Thyroid cytology: The reality before and after the introduction of ultrasound classification systems for thyroid nodules

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"Alfonso" "apellidos" => "Vidal-Casariego" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S253001642200204X?idApp=UINPBA00004N" "url" => "/25300164/0000007000000001/v1_202212240616/S253001642200204X/v1_202212240616/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Thyroid cytology: The reality before and after the introduction of ultrasound classification systems for thyroid nodules" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "39" "paginaFinal" => "47" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Sara Campos Lopes, Bijal Shah, Catarina Eloy" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Sara Campos" "apellidos" => "Lopes" "email" => array:1 [ 0 => "saragclopes@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" 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Porto, Portugal" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Citología tiroidea: la realidad antes y después de la introducción de los sistemas de clasificación de los nódulos tiroideos basados en la ecografía" ] ] "textoCompleto" => "IntroductionThyroid nodules are common, with a prevalence as high as has 68% in some ultrasonography series.<a class="elsevierStyleCrossRefs" href="#bib0135">1,2</a> The incidence of nodular thyroid disease and thyroid cancer grew considerably in the last two decades, mainly due to the widespread use of imaging techniques leading to the detection of thyroid incidentalomas.<a class="elsevierStyleCrossRef" href="#bib0145">3</a> Nevertheless, only a minority of these nodules are malignant (7–15%).<a class="elsevierStyleCrossRef" href="#bib0150">4</a>Thyroid ultrasonography (US) is the gold standard for identifying and evaluating thyroid nodules via imaging.<a class="elsevierStyleCrossRef" href="#bib0150">4</a> US helps to differentiate the nodules that need to be investigated with fine-needle aspiration (FNA) biopsy from the ones that only require surveillance. In order to improve diagnostic accuracy, decrease unwarranted FNA biopsies, and prevent overdiagnosis and overtreatment, several risk stratification systems based on the US features of thyroid nodules have been developed worldwide in the last few years.<a class="elsevierStyleCrossRefs" href="#bib0150">4–9</a> In general, these stratification systems focus on similar ultrasonographic features suggestive of malignancy, namely, hypoechogenicity, ill-defined margins, solid appearance, and the presence of calcifications.<a class="elsevierStyleCrossRef" href="#bib0180">10</a>These updated and commonly used US classification systems include the system proposed in the American Thyroid Association (ATA) guidelines from 2015 (published in January 2016),<a class="elsevierStyleCrossRef" href="#bib0150">4</a> the Thyroid Imaging Reporting and Data System (TIRADS) developed by the European Thyroid Association in 2017 (EU-TIRADS),<a class="elsevierStyleCrossRef" href="#bib0160">6</a> and the TIRADS proposed by the American College of Radiology in 2017 (ACR-TIRADS).<a class="elsevierStyleCrossRef" href="#bib0170">8</a> The impact of introducing these stratification US systems on the thyroid nodules referred for FNA and their cytological results is unknown.The main aim of our study was to compare the patients and thyroid nodules referred to FNA and their cytological result before and after the introduction of these well-established US classification systems.Materials and methodsStudy design and patient selectionA retrospective study was conducted at the Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal. The study included all the patients that underwent US-guided thyroid FNA in this institution from 1st October to 10th November 2015 and from 1st October to 10th November 2021 by the same experienced pathologist (CE). The same pathologist performed the cytology report for all the nodules. The system used for the classification of the cytopathological findings was the Bethesda system.<a class="elsevierStyleCrossRef" href="#bib0185">11</a>IPATIMUP is a reference centre for thyroid FNA with an active contract with the Administração Regional de Saúde do Norte (ARS Norte), where primary care providers can send patients for thyroid FNA biopsy and cytology. It has a pathology laboratory that is double accredited by the College of American Pathologists and by NP EN ISO 15189. The remaining patients are referred to IPATIMUP mainly from private practice, and occasionally from public hospitals after specific situations (consecutive Bethesda category I results and/or technically difficult to perform FNA biopsy). To undergo FNA biopsy, the patient needs to have an US report of the thyroid performed within the previous six months.We collected the most recent data from 2021 and the same corresponding period in 2015 to avoid having confounding factors, such as a bias in referral due to an eventual seasonal variation in seeking medical care that could invalidate possible explanations for differences that could emerge from the statistical analyses between the two samples. The year selected to perform the comparison with 2021 was 2015 since it was the last year before the new ATA guidelines<a class="elsevierStyleCrossRef" href="#bib0150">4</a> were proposed (published in January 2016) and subsequently the EU-TIRADS<a class="elsevierStyleCrossRef" href="#bib0160">6</a> and ACR-TIRADS<a class="elsevierStyleCrossRef" href="#bib0170">8</a> scoring systems.The data for characterizing, and then comparing, the patients and nodules from 2015 and 2021 were obtained from the available clinical information provided both by the US report and by the clinician that referred the patient to the IPATIMUP. The variables collected were: sex, age, number of nodules for which FNA was requested per patient, the nodules’ size, the US classification system used and the number of nodules with US criteria to perform FNA. The latter variable was decided based on the guidelines that were in force at the time.In 2015, we considered that the nodule had indication for FNA if it met the criteria presented in the 2009 ATA guidelines, as they were the ones most widely accepted at the time<a class="elsevierStyleCrossRef" href="#bib0190">12</a> and as other US classification systems with scoring systems, such as TIRADS (Horvath et al., 2009),<a class="elsevierStyleCrossRef" href="#bib0155">5</a> were not commonly used in Portugal. To do this assessment, we only had access to the data provided by the clinician as, at the time, the US report was not added to the patients’ file as it is now in 2021. The most common information given was the nodule size and, sporadically, the echogenicity and the nodule composition (solid, cyst, mixed). There was no reference in any of the patients from 2015 of the use of any US classification system, while in the information given by the clinician in 2021, the EU-TIRADS/ACR-TIRADS/ATA classification was frequently reported. Nevertheless, it is relevant to take into consideration that the clinical information given by the clinicians was scarce both in 2015 and in 2021. However, in 2021, we had access to more data, as we had an US report available for analysis for each patient from the previous six months. This was due to the COVID-19 pandemic. Since the first lockdown in Portugal in 2020, in IPATIMUP, the US reports started being scanned and attached to the clinical file of the patients to prevent additional physical contact. The nodule size and the US classification described in the report were collected and used to assess if the nodule had criteria for FNA. The US reports that did not have any reference to an US classification system were labelled as such and considered “missing data” in terms of whether these nodules had criteria for FNA or not. Additionally, the origin of the referral was collected (primary care providers vs other specialties).As mentioned above, our main aim was to compare the cohort of patients and thyroid nodules referred to FNA and their cytological result from 2015 with the 2021 cohort from the same period. Our secondary aim was to characterize and compare the subset of patients and thyroid nodules with an US classification described in the US report (group 1) with the remaining 2021 cohort (group 2) and with the 2015 cohort. When significant differences between group 1 and 2 were not detected on the comparative analysis, we considered the 2021 cohort as a homogenous cohort for that specific variable