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.
Medullary Thyroid Carcinoma Pacini, F; Castagna, M.G; Cipri, C ...
Clinical oncology (Royal College of Radiologists (Great Britain)),
08/2010, Volume:
22, Issue:
6
Journal Article
Peer reviewed
Abstract Medullary thyroid carcinoma (MTC) accounts for 5–8% of all thyroid cancers. MTC is mainly sporadic in nature, but an hereditary pattern multiple endocrine neoplasia type 2 (MEN 2) is present ...in 20–30% of cases, transmitted as an autosomal-dominant trait due to germline mutations of the RET proto-oncogene. About 98% of patients with MEN 2 have germline mutations in exons 5, 8, 10, 11, 13, 14, 15 or 16 of the RET gene. The primary treatment of both hereditary and sporadic forms of MTC is total thyroidectomy and removal of all neoplastic tissue present in the neck. The therapeutic option for lymph node surgery should be dictated by the results of presurgical evaluation. After total thyroidectomy, measurements of serum calcitonin (CT) and carcinoembryonic antigen are of paramount importance in the postsurgical follow-up of patients with MTC as they reflect the presence of persistent or recurrent disease. Complete remission is demonstrated by undetectable and stimulated serum CT measurement. On the contrary, if serum CT is detectable under basal conditions or becomes detectable after stimulation, the patient is probably not cured, but imaging techniques will not demonstrate any disease until serum CT approaches levels >150 pg/ml. The tumour metastasises early to both paratracheal and lateral cervical lymph nodes. Metastases outside the neck may occur in the liver, lungs, bones and, less frequently, brain and skin. Surgery is the main treatment for local and distant metastases whenever feasible. Systemic chemotherapy with dacarbazine, 5-fluorouracil and doxorubicin (alone or in combination) has shown very limited efficacy, achieving only partial responses in the range of 10–20% and of short duration. Several kinase inhibitors are currently under evaluation and preliminary results are promising. Familial cases must be identified by searching for RET proto-oncogene mutations in the proband and in family members. Carriers of the RET gene are candidates for prophylactic thyroidectomy at different ages depending on the risk associated with the specific RET mutations.
Purpose
Immunotherapy against immune checkpoints has significantly improved survival both in metastatic and adjuvant setting in several types of cancers. Thyroid dysfunction is the most common ...endocrine adverse event reported. Patients who are at risk of developing thyroid dysfunction remain to be defined. We aimed to identify predictive factors for the development of thyroid dysfunction during immunotherapy.
Methods
This is a retrospective study including a total of 68 patients who were treated with immune checkpoint inhibitors (ICIs) for metastatic or unresectable advanced cancers. The majority of patients were treated with anti-PD1 drugs in monotherapy or in combination with anti-CTLA4 inhibitors. Thyroid function and anti-thyroid antibodies, before starting immunotherapy and during treatment, were evaluated. Thyroid ultrasound was also performed in a subgroup of patients at the time of enrolment in the study.
Results
Eleven out of 68 patients (16.1%) developed immune-related overt thyroid dysfunction. By ROC curve analysis, we found that a serum TSH cut-off of 1.72 mUI/l, at baseline, had a good diagnostic accuracy in identifying patients without overt thyroid dysfunction (NPV = 100%,
p
= 0.0029). At multivariate analysis, both TSH and positive anti-thyroid antibodies (ATAbs) levels, before ICIs treatment, were independently associated with the development of overt thyroid dysfunction during immunotherapy (
p
= 0.0001 and
p
= 0.009, respectively).
Conclusions
Pre-treatment serum TSH and ATAbs levels may help to identify patients at high risk for primary thyroid dysfunction. Our study suggests guidance for an appropriate timely screening and for a tailored management of thyroid dysfunctions in patients treated with ICIs.
Radioactive iodine therapy is administered to patients with differentiated thyroid cancer (DTC) for eradication of thyroid remnant after total thyroidectomy or, in patients with metastatic disease, ...for curative or palliative treatment. In past years, thyroid remnant ablation was indicated in almost every patient with a diagnosis of DTC. Nowadays, careful revision of patients’ outcome has introduced the concept of risk-based selection of patients candidate to thyroid remnant ablation. The present review aims to underline the indications for thyroid remnant ablation and to address methodologies to be employed.
Trypanosoma cruzi, the agent of Chagas disease, can infect through conjunctive or oral mucosas. Therefore, the induction of mucosal immunity by vaccination is relevant not only to trigger local ...protection but also to stimulate both humoral and cell-mediated responses in systemic sites to control parasite dissemination. In a previous study, we demonstrated that a nasal vaccine based on a Trans-sialidase (TS) fragment plus the mucosal STING agonist c-di-AMP, was highly immunogenic and elicited prophylactic capacity. However, the immune profile induced by TS-based nasal vaccines at the nasopharyngeal-associated lymphoid tissue (NALT), the target site of nasal immunization, remains unknown. Hence, we analyzed the NALT cytokine expression generated by a TS-based vaccine plus c-di-AMP (TSdA+c-di-AMP) and their association with mucosal and systemic immunogenicity. The vaccine was administered intranasally, in 3 doses separated by 15 days each other. Control groups received TSdA, c-di-AMP, or the vehicle in a similar schedule. We demonstrated that female BALB/c mice immunized intranasally with TSdA+c-di-AMP boosted NALT expression of IFN-γ and IL-6, as well as IFN-β and TGF-β. TSdA+c-di-AMP increased TSdA-specific IgA secretion in the nasal passages and also in the distal intestinal mucosa. Moreover, T and B-lymphocytes from NALT-draining cervical lymph nodes and spleen showed an intense proliferation after ex-vivo stimulation with TSdA. Intranasal administration of TSdA+c-di-AMP provokes an enhancement of TSdA-specific IgG2a and IgG1 plasma antibodies, accompanied by an increase IgG2a/IgG1 ratio, indicative of a Th1-biased profile. In addition, immune plasma derived from TSdA+c-di-AMP vaccinated mice exhibit in-vivo and ex-vivo protective capacity. Lastly, TSdA+c-di-AMP nasal vaccine also promotes intense footpad swelling after local TSdA challenge. Our data support that TSdA+c-di-AMP nasal vaccine triggers a NALT mixed pattern of cytokines that were clearly associated with an evident mucosal and systemic immunogenicity. These data are useful for further understanding the immune responses elicited by the NALT following intranasal immunization and the rational design of TS-based vaccination strategies for prophylaxis against T. cruzi.
Introduction
MiRNAs are small endogenous non-coding RNAs implicated with gene expression regulation. Changes in miRNA levels have been reported in thyroid cancer. Fine-needle aspiration cytology ...(FNAC) is the most reliable tool for differential diagnosis of thyroid nodules.
Methods
We have analyzed 174 FNAC from 168 patients with thyroid nodules for expression levels of 11 miRNAs (miRNA197; -187; -181b-3p; -181b-5p; -224; -181a; 146b; -221; -222; -155 and miRNA183) known to be up-regulated in cancer tissues compared to benign lesions. Expression of miRNAs was analyzed in FNA samples calculating the fold change of miRNA expression relative to normal thyroid tissue after normalization to an endogenous control.
Results
In FNAC, miRNA expression was confirmed to be higher in malignant or suspicious for malignancy nodules compared to benign, only for miRNA146b, -222 and -221 (fold change expression ≥ 5).
Conclusion
In this study, we confirmed that a limited set of miRNAs can be used for the differential diagnosis of thyroid nodules.
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