Follicular thyroidcancer and papillary thyroidcancer show different patterns of spread. The former has a higher propensity to disseminate to bones (7-28% versus 1.4-7% for with papillary thyroidcancer), probably due to a higher frequency of haematogenous dissemination (10,18). However, in absolute terms, in our study we found a greater number of patients with papillary carcinoma and BM, similar to that reported in other series (19). This finding is probably related to the overall higher incidence of papillary thyroidcancer compared to follicular thyroidcancer that, in most current series, comprises only 4 to 7% of the cases.
Table 2 and Figure 2 show risk estimates for DM-associated thyroidcancer risk in all studies and subgroups according to study design, geographic region, and study quality. People with type 2 DM were at an increased risk for thyroidcancer relative to non- diabetic people in all studies combined (RR = 1.34, 95% CI 1.11– 1.63). However, there was heterogeneity across the studies (p- heterogeneity,0.0001). For the sensitivity analysis, we excluded the studies which reported risk estimates of SIR [14,32] and had different definition of DM [33,34]. When we excluded these studies, people in 9 studies remaining after sensitivity testing showed about a 20% increased risk of thyroidcancer associated with pre-existing DM (RR 1.18, 95% CI 1.08–1.28) (Figure 2-(a)). In the cohort studies, DM was associated with a greater increased risk for thyroidcancer (RR 1.18, 95% CI 1.09–1.09) without any heterogeneity (p for heterogeneity = 0.76) and no evidence for publication bias (p by Egger test = 0.39) (Figure 2-(b)). The risk estimate for case-control studies resulted in a relative risk of 0.91 (95% CI 0.51–1.64) which were estimated from the 2 studies. The results for studies from countries with a high incidence of thyroidcancer were similar to the results overall (RR 1.18, 95% CI 1.09– 1.29). In low-rate geographic areas, the thyroidcancer risk associated with DM was no longer apparent. In high quality studies, type 2 DM was associated with a RR of thyroidcancer of 1.18 (95% CI 1.08–1.28) after sensitivity testing.
Clinical profiles, presentation at diagnosis, ultrasound features, management received, cancer staging, clinical course, tumor recurrence, and eventual outcome were all documented and de- scribed. Patients with incomplete data or diagnostic tests were still included in the study and reported accordingly. All data were then tabulated and recorded using a descriptive statistical analysis (mean, median, mode, and standard deviation). Tumor recurrence was assessed only after thyroidectomy and expressed in terms of the number of months post-thyroid- ectomy. It was considered and reported if one of the following was present: (1) elevated stimulated (>1 µg/L) or unstimulated (>2 µg/L) serum thyroglobulin after thyroidectomy and radio- active ablation; (2) recurrent or new-onset lymphadenopathies proven to be thyroidcancer by biopsy or radioiodine scan; and (3) recurrent or new-onset distant metastases proven to be thy- roid cancer by biopsy or radioiodine scan.
Although some cases of thyroidcancer may have been misclassified, such an occurrence was probably low in the present study because labeled diagnoses should be printed on all prescriptions handed out to patients in Taiwan. Mislabeling of a cancer diagnosis would not be acceptable to patients when they saw the diagnosis. In secondary sensitivity analyses when the definition of thyroidcancer was restricted to the patients who had been issued a Severe Morbidity Card bearing a diagnosis of thyroidcancer, the results were similar and the conclusions remained unchanged (data not shown). The impact of a higher probability of receiving potential detection examinations in the diabetic patients was also minimal, because the odds ratios seen in Tables 2 and 3 would not remarkably change if the covariate of ‘‘potential detection examinations’’ was not entered into the models (data not shown).
Given the association between miR-126-3p expression and aggressive thyroidcancer disease phenotype, we wanted to determine if the function of miR-126-3p in thyroidcancer could mechanistically explain this association. We overexpressed miR-126-3p in three well-charac- terized and authenticated thyroidcancer cell lines (TPC-1, FTC-133 and XTC-1) using miR-NC as a negative control to determine its effect on cellular proliferation. miR-126-3p overexpression inhibited cell proliferation significantly in TPC-1 and FTC-133 cells at 120 hours, by 52% (p<0.001) and 37% (p<0.001), respectively; however, it inhibited proliferation only by 16% in XTC-1 cells at 168 hours (p<0.001) (Fig 2A, 2B and 2C). A soft agar colony for- mation assay was performed to evaluate anchorage-independent growth in FTC-133, which is a colony-forming thyroidcancer cell line. We found a significantly lower number of colonies in FTC-133 cell lines overexpressing miR-126-3p (Fig 2D). We also studied the effect of miR- 126-3p on thyroidcancer cell tumor spheroid formation. The FTC-133 and XTC-1 cell lines form spheroids when cultured in ultra-low adherent culture flasks, and after transfection with miR-126-3p, the number and size of spheroids were significantly decreased (Fig 2E).