and did not describe the comparative analysis of group 1 versus the 2015 cohort.Data analysis and statisticsData were retrieved from the SISPAT® software and were exported to Microsoft Office Excel® 2013. The statistical analysis was conducted on Statistical Package for the Social Sciences (IBM® SPSS Statistics, version 26.0).Categorical variables were presented as absolute value (n) and relative frequency (%) and summarized into tables.To assess the normality of the distribution of the continuous variables of each sample, we performed the Shapiro–Wilk test. If normality was assumed, values were presented as mean±standard deviation. If normality was not assumed, values were presented as median and 25–75th percentile (P25–P75).Pearson's chi-square test was used to assess the associations between categorical variables. Student's t-test was used to compare means among normally distributed variables and the Mann–Whitney U test was used to analyze non-normally distributed variables.A p-value below 0.05 was considered statistically significant.ResultsPopulation characteristicsIn this study, 606 adult patients were included (n=386 in 2015; n=220 in 2021). Within the 2021 cohort, group 1 included n=133 patients (60.5%) and group 2 included n=87 patients (39.5%). The number of patients undergoing FNA at IPATIMUP was higher in 2015 in comparison with 2021 due to the physician's availability to schedule the patients (57.0% more patients in 2015). <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the general characteristics of the population.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>In both years, the majority of patients were females (89.1% vs 85.9%, p=0.243). The average age in 2015 was significantly lower when compared with 2021 (53.4±14.5 years vs 57.8±13.2 years, p<0.001). The main source of referral was primary care providers. This source of referral was significantly more frequent in 2021 than in 2015 (89.1% vs 96.4%; p=0.002).No differences were observed between group 1 and group 2 regarding sex distribution (p=0.138), mean age (p=0.096) and source of referral (p=0.904).Characteristics of the thyroid nodulesA total of 471 nodules in 2015 and 273 nodules in 2021 were analyzed. Within the 2021 cohort, group 1 included 61.2% of the nodules (n=165) and group 2 included 38.8% of the nodules (n=106). These totals included all the nodules undergoing FNA biopsy (n=463 in 2015 and n=263 in 2021), plus the additional n=8 nodules in 2015 and n=10 nodules in 2021 for which FNA was requested but FNA was not performed. The reasons for not performing a biopsy in these 18 nodules were due to their small size (below 10mm), and the fact the nodules did not have suspicious US features and were part of a multinodular disease.The median nodule size in 2015 was 16.0mm (P25–P75: 12.0–22.0mm, ranging between 4mm and 66mm), while median nodule size in 2021 was 17.0mm (P25–P75: 14.0–24.0mm, ranging between 5mm and 84mm). This difference in the size of the nodules was statistically significant (p=0.022), seeming to be mainly due to an increase in nodules 10mm or larger in 2021 (17.0mm vs 19.0mm, respectively, p=0.002). The nodules under 10mm had similar medians (8.0mm vs 8.05mm, p=0.873). When comparing group 1 with the 2015 cohort, identical findings were obtained regarding median nodule size [17mm (P25–P75: 14–24mm) vs 16.0mm (P25–P75: 12–22mm), p=0.016], also due to the nodules larger than one centimetre [20mm (P25–P75: 15–27mm) 17mm (P25–P75 13–22mm), p<0.001], and not the ones under one centimetre in size (8.0mm vs 8.05mm, p=0.873).Regarding the 2021 cohort, no significant differences regarding the median nodule size were detected between group 1 and group 2 [19.0mm (P25–P75: 14.0–26.0mm) vs 16.7mm (P25–P75: 14.0–23.0mm), p=0.326]; however, when dividing the nodules into under 10mm and 10mm or larger, similar results to those previously mentioned were detected. There were no differences regarding the nodules under one centimetre in size (8.0mm vs 9.0mm, p=0.498), but the nodules over one centimetre in size were significantly bigger in group 1 (20mm vs 17mm, p=0.043).At least 3.2% of the nodules were under 10mm in 2015 (n=15), as opposed to in 2021 which was almost double (6.6%; n=18), although this was not a statistically significant result (p=0.155). The size of the nodules was not recorded in 23.1% (n=109) of the nodules in 2015 and in 1.5% (n=4) of the nodules in 2021 (n=3 within group 1 – with an associated US categorization).The median number of nodules for which FNA was requested per patient was one in both 2015 and 2021 (range in 2015: 1–5, range in 2021: 1–4). There was information regarding the number of nodules for which FNA biopsy was specifically requested in 428 nodules in 2015 (90.9%), and 271 nodules in 2021 (99.3%). There was no specific request in n=30 patients from 2015 (7.8%) and in n=2 patients from 2021 (0.9%) that were excluded from this analysis.From the 744 nodules analyzed, there was data available to assess criteria for undergoing FNA in 34.6% of the nodules from 2015 (n=163) and in 60.8% of the nodules from 2021 (n=166). Therefore, the availability of data enabling the criteria for FNA to be assessed was significantly better in 2021 (p<0.001). Within the 2021 cohort, there was also a significant difference between group 1 and group 2 regarding the available information to make this decision (p<0.001); the vast majority of the nodules where we could assess the criteria for FNA were from group 1 (n=163; 98.2%). The median nodules with an indication for FNA biopsy per patient was 1 in both years (range in 2015: 0–3, range in 2021: 0–4). FNA was requested for at least 23.1% (n=63) of all the nodules in 2021, although without US criteria [vs n=158 (33.5%) and n=103 (37.7%) nodules with inclusion criteria, respectively]. In both 2015 and 2021, none of the nodules reported to be under 10mm and for which FNA was requested had criteria for FNA biopsy (n=15 and n=18, respectively).The majority of the patients in both years underwent FNA of a single nodule (81.9% vs 81.8%, p=0.993). Therefore, the median nodules undergoing FNA per patient was one in both years (range in both years: 1–3).US classification systemsNone of the nodules from 2015 had any clinical information referring to the use of any risk stratification system. From the 2021 cohort, 60.5% of the patients had an US report with data regarding an US classification system (61.2% of the nodules; n=167) – group 1. More than one-third of the nodules from 2021 were not categorized using a US classification system (38.8%, n=106). The most frequently used US classification system in the sample from 2021 was the EU-TIRADS (39.2%, n=107) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The majority of the nodules with a US classification were ranked as class 4 (46.5%, n=74) and 3 (35.6%, n=57). None were classified as class 1. Grading by US classification system used is reported on <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. There was a positive and significant correlation between having criteria to undergo FNA and the US classification of the 2021 nodules (p<0.001).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Cytology report<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the distribution of the 726 nodules submitted to FNA, as per the cytology report, according to the Bethesda classification<a class="elsevierStyleCrossRef" href="#bib0185">11</a> (n=463 nodules in 2015; n=263 nodules in 2021). There were no differences in terms of distribution of the Bethesda categories between 2015 and 2021 (p=0.082). The same occurred when performing the analysis separately for the nodules that had criteria for FNA (p=0.185) and the nodules that did not have criteria for FNA (p=0.974). Within the 2021 cohort, there were no differences in the overall distribution of Bethesda categories (p=0.469). When performing the analysis for the nodules without an indication for FNA, no differences were detected (p=0.988). However, when evaluating exclusively nodules with indication for FNA, a significant difference was observed for the Bethesda III category nodules that was not taken into consideration due to the small sample size (n=5; n=5). In line with that, considering this small sample size effect for many of the Bethesda categories apart from Bethesda II in group 1, definite conclusions should not be drawn from comparisons between group 1 and the 2015 cohort for the Bethesda I and III to VI categories. When comparing the median nodule sizes for the Bethesda II category nodules, there were significant differences between groups (17mm vs 19mm, p=0.029).