. Quantitative PCR was used to measure mRNA levels for the sodium/iodide symporter (NIS), apical iodide transporter (AIT-B), thyroglobulin (Tg), thyroperoxidase (TPO), TSH receptor (TSH-R), the transcription factor PAX8, and glucose transporter type 1 (Glut1). NIS protein expression and localization was also analyzed by immunohistochemistry.
Results: mRNA levels for all thyroid-specific genes were reduced in all PTCs vs. normal thyroid tissues. NIS, AIT-B, Tg, and TPO expression was significantly lower in BRAF-mut tumors than in the BRAF-wt group. Glut-1 transcript levels were increased in all PTCs, and additional increases were noted in BRAF-mut tumors. In both tumor subsets, the NIS protein that was expressed was abnormally retained in the cytoplasm.
Conclusion: BRAF V600E mutation in PTCs is associated with reduced expression of key genes involved in iodine metabolism. This effect may alter the effectiveness of diagnostic and/or therapeutic use of radioiodine in BRAF-mut PTCs.
Aim: The goal of this study was to estimate the cumulative activity of 131I to be administered to patients with distant metastases from thyroid carcinoma.
Methods: A total of 444 patients were ...treated from 1953–1994 for distant metastases from papillary and follicular thyroid carcinoma: 223 had lung metastases only, 115 had bone metastases only, 82 had both lung and bone metastases, and 24 had metastases at other sites. Treatment consisted of the administration of 3.7 GBq (100 mCi) 131I after withdrawal of thyroid hormone treatment, every 3–9 months during the first 2 yr and then once a year until the disappearance of any metastatic uptake. Thyroxine treatment was given at suppressive doses between 131I treatment courses.
Results: Negative imaging studies (negative total body 131I scans and conventional radiographs) were attained in 43% of the 295 patients with 131I uptake; more frequently in those who were younger, had well-differentiated tumors, and had a limited extent of disease. Most negative studies (96%) were obtained after the administration of 3.7–22 GBq (100–600 mCi). Almost half of negative studies were obtained more than 5 yr after the initiation of the treatment of metastases. Among patients who achieved a negative study, only 7% experienced a subsequent tumor recurrence. Overall survival at 10 yr after initiation of 131I treatment was 92% in patients who achieved a negative study and 19% in those who did not.
Conclusion: 131I treatment is highly effective in younger patients with 131I uptake and with small metastases. They should be treated until the disappearance of any uptake or until a cumulative activity of 22 GBq has been administered. In the other patients, other treatment modalities should be used when tumor progression has been documented.
The mercury (Hg) pollution of sediments is the main carrier of Hg for the biota and, subsequently, for the local fish consumers in Augusta Bay area (SE Sicily, Italy), a coastal marine system ...affected by relevant sewage from an important chlor-alkali factory. This relationship was revealed by the determination of Mass Dependent (MDF) and Mass Independent Fractionation (MIF) of Hg isotopes in sediment, fish and human hair samples. Sediments showed MDF but no MIF, while fish showed MIF, possibly due to photochemical reduction in the water column and depending on the feeding habitat of the species. Benthic and demersal fish exhibited MDF similar to that of sediments in which anthropogenic Hg was deposited, while pelagic organisms evidenced higher MDF and MIF due to photoreduction. Human hair showed high values of δ202Hg (offset of +2.2‰ with respect to the consumed fish) and Δ199Hg, both associated to fish consumption.
•We report the Hg isotope ratios of sediments, fish and human hair in Augusta Bay.•Hg isotopes show mercury transfers from sediments to benthic and demersal fish.•MIF in fish appears to be driven by effect of photoreduction.•MIF in human hair is inherited by fish consumption.
The mercury (Hg) isotope composition of sediments, fish muscles and human hair has been investigated from the highly polluted Augusta Bay (SE Sicily, Italy).
Purpose and Patients
The M.O.S.CA.TI. (Metastases of the Skeleton from CArcinoma of the ThyroId) is a multicenter, retrospective study investigating the real-life outcome and management of bone ...metastases (BM) in 143 patients (63 M, 80 F; median age 64 years, range 11–87) with differentiated thyroid carcinoma (DTC).
Results
Radio-active iodine (RAI) treatment was performed in 131 patients (91.6%), surgical approach and/or external radiotherapy in 68 patients (47.6%), and anti-resorptive bone-active drugs in 32 patients (22.4%; in 31 zoledronate and in one denosumab). At the start of treatment, 24 patients (75.0%) receiving anti-resorptive bone-active drugs had at least one clinical skeletal-related event (SRE) (
p
< 0.001). One or more clinical SREs (pathological fractures and/or malignant hypercalcemia and/or spinal cord compression) developed in 53 patients (37.1%). Development of SREs was significantly associated with metachronous BM (hazard ratio (HR) 2.04;
p =
0.04), localization of BM to cervical spine (HR 3.89;
p =
0.01), and lack of avid RAI uptake (HR 2.66;
p =
0.02). Thirty-nine patients (27.3%) died in correlation with development of SREs (HR 6.97;
p =
0.006) and localization of BM to the hip (HR 3.86;
p =
0.02). Moreover, overall mortality was significantly decreased by RAI therapy (HR 0.10;
p =
0.02), whereas no significant effects were induced by bone-active drugs (
p =
0.36), external radiotherapy (
p =
0.54), and surgery (
p =
0.43) of BM.
Conclusions
SREs are very frequent in BM from DTC and they impact patient survival. In the real life, the use of bone-active drugs is currently limited to zoledronate in patients with pre-existing SREs. In this clinical setting, RAI therapy, but not zoledronate, decreased mortality.
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