Thyroid nodules are frequent indings, especially when sensitive imaging methods are used. Al- though thyroidcancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroidcancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their morta- lity rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants’ experience and a review of the relevant literature. Arq Bras Endocrinol Metab. 2013;57(4):240-64
In search of new cancer biomarkers for this malignancy, we analyzed the secretome from thyroidcancer cell lines to identify cancer-relevant secreted proteins that can serve as potential biomarkers . One of the candidate proteins identified in our study was biotinidase, an enzyme that catalyzes the hydrolysis of biocytin, the product of biotin-dependent carboxylase degrada- tion, to biotin and lysine. Biotin deficiency may lead to the decreased activity of holocarboxylase synthetase, an enzyme which mediates the binding of biotin to histones , a crucial component of epigenetic events that regulate chromatin structures and gene function. Low level of biotinidase was observed in aggressive anaplastic derived cell line (CAL-62) as compared to the non- aggressive papillary derived thyroidcancer cell line (TPC-1). The clinical relevance was suggested by demonstrating reduced levels of biotinidase in aggressive thyroidcancer patients’ sera as compared to the non-aggressive and benign patients’ sera by western blotting . In the current study, our main objective was to determine the clinical significance of biotinidase as a marker to distinguish benign thyroid and malignant tumors as well as to stratify aggressive and non-aggressive PTC that could serve as a potential tool for improved management of this malignancy.
There are several limitations to our study. Firstly, the generalizability of our findings maybe limited because the participants were recruited from only two tertiary/quaternary care academic institutions in the same city. The demographic characteristics of our participants (approximately three-quarters women and mean age in the mid-forties), are in keeping with general population thyroidcancer statistics (76% of new thyroidcancer cases are in women in Canada  and the mean age of diagnosis in the Surveillance, Epidemiology, and End Results Program in the United States is 46 years ). All participants in this study were English-speaking and many of them were highly educated, which may limit the applicability of our findings to other populations. Moreover, the prevalence of disease recurrence in our study group (approximately one-third), was higher than one would expect expected for early stage papillary thyroidcancer (an average cumulative incidence of 9.3% at 10 years) . In our study, more than half of participants reported one or more short- or long-term side effects attributed to RAI treatment, which is higher than the 29% rate of short-term side effects reported in the thyroid hormone withdrawal group for a recent efficacy study of remnant ablation . It is possible that there may be some recruitment bias in our sample as individuals with recurrent or more complex disease features may have been more likely to be followed in the tertiary/quaternary care environment of our institutions than in the community. Also, some individuals who were initially treated at other institutions may have been referred to our institution for treatment of recurrent disease. Some of the treatment-related side effects reported by participants may have been a reflection of more intensive therapy administered in a tertiary care environment where complex cases are often seen. Also, it is possible that participants who had particularly negative experiences after their
Treatment protocol was done in accordance with the American thyroidcancer guideline . Briefly, about one month after total thyroidectomy, patients with DTC were given 131 I for thyroid ablation (approximately 100 mCi). Five days after 131 I administration, whole body scan and tomographic imaging were performed by using a dual-detector single photon emission computed tomography (SPECT)/CT equipped with high-energy collimators (Discovery NM/ CT 670; General Electric Medical Systems, Milwaukee Wisconsin, USA). Clinical assessments (including evaluation of thyroid remnant uptake and whether metastases existed) were con- ducted after reading the 131 I scans. Then patients were divided into two subgroups, namely, subgroup 1 DTC with metastases, and subgroup 2 DTC without metastases. Patients were closely followed for at least 6 months. Repeated 131 I therapies were given with intervals of ap- proximately 6 months, if obvious residue thyroid tissue existed or metastases were detected.
Throughout cancer development, several genetic changes occur that deregulate different signalling pathways controlling cancer survival, progression and invasion. The most common genetic alterations involved in papillary thyroidcancer include BRAF V600E point mutation and RET/PTC rearrangements, affecting positively the activity of the pro-tumorigenic MAPK pathway. Nonetheless, RET/PTC rearrangements can also activate the PI3K/Akt/mTOR pathway. Besides, RAS activating mutations have been detected in PTC patients and, similar to RET/PTC, can signal through both MAPK and PI3K/Akt/mTOR pathways. Thus, despite MAPK being considered the main signalling pathway involved in thyroidcancer oncogenesis, PI3K/Akt/mTOR can be expected to play an important role during this process. Therefore, targeting the PI3K/Akt/mTOR pathway becomes an attractive therapeutic option, also in the context of thyroidcancer.