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Regarding the size of the thyroid nodules, when performing the analysis separately for the nodules that were under 10mm and the nodules that were 10mm or larger, there were no differences in terms of Bethesda classification between 2015 and 2021 (p=0.586 and p=0.091, respectively). The most common Bethesda categories in any of these subgroups were Bethesda I and II. However, when comparing the median nodule sizes per Bethesda category, there were significant differences between 2015 and 2021. More specifically, between the Bethesda II and Bethesda III nodules from 2015 and 2021 (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). The sample size of the nodules Bethesda V and VI was small [n=4 (n=1 in 2015, n=3 in 2021) and n=10 (n=9 in 2015, n=1 in 2021), respectively], with a wide range of nodule sizes (range 6.8–74mm and 6.5–22mm, respectively). Within the 2021 cohort, there were no differences between group 1 and group 2 regarding the median size of the nodules per Bethesda category, even when performing the analysis separately for the nodules under 10mm and 10mm or larger (p>0.05). <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> summarizes the distribution of the nodules from 2021 that underwent FNA by US classification system category and the corresponding Bethesda category. In 41.4% of the 2021 nodules undergoing FNA (n=109), the US classification system categorization was not applied.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia>DiscussionIt is crucial to accurately distinguish between benign and malignant nodules, to avoid unnecessary surgical procedures, as well as to alleviate potential patients’ psychological distress and reduce healthcare costs.US is the recommended imaging exam for guiding the initial management of thyroid nodules and several US-based classification systems for risk stratification are currently available.<a class="elsevierStyleCrossRefs" href="#bib0150">4–9</a> These systems allow for a standardized risk-stratification assessment of thyroid nodules, leading to more consistent clinical decisions and better agreement between clinicians.<a class="elsevierStyleCrossRefs" href="#bib0150">4–9,13–16</a> They are intended to reduce the number of nodules with an indication for cytological assessment, and consequently, decrease the workload and costs associated with the workup of nodules that would be either benign or malignancies unlikely to cause harm during the patient's lifespan.<a class="elsevierStyleCrossRefs" href="#bib0200">14,15,17</a> These systems include those used in this study: EU-TIRADS, ACR-TIRADS and ATA.<a class="elsevierStyleCrossRefs" href="#bib0150">4,6,8</a>Our results suggest that a change in the management of thyroid nodules in the North region of Portugal might have happened since the US-based classification systems for thyroid nodules were published.<a class="elsevierStyleCrossRefs" href="#bib0150">4,6,8</a> In comparison with 2015, there was a significant adherence to US classification systems in 2021, with most of the nodules being categorized according to one of these systems (61.2%), mainly with the EU-TIRADS (39.2%) and ACR-TIRADS systems. Although developed by an American society, the ACR-TIRADS was used in 21% of the available US reports. This might be due to its well-validated performance and associated higher specificity in triaging thyroid nodules when compared to the EU-TIRADS.<a class="elsevierStyleCrossRef" href="#bib0205">15</a> The ATA<a class="elsevierStyleCrossRef" href="#bib0150">4</a> classification was rarely used (only described in one US report), possibly due to its pattern-based system, instead of the points-based system of ACR TI-RADS and EU-TIRADS, leading to some nodules not being categorized.Nevertheless, some features of the population and respective nodules submitted to FNA biopsy were similar between 2015 and 2021, namely the sex distribution (mainly females, as expected according to the literature<a class="elsevierStyleCrossRefs" href="#bib0220">18,19</a>), the number of nodules for which FNA was requested per patient, the number of nodules undergoing FNA and the Bethesda classification of the nodules.The most significant differences recorded between the two years were as follows: the patients in 2021 were 4.4 years older than in 2015, the size of the nodules was significantly larger in 2021 than in 2015 mainly due to nodules larger than 10mm, and the percentage of patients referred from primary care providers was higher in 2021 (89.1% vs 96.4%; p=0.002). The differences described here may have been due to at least two potential factors. First, the implementation of the US classification systems potentially allowed for extended surveillance periods, leading to older patients and larger nodules. This last observation is further corroborated by the results obtained by the comparison of group 1 with group 2 and with the 2015 cohort. The nodules categorized with an US system (group 1) were significantly larger, apparently at the cost of the nodules larger than one centimetre (3mm larger in diameter when compared to the nodules from group 2 and the 2015 cohort). On the other hand, it may also represent the impact of the COVID-19 pandemic. It resulted in a delay in access to health care services and the emergence of financial-social difficulties, leading to fewer patients resorting to private practice and a higher referral rate from primary care providers.Comparing the nodule size per Bethesda category, both Bethesda II and III category nodules were significantly larger in 2021 (17mm vs 19mm, p=0.036; 11mm vs 23mm, p=0.043, respectively). Bethesda V and VI nodules should not be compared regarding their dimensions due to the small sample size. The size difference between the Bethesda III nodules (12mm) is clinically relevant, since the performing FNA in larger nodules is usually easier, more successful, and with a higher sensitivity.<a class="elsevierStyleCrossRefs" href="#bib0235">20,21</a> However, it is important to mention that the sample size of the Bethesda III nodules was small. It seems that the US classification systems allow delaying FNA, without aggravating the cytology results when FNA becomes indicated, leading to larger nodules in 2021 undergoing FNA. Even the detected size differences of 1 or 2mm, although not clinically relevant, might be indicative of this positive trend. As the Bethesda IV-VI categories have a small sample size not detecting differences regarding the nodules’ dimensions and Bethesda category distribution, it might be due to the low statistical power associated with small populations. According to <a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3 and 4</a>, we can perceive an apparent tendency towards bigger nodules in 2021 across the six Bethesda categories and a slight change in the distribution of the nodules throughout these categories from 2015 to 2021. Regarding the Bethesda category distribution, we could not make correlations with the US risk stratifying systems, as an US classification system categorization was not applied in 41.4% of the 2021 nodules undergoing FNA. However, the most reported US category was EU-TIRADS 4. We reported n=16 nodules EU-TIRADS 5 and n=5 nodules ACR-TIRADS 5, however they did not correspond to the Bethesda V and VI nodules of the 2021 cohort. As shown in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>, none of these Bethesda V–VI nodules were classified as EU-TIRADS 5 or ACR-TIRADS 5. The majority of the nodules EU-TIRADS 5 and ACR-TIRADS 5 undergoing FNA were Bethesda II. Nonetheless, in n=1 Bethesda V and n=1 Bethesda VI, no US classification system was applied so we cannot exclude they would not be classified as EU-TIRADS 5 or ACR-TIRADS 5. We acknowledge a very low percentage of Bethesda V and VI in our cohorts. Possible explanations for the scarcity of higher risk Bethesda categories might be the high percentage of nodules referred for FNA that did not have criteria for it; the fact that the US were performed by multiple radiologists with different degrees of experience in thyroid US (being the majority non-exclusively dedicated to this type of US). Another important factor to considered is that there is a potential referral bias associated with the IPATIMUP itself, where the majority of the FNAs are requested by primary care providers, as opposed to the hospital setting where they have a higher percentage of referrals from hospital specialties, and nodules diagnosed in more complex contexts. Additionally, some more complicated situations are sent to IPATIMUP from private practice, and occasionally from public hospitals, namely, consecutive Bethesda category I or III and/or technically difficult to perform FNA biopsies. These nodules might not have initially had an indication for FNA. As the low rate of Bethesda V and VI was observed both in 2015 and 2021, a potential referral bias and high percentage of referred nodules without an indication for FNA are the most plausible justifications. A further topic of research in the IPATIMUP will be to assess in a larger population the potential variables responsible for this atypical low percentage of Bethesda V and VI categories in our sample and to have the statistical power to correlate the Bethesda categories with the US classification systems categories.The most recent US-based classification systems<a class="elsevierStyleCrossRefs" href="#bib0150">4,6,8</a> (and the ones included in this study) are more conservative than the guidelines in force in 2015<a class="elsevierStyleCrossRefs" href="#bib0155">5,12</a> regarding nodule size thresholds that indicate cytological assessment. Nodules under one centimetre no longer indicate FNA, even if high-risk factors are present, as the course of papillary microcarcinoma is usually indolent.<a class="elsevierStyleCrossRef" href="#bib0150">4</a> Consequently, this leads to fewer FNA. However, in 2021, nodules under 10mm are still being referred to FNA. At least 6.6% of nodules referred in 2021 were under 10mm, as opposed to 2015 (at least 3.2%). Nevertheless, in 2015 we did not have access to the nodule size in 33.5% of the nodules, and therefore a direct comparison between the two years should be interpreted with caution. Even with several risk-stratification systems available in 2021, nearly 40% of the nodules are still not being stratified with an ultrasound classification system, precluding the clinician to assess indication for FNA in virtually all of those nodules. This goes along the same lines of a recent study reporting inconsistent and incomplete descriptions of thyroid nodules, with some US features only being reported in as few as 9% of the nodules.<a class="elsevierStyleCrossRef" href="#bib0260">22</a> Consequently, nearly all the 2021 nodules where we were able to assess the criteria for FNA were nodules classified with an US risk stratifying system (98.2%), and the n=3 nodules without this categorization that we were able to assess indication for FNA was due to the large dimensions of the nodules (more than 20mm in diameter). Additionally, at least 38% of the nodules referred to FNA in 2021 did not have criteria to do it, testifying that the clinicians do not always follow the recommendations associated with each risk category. This might partly justify why the distribution of the Bethesda categories did not significantly change from 2015 to 2021.The ongoing referral for biopsy of nodules under one centimetre in size and other nodules without indication for cytological assessment also shows us that other factors are accountable for this, independently of these classification systems. We could speculate some contributing factors are the patients’ expectations, as research shows office consults’ satisfaction suffers and health-related anxiety increases when wanted diagnostic interventions are not obtained,<a class="elsevierStyleCrossRefs" href="#bib0245">23,24</a> and, somewhat related, the rise of defensive medicine in Europe.<a class="elsevierStyleCrossRef" href="#bib0255">25</a>It is pertinent to mention two important caveats concerning our data. We had a significant percentage of missing data regarding nodule size in 2015 (33.5% of the nodules) and regarding information on US criteria to undergo FNA in both 2015 and 2021 (65.4% vs 39.2%, respectively). To assess the indication for FNA of these nodules in 2015, we had to use that limited data (mainly, the nodule size), leading to a potential information bias without taking into consideration potential specific risk factors such as a history of thyroid cancer in first degree relatives, history of external beam radiation as a child, previous hemithyroidectomy with discovery of thyroid cancer, and 18FDG avidity on PET scans.<a class="elsevierStyleCrossRef" href="#bib0190">12</a> These factors are no longer considered in the updated systems,<a class="elsevierStyleCrossRefs" href="#bib0150">4,6,8</a> facilitating their application. This study includes other limitations. Thyroid US was performed by multiple radiologists introducing operator-driven variability that was not controllable. However, we can contemplate this as a strength of the study since the wide diversity of examiners with different levels of expertise performing the US led to a sample more representative of what is happening in daily clinical practice. Another limitation was the retrospective design of this study, leading to gaps in information. The higher number of patients who underwent FNA in 2015 (57% more patients) was due to institutional constraints associated with the availability of the pathologist performing this technique in the previous months, leading to a bigger waitlist in October 2015.ConclusionThis study is the first study to compare the reality in Portugal of thyroid FNA and cytology before and after the publication of the most commonly used US-based classification systems for thyroid nodules. To the best of our knowledge, it is also the first published study worldwide making this comparison and assessment. This analysis draws attention to the importance of systematically applying US-based classification systems for thyroid nodules in our daily clinical practice. It seems that these systems, by not being focused mainly on size thresholds, allow for extended surveillance periods, without aggravating the cytology results when FNA becomes indicated. FNA potentially become safer as the nodules are permitted to have larger dimensions. Nevertheless, bigger efforts are needed to ensure more standardized US reports by systematically using these risk-stratification systems and, when applied, to increase adherence to the resulting recommendations. This will allow more consistent clinical decisions, with a decrease in clinical uncertainty, unnecessary FNA biopsies, and potential overtreatment.Ethical considerationsAll procedures were in accordance with the ethical standards of the institutional ethics committee and in line with the principles of the Declaration of Helsinki.Funding sourcesThis research did not receive any specific grant from funding agencies.Conflict of interestNo conflicts of interest in connection with this article." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1824625" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1591471" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1824624" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1591472" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design and patient selection" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Data analysis and statistics" ] ] ] 6 => array:3 [ "identificador" => "sec0025" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Population characteristics" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Characteristics of the thyroid nodules" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "US classification systems" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Cytology report" ] ] ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Ethical considerations" ] 10 => array:2 [ "identificador" => "sec0065" "titulo" => "Funding sources" ] 11 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "xack643671" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-04-12" "fechaAceptado" => "2022-06-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1591471" "palabras" => array:4 [ 0 => "Thyroid nodule" 1 => "Fine-needle" 2 => "Biopsy" 3 => "Ultrasonography" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1591472" "palabras" => array:4 [ 0 => "Nódulo tiroideo" 1 => "Aguja fina" 2 => "Biopsia" 3 => "Ultrasonografía" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundSeveral ultrasound-based systems for classification of thyroid nodules are available. They allow for a better triage of the nodules that require cytological assessment, and lead to standardized recommendations. Our aim was to compare patients and nodules referred to fine-needle aspiration (FNA) before and after the introduction of these systems. MethodsA retrospective study comparing two cohorts of patients referred for FNA was performed (386 patients and 463 nodules in 2015; 220 patients and 263 nodules in 2021). ResultsThe sex distribution (89.1% vs 85.9% females, p=0.243), number of nodules referred to FNA per patient (median of 1), and the distribution of the Bethesda categories (p=0.082) was similar in both years. In 2021, patients were older (53.4±14.5 years vs 57.8±13.2 years, p<0.001) and nodules over one centimetre were larger (median 17.0mm vs 19.0mm, p=0.002), especially the ones categorized as Bethesda III (median size 11mm vs 23mm, p=0.043). In 2021, at least 23.1% of the nodules referred to FNA did not have any criteria, and 38.8% of the nodules were not categorized by any system. ConclusionThis analysis draws attention to the importance of systematically applying ultrasound-based classification systems. It seems that, by not being focused mainly on size thresholds, they allow for longer surveillance periods, without aggravating the cytology results when FNA becomes indicated. Nevertheless, greater efforts are needed to ensure more standardized reports, and to increase adherence to the resulting recommendations to reduce clinical uncertainty, unnecessary FNA, and overtreatment." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "AntecedentesExisten varios sistemas basados en la ecografía para la clasificación de los nódulos tiroideos. Permiten un mejor triaje de los nódulos que requieren una evaluación citológica y conducen a recomendaciones estandarizadas. Nuestro objetivo fue comparar los pacientes y los nódulos remitidos para punción aspiración con aguja fina (PAAF) antes y después de la introducción de estos sistemas. MétodosSe realizó un estudio retrospectivo comparando 2 cohortes de pacientes remitidos para PAAF (386 pacientes y 463 nódulos en 2015; 220 pacientes y 263 nódulos en 2021). ResultadosLa distribución por género (89,1% vs. 85,9% mujeres, p=0,243), el número de nódulos remitidos para PAAF por paciente (mediana: 1) y la distribución de las categorías Bethesda (p=0,082) fue similar en ambos años. En 2021 los pacientes eran de mayor edad (53,4±14,5años vs. 57,8±13,2años, p<0,001) y los nódulos supracentimétricos eran mayores (mediana 17,0mm vs. 19,0mm, p=0,002), especialmente los Bethesda III (mediana 11mm vs. 23mm, p=0,043). En 2021 al menos el 23,1% de los nódulos remitidos a PAAF no tenían criterios, y el 38,8% de los nódulos no fueron categorizados por ningún sistema. ConclusiónEste análisis llama la atención sobre la importancia de aplicar este sistemas de clasificación. Parece que, al no estar centrados principalmente en el tamaño, permiten períodos de vigilancia más prolongados, sin agravar la citología cuando se indica la PAAF. No obstante, es necesario realizar mayores esfuerzos para garantizar informes más estandarizados y aumentar la adherencia a las recomendaciones resultantes, con el fin de reducir la incertidumbre clínica y las PAAF innecesarias." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "FNA, fine needle aspiration; SD, standard deviation." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">2015 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">2021 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=386 patients) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n=220 patients) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gender, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 (10.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (14.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.243 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">344 (89.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">189 (85.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years), mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.4±14.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.8±13.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Source of referral, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Primary care provider \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">344 (89.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">212 (96.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other specialties \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 (10.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (3.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients submitted to FNA, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 nodule \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">316 (81.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">180 (81.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.993 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 nodules \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63 (16.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (16.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 nodules \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (1.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "General characteristics of the patients from 2015 and from 2021." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ACR, American College of Radiology; ATA, American Thyroid Association; EU, European; NA, not applicable; TIRADS, Thyroid Imaging Reporting and Data System; US, ultrasound." "tablatextoimagen" => array:2 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">US classification system used n (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">EU-TIRADS \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ACR-TIRADS \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ATA \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Not referred \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">107 (39.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (21.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (0.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">106 (38.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] 1 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">US classification system category \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">EU-TIRADS (n=107) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ACR-TIRADS (n=58) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ATA (n=2) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Not known (n=106) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Class 1, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Class 2, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (2.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (5.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Class 3, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (27.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (46.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Class 4, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (48.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (37.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Class 5, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (15.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (8.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not referred, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (6.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">106 (100) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Distribution of the 273 nodules from 2021 as per the US classification system used and corresponding category." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AUS/FLUS: Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Bethesda classification \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">2015 (n=463) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2021 (n=263)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group 1 (n=102) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group 2 (n=161) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">I – Non diagnostic, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (12.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (9.1)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (29.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (70.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">II – Benign, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">366 (79.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">215 (81.7)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87 (40.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">128 (59.