The prevalence of thyroidcancer is increasing in many parts of the world, although this is likely due to increased detection of small tumors based on enhanced diagnostic procedures [16- 20]. FNA is safe, easy to perform, and the most important test for diagnosis of thyroidcancer; as a result, increasing numbers of clinicians are learning the FNA procedure. The purpose of the present study was to determine the effect of operator expe- rience on FNA performance. There was no difference in the sample adequacy rate between experienced and inexperienced operators. However, more false-negative results occurred Table 4. Comparison of Fine-Needle Aspiration Diagnostic In-
Thyroidcancer is the most common malignancy of the endocrine system, represents more than 1% of all malignancies and has an estimated annual incidence of 212,000 cases worldwide. The term differentiated thyroid carcinoma (DTC) comprises the subtypes papillary thyroid carcinoma (PTC) and follicular thyroid carcinomas (FTC), these subtypes represent the two most common subtypes of thyroidcancer (approximately 80% and 10% respectively). Despite its incidence DTCs have a good prognosis with relatively few metastases and deaths associated. The polymorphisms (variants in DNA sequence among individuals that have a frequency of at least 1% in a population) of RET proto-oncogene have been studied in different populations for association with susceptibility to thyroidcancer, but with inconsistent findings mainly in DTC. To clarify the contribution of single locus or haplotypes (polymorphisms that are transmitted through generations as a unit) of RET polymorphisms to genetic susceptibility to DTC among Portuguese patients, we conducted a case–control study by analyzing four well-characterized RET polymorphisms (G691S, L769L, S836S and S904S).
Thyroidcancer cells were seeded at a density of 5x10 6 cells per plate, and grown in RPMI-1640 media supplemented with 5% FBS for 6 hours. Media was then aspirated and replaced with the media supplemented with 0.1% FBS, and cells were incubated for 18 hours. Cells were har- vested and 1x10 6 cells were seeded in the upper chambers of Matrigel-coated transwell cham- bers (24-well, 8 μm pore size; BD Biosciences) in RPMI-1640 with 0.1% FBS. Assays were carried out in duplicate. Cells invaded into the lower chamber containing media with 10% FBS. After 18 hours, non-invading cells in the top chamber were discarded, and invading cells were fixed with methanol, stained with 3 μg/mL 4’,6-diamidino-2-phenylindole (DAPI; Invitrogen) and counted in five microscopic fields under 10x magnification using Metamorph software (Molecular Devices).
Additionally, there are different codes to describe the same procedure, for example, “total thyroidectomy” versus “total thyroidectomy in oncology”. This study considered only the code for total thyroidectomy in oncology, which excludes thyroid surgeries for benign diseases. However, the figures may be underestimated, as it is possible that the code for total thyroidectomy (not oncologic) also might have been used to describe surgeries for cancer. Another coding problem is that the code used to describe thyroid FNAB because it is used to describe thyroid as well as parathyroid FNAB. It is known that thyroid tumors are 16 times more common than parathyroid tumors (50). We therefore assumed all FNAB were related to thyroidcancer. Although this may result in a small overestimation of its use, there has been no change in the incidence of parathyroid tumors, and the documented increase over the last eight years is unlikely to have changed if the cases used for parathyroid disease were excluded. Finally, the treatment related-procedure codes that referred to other diseases despite thyroidcancer were disregarded as they might have overestimated the results.
Globally, thyroidcancer accounts for 2 % of all cancer diagnoses, and can be classified as well-differentiated or undifferentiated. Currently, differentiated thyroid carcinomas have good prognoses, and can be treated with a combination of therapies, including surgical thyroidectomy, radioactive iodine therapy and hormone-based ther- apy. On the other hand, anaplastic thyroid carcinoma, a subtype of undifferentiated thyroid carcinoma character- ized by the loss of thyroid-like phenotype and function, does not respond to either radioactive iodine or hormone therapies. In most cases, anaplastic thyroid carcinomas are diagnosed in later stages of the disease, deeming them inoperable, and showing poor response rates to systemic chemotherapy. Recently, treatment courses using multi- ple-target agents are being explored and clinical trials have shown very promising results, such as overall survival rates, progression-free survival and tumor shrinkage. This review is focused on thyroid carcinomas, with particular focus on anaplastic thyroid carcinoma, exploring its undifferentiated nature. Special interest will be given to the treatment approaches currently available and respective obstacles or drawbacks. Our purpose is to contribute to understand why this malignancy presents low responsiveness to current treatments, while overviewing novel ther- apies and clinical trials.