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">III – AUS/FLUS, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (3.8)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (50) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IV – Follicular tumour, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (4.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (3.8)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (70) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V – Suspicious for malignancy, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (0.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (1.1)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (100) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VI – Malignant, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (0.4)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (100) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Distribution of the nodules undergoing FNA, according to the Bethesda classification." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AUS/FLUS: Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bethesda classification \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2015 (n=463) median size, mm \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2021 (n=263) median size, mm \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">I – Non diagnostic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.642 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">II – Benign \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.036 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">III – AUS/FLUS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.043 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IV – Follicular tumour \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.352 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V – Suspicious for malignancy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.655 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VI – Malignant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.377 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison of the median nodule size per Bethesda category between 2015 and 2021." ] ] 4 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ACR, American College of Radiology; ATA, American Thyroid Association; EU, European; NA, Not applicable; TIRADS, Thyroid Imaging Reporting and Data System; US, Ultrasound." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="6" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bethesda classification</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">US classification system category \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bethesda In (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bethesda IIn (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bethesda IIIn (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bethesda IVn (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bethesda Vn (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bethesda VIn (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EU-TIRADS 2 (n=3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (1.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EU-TIRADS 3 (n=29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (11.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EU-TIRADS 4 (n=52) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (20.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 (19.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EU-TIRADS 5 (n=16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (6.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACR-TIRADS 2 (n=2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (0.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACR-TIRADS 3 (n=26) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (12.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (9.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACR-TIRADS 4 (n=21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (12.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (7.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACR-TIRADS 5 (n=4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (0.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ATA 3 (n=1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (0.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown (n=109) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (29.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">91 (42.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (100) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TOTAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">215 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (100) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Distribution of the nodules from 2021 undergoing FNA, as per their US classification system category and Bethesda classification (n=263)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:25 [ 0 => array:3 [ "identificador" => "bib0135" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Very high prevalence of thyroid nodules detected by high frequency (13MHz) ultrasound examination" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. 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Original article

Thyroid cytology: The reality before and after the introduction of ultrasound classification systems for thyroid nodules

Citología tiroidea: la realidad antes y después de la introducción de los sistemas de clasificación de los nódulos tiroideos basados en la ecografía

Sara Campos Lopesa,

Corresponding author

saragclopes@gmail.com

Corresponding author.

, Bijal Shahb, Catarina Eloyc,d

a Endocrinology Department, Hospital de Braga, Braga, Portugal

b Histopathology Department, St. James's Hospital, Dublin, Ireland

c Pathology Laboratory, Institute of Molecular Pathology and Immunology of University of Porto, Porto, Portugal

d Pathology Department of Medical Faculty, University of Porto, Porto, Portugal

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Thyroid nodules are common&#44; with a prevalence as high as has 68&#37; in some ultrasonography series&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">1&#44;2</span></a> The incidence of nodular thyroid disease and thyroid cancer grew considerably in the last two decades&#44; mainly due to the widespread use of imaging techniques leading to the detection of thyroid incidentalomas&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a> Nevertheless&#44; only a minority of these nodules are malignant &#40;7&#8211;15&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Thyroid ultrasonography &#40;US&#41; is the gold standard for identifying and evaluating thyroid nodules via imaging&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> US helps to differentiate the nodules that need to be investigated with fine-needle aspiration &#40;FNA&#41; biopsy from the ones that only require surveillance&#46; In order to improve diagnostic accuracy&#44; decrease unwarranted FNA biopsies&#44; and prevent overdiagnosis and overtreatment&#44; several risk stratification systems based on the US features of thyroid nodules have been developed worldwide in the last few years&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#8211;9</span></a> In general&#44; these stratification systems focus on similar ultrasonographic features suggestive of malignancy&#44; namely&#44; hypoechogenicity&#44; ill-defined margins&#44; solid appearance&#44; and the presence of calcifications&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">These updated and commonly used US classification systems include the system proposed in the American Thyroid Association &#40;ATA&#41; guidelines from 2015 &#40;published in January 2016&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> the Thyroid Imaging Reporting and Data System &#40;TIRADS&#41; developed by the European Thyroid Association in 2017 &#40;EU-TIRADS&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">6</span></a> and the TIRADS proposed by the American College of Radiology in 2017 &#40;ACR-TIRADS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a> The impact of introducing these stratification US systems on the thyroid nodules referred for FNA and their cytological results is unknown&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The main aim of our study was to compare the patients and thyroid nodules referred to FNA and their cytological result before and after the introduction of these well-established US classification systems&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design and patient