Abstract: Anaplastic thyroidcancer (ATC) is a rare tumour but also one of the most lethal malignancies. Therapeutic modalities have usually been limited, but clinical trials with new drugs are now being implemented. The aims of this study were to analyse the clinical presentation, therapeutic modalities and independent prognostic factors for survival. We also reviewed the most recent literature on novel ATC therapies. We performed a retrospective analysis of 79 patients diagnosed between 2000 and 2018. Variables with impact on survival were identified using the Cox proportional-hazard regression model. At presentation, 6.3% had thyroid-confined disease, 30.4% evidenced extrathyroidal extension and 60.8% were already metastatic. Surgery was feasible in 41.8% and radiotherapy was applied to 35.4%, with those receiving >45 Gy having longer estimated survival (p = 0.020). Chemotherapy, either conventional or with tyrosine kinase inhibitors, was performed in 17.7% and 7.6%, respectively. Multimodality therapy with surgery, radiotherapy and chemotherapy/tyrosine kinase inhibitors (TKI) had the greatest impact on disease specific survival (DSS), providing a risk reduction of death of 96.9% (hazard ratio (HR) = 0.031, 0.005–0.210, p < 0.001). We concluded that most of these patients join reference centres at advanced stages of disease and multimodality treatment may offer the best chances for prolonging survival.
6.5 years). Moreover, we did not do an active screening of other cancers, considering the retrospective nature of the study, such a procedure impractical to monitor all patients with differentiated thyroidcancer, which would burden our health system. Nevertheless, our findings, as previously described in other studies, can suggest that, at least in certain populations, the occurrence of another malignancy after 131 I
Results: 128 (23.5%) of 543 cases male and 415 (76.5%) were female. The youngest patient was 10, the oldest pa- tient was 89 years-old, and the average age is 48.1±15.2. Histopathological examination of 346 (64%) cases of nod- ular hyperplasia, 20 (4%) cases of diffuse hyperplasia, 13 (2.4%) cases of lymphocytic thyroiditis, 164 (30.2%) pa- tient had thyroid tumors. The 164 tumors on the 57 (35%) cases benign, 107 (65%) cases were malign. As a type of cancer 88 (53.6%) cases papillary carcinoma, 10 (6%) cases follicular carcinoma, 1 (0.6%) case medullary carci- noma, 3 (1.8%) cases were anaplastic carcinoma. Conclusion: Thyroidcancer incidence is 19.7% at thy- roidectomy materials in the city of Malatya and most can- cers is seen as a type of thyroid papillary carcinoma. Key words: Goitre, thyroidcancer, papillary carcinoma ÖZET
A study evaluating mortality in Belgrade, Serbia, found the opposite result. It was shown that the av- erage percentage of deaths from thyroidcancer in all deaths was almost twice as high in females (0.11%) than in men (0.6%), and among deaths from all malignant cancers (women and men 0.54% and 0.27%, respective- ly). During this 20 year period, the average standard- ized mortality was 1.5 times higher in females (0.74 per 100,000) than in men (0.51 per 100,000). During the study period, the mortality rates increased for thyroidcancer (0.40%) and decreased in women (-0.42%) in men. In particular, in the age group of 60-69 years, in males, a signiicant trend towards decreased mortality of 3.5% / year was detected (39).
Thyroid carcinoma is the most common endocrine malignancy. Approxi- mately 90% of non-medullary thyroid malignancies are classified as well- differentiated thyroid carcinomas. Even though this type of tumor is not aggressive and usually curable after therapy, recurrence develops in 20- 40% and progression to cellular de-differentiation occurs in up to 30% of patients. Poorly differentiated cancers are characterized by loss of thyroid- specific functions and properties, such as the capacity to concentrate radioiodide. Therapeutic options for de-differentiated thyroidcancer are limited and generally not efficient. Recent studies with retinoic acid (RA) have shown that this drug can induce re-differentiation of the thyrocyte in vitro, as suggested by increased expression of thyroglobulin, type I iodothy- ronine 5’-deiodinase and the sodium/iodide symporter, and by the incre- ment of cellular iodide uptake. Clinical research demonstrated beneficial effects of RA, with 40% of patients with radioiodine non-responsive tumor showing increase of iodide uptake and 20% tumor regression, after RA treatment. (Arq Bras Endocrinol Metab 2003;47/2:190-197)