selection</span><p id="par0025" class="elsevierStylePara elsevierViewall">A retrospective study was conducted at the Institute of Molecular Pathology and Immunology of the University of Porto &#40;IPATIMUP&#41;&#44; Porto&#44; Portugal&#46; The study included all the patients that underwent US-guided thyroid FNA in this institution from 1st October to 10th November 2015 and from 1st October to 10th November 2021 by the same experienced pathologist &#40;CE&#41;&#46; The same pathologist performed the cytology report for all the nodules&#46; The system used for the classification of the cytopathological findings was the Bethesda system&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">IPATIMUP is a reference centre for thyroid FNA with an active contract with the Administra&#231;&#227;o Regional de Sa&#250;de do Norte &#40;ARS Norte&#41;&#44; where primary care providers can send patients for thyroid FNA biopsy and cytology&#46; It has a pathology laboratory that is double accredited by the College of American Pathologists and by NP EN ISO 15189&#46; The remaining patients are referred to IPATIMUP mainly from private practice&#44; and occasionally from public hospitals after specific situations &#40;consecutive Bethesda category I results and&#47;or technically difficult to perform FNA biopsy&#41;&#46; To undergo FNA biopsy&#44; the patient needs to have an US report of the thyroid performed within the previous six months&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We collected the most recent data from 2021 and the same corresponding period in 2015 to avoid having confounding factors&#44; such as a bias in referral due to an eventual seasonal variation in seeking medical care that could invalidate possible explanations for differences that could emerge from the statistical analyses between the two samples&#46; The year selected to perform the comparison with 2021 was 2015 since it was the last year before the new ATA guidelines<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> were proposed &#40;published in January 2016&#41; and subsequently the EU-TIRADS<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">6</span></a> and ACR-TIRADS<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a> scoring systems&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The data for characterizing&#44; and then comparing&#44; the patients and nodules from 2015 and 2021 were obtained from the available clinical information provided both by the US report and by the clinician that referred the patient to the IPATIMUP&#46; The variables collected were&#58; sex&#44; age&#44; number of nodules for which FNA was requested per patient&#44; the nodules&#8217; size&#44; the US classification system used and the number of nodules with US criteria to perform FNA&#46; The latter variable was decided based on the guidelines that were in force at the time&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In 2015&#44; we considered that the nodule had indication for FNA if it met the criteria presented in the 2009 ATA guidelines&#44; as they were the ones most widely accepted at the time<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> and as other US classification systems with scoring systems&#44; such as TIRADS &#40;Horvath et al&#46;&#44; 2009&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> were not commonly used in Portugal&#46; To do this assessment&#44; we only had access to the data provided by the clinician as&#44; at the time&#44; the US report was not added to the patients&#8217; file as it is now in 2021&#46; The most common information given was the nodule size and&#44; sporadically&#44; the echogenicity and the nodule composition &#40;solid&#44; cyst&#44; mixed&#41;&#46; There was no reference in any of the patients from 2015 of the use of any US classification system&#44; while in the information given by the clinician in 2021&#44; the EU-TIRADS&#47;ACR-TIRADS&#47;ATA classification was frequently reported&#46; Nevertheless&#44; it is relevant to take into consideration that the clinical information given by the clinicians was scarce both in 2015 and in 2021&#46; However&#44; in 2021&#44; we had access to more data&#44; as we had an US report available for analysis for each patient from the previous six months&#46; This was due to the COVID-19 pandemic&#46; Since the first lockdown in Portugal in 2020&#44; in IPATIMUP&#44; the US reports started being scanned and attached to the clinical file of the patients to prevent additional physical contact&#46; The nodule size and the US classification described in the report were collected and used to assess if the nodule had criteria for FNA&#46; The US reports that did not have any reference to an US classification system were labelled as such and considered &#8220;missing data&#8221; in terms of whether these nodules had criteria for FNA or not&#46; Additionally&#44; the origin of the referral was collected &#40;primary care providers vs other specialties&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">As mentioned above&#44; our main aim was to compare the cohort of patients and thyroid nodules referred to FNA and their cytological result from 2015 with the 2021 cohort from the same period&#46; Our secondary aim was to characterize and compare the subset of patients and thyroid nodules with an US classification described in the US report &#40;group 1&#41; with the remaining 2021 cohort &#40;group 2&#41; and with the 2015 cohort&#46; When significant differences between group 1 and 2 were not detected on the comparative analysis&#44; we considered the 2021 cohort as a homogenous cohort for that specific variable and did not describe the comparative analysis of group 1 versus the 2015 cohort&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Data analysis and statistics</span><p id="par0055" class="elsevierStylePara elsevierViewall">Data were retrieved from the SISPAT&#174; software and were exported to Microsoft Office Excel&#174; 2013&#46; The statistical analysis was conducted on Statistical Package for the Social Sciences &#40;IBM&#174; SPSS Statistics&#44; version 26&#46;0&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Categorical variables were presented as absolute value &#40;<span class="elsevierStyleItalic">n</span>&#41; and relative frequency &#40;&#37;&#41; and summarized into tables&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">To assess the normality of the distribution of the continuous variables of each sample&#44; we performed the Shapiro&#8211;Wilk test&#46; If normality was assumed&#44; values were presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46; If normality was not assumed&#44; values were presented as median and 25&#8211;75th percentile &#40;P25&#8211;P75&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Pearson&#39;s chi-square test was used to assess the associations between categorical variables&#46; Student&#39;s <span class="elsevierStyleItalic">t</span>-test was used to compare means among normally distributed variables and the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test was used to analyze non-normally distributed variables&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">A <span class="elsevierStyleItalic">p</span>-value below 0&#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Population characteristics</span><p id="par0080" class="elsevierStylePara elsevierViewall">In this study&#44; 606 adult patients were included &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>386 in 2015&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>220 in 2021&#41;&#46; Within the 2021 cohort&#44; group 1 included <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>133 patients &#40;60&#46;5&#37;&#41; and group 2 included <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>87 patients &#40;39&#46;5&#37;&#41;&#46; The number of patients undergoing FNA at IPATIMUP was higher in 2015 in comparison with 2021 due to the physician&#39;s availability to schedule the patients &#40;57&#46;0&#37; more patients in 2015&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the general characteristics of the population&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">In both years&#44; the majority of patients were females &#40;89&#46;1&#37; vs 85&#46;9&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;243&#41;&#46; The average age in 2015 was significantly lower when compared with 2021 &#40;53&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;5 years vs 57&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;2 years&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The main source of referral was primary care providers&#46; This source of referral was significantly more frequent in 2021 than in 2015 &#40;89&#46;1&#37; vs 96&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">No differences were observed between group 1 and group 2 regarding sex distribution &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;138&#41;&#44; mean age &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;096&#41; and source of referral &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;904&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Characteristics of the thyroid nodules</span><p id="par0095" class="elsevierStylePara elsevierViewall">A total of 471 nodules in 2015 and 273 nodules in 2021 were analyzed&#46; Within the 2021 cohort&#44; group 1 included 61&#46;2&#37; of the nodules &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>165&#41; and group 2 included 38&#46;8&#37; of the nodules &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>106&#41;&#46; These totals included all the nodules undergoing FNA biopsy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>463 in 2015 and <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>263 in 2021&#41;&#44; plus the additional <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8 nodules in 2015 and <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10 nodules in 2021 for which FNA was requested but FNA was not performed&#46; The reasons for not performing a biopsy in these 18 nodules were due to their small size &#40;below 10<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; and the fact the nodules did not have suspicious US features and were part of a multinodular disease&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The median nodule size in 2015 was 16&#46;0<span class="elsevierStyleHsp" style=""></span>mm &#40;P25&#8211;P75&#58; 12&#46;0&#8211;22&#46;0<span class="elsevierStyleHsp" style=""></span>mm&#44; ranging between 4<span class="elsevierStyleHsp" style=""></span>mm and 66<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; while median nodule size in 2021 was 17&#46;0<span class="elsevierStyleHsp" style=""></span>mm &#40;P25&#8211;P75&#58; 14&#46;0&#8211;24&#46;0<span class="elsevierStyleHsp" style=""></span>mm&#44; ranging between 5<span class="elsevierStyleHsp" style=""></span>mm and 84<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; This difference in the size of the nodules was statistically significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;022&#41;&#44; seeming to be mainly due to an increase in nodules 10<span class="elsevierStyleHsp" style=""></span>mm or larger in 2021 &#40;17&#46;0<span class="elsevierStyleHsp" style=""></span>mm vs 19&#46;0<span class="elsevierStyleHsp" style=""></span>mm&#44; respectively&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46; The nodules under 10<span class="elsevierStyleHsp" style=""></span>mm had similar medians &#40;8&#46;0<span class="elsevierStyleHsp" style=""></span>mm vs 8&#46;05<span class="elsevierStyleHsp" style=""></span>mm&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;873&#41;&#46; When comparing group 1 with the 2015 cohort&#44; identical findings were obtained regarding median nodule size &#91;17<span class="elsevierStyleHsp" style=""></span>mm &#40;P25&#8211;P75&#58; 14&#8211;24<span class="elsevierStyleHsp" style=""></span>mm&#41; vs 16&#46;0<span class="elsevierStyleHsp" style=""></span>mm &#40;P25&#8211;P75&#58; 12&#8211;22<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;016&#93;&#44; also due to the nodules larger than one centimetre &#91;20<span class="elsevierStyleHsp" style=""></span>mm &#40;P25&#8211;P75&#58; 15&#8211;27<span class="elsevierStyleHsp" style=""></span>mm&#41; 17<span class="elsevierStyleHsp" style=""></span>mm &#40;P25&#8211;P75 13&#8211;22<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#93;&#44; and not the ones under one centimetre in size &#40;8&#46;0<span class="elsevierStyleHsp" style=""></span>mm vs 8&#46;05<span class="elsevierStyleHsp" style=""></span>mm&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;873&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Regarding the 2021 cohort&#44; no significant differences regarding the median nodule size were detected between group 1 and group 2 &#91;19&#46;0<span class="elsevierStyleHsp" style=""></span>mm &#40;P25&#8211;P75&#58; 14&#46;0&#8211;26&#46;0<span class="elsevierStyleHsp" style=""></span>mm&#41; vs 16&#46;7<span class="elsevierStyleHsp" style=""></span>mm &#40;P25&#8211;P75&#58; 14&#46;0&#8211;23&#46;0<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;326&#93;&#59; however&#44; when dividing the nodules into under 10<span class="elsevierStyleHsp" style=""></span>mm and 10<span class="elsevierStyleHsp" style=""></span>mm or larger&#44; similar results to those previously mentioned were detected&#46; There were no differences regarding the nodules under one centimetre in size &#40;8&#46;0<span class="elsevierStyleHsp" style=""></span>mm vs 9&#46;0<span class="elsevierStyleHsp" style=""></span>mm&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;498&#41;&#44; but the nodules over one centimetre in size were significantly bigger in group 1 &#40;20<span class="elsevierStyleHsp" style=""></span>mm vs 17<span class="elsevierStyleHsp" style=""></span>mm&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;043&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">At least 3&#46;2&#37; of the nodules were under 10<span class="elsevierStyleHsp" style=""></span>mm in 2015 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#41;&#44; as opposed to in 2021 which was almost double &#40;6&#46;6&#37;&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18&#41;&#44; although this was not a statistically significant result &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;155&#41;&#46; The size of the nodules was not recorded in 23&#46;1&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>109&#41; of the nodules in 2015 and in 1&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41; of the nodules in 2021 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3 within group 1 &#8211; with an associated US categorization&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The median number of nodules for which FNA was requested per patient was one in both 2015 and 2021 &#40;range in 2015&#58; 1&#8211;5&#44; range in 2021&#58; 1&#8211;4&#41;&#46; There was information regarding the number of nodules for which FNA biopsy was specifically requested in 428 nodules in 2015 &#40;90&#46;9&#37;&#41;&#44; and 271 nodules in 2021 &#40;99&#46;3&#37;&#41;&#46; There was no specific request in <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30 patients from 2015 &#40;7&#46;8&#37;&#41; and in <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2 patients from 2021 &#40;0&#46;9&#37;&#41; that were excluded from this analysis&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">From the 744 nodules analyzed&#44; there was data available to assess criteria for undergoing FNA in 34&#46;6&#37; of the nodules from 2015 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>163&#41; and in 60&#46;8&#37; of the nodules from 2021 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>166&#41;&#46; Therefore&#44; the availability of data enabling the criteria for FNA to be assessed was significantly better in 2021 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Within the 2021 cohort&#44; there was also a significant difference between group 1 and group 2 regarding the available information to make this decision &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#59; the vast majority of the nodules where we could assess the criteria for FNA were from group 1 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>163&#59; 98&#46;2&#37;&#41;&#46; The median nodules with an indication for FNA biopsy per patient was 1 in both years &#40;range in 2015&#58; 0&#8211;3&#44; range in 2021&#58; 0&#8211;4&#41;&#46; FNA was requested for at least 23&#46;1&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>63&#41; of all the nodules in 2021&#44; although without US criteria &#91;vs <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>158 &#40;33&#46;5&#37;&#41; and <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>103 &#40;37&#46;7&#37;&#41; nodules with inclusion criteria&#44; respectively&#93;&#46; In both 2015 and 2021&#44; none of the nodules reported to be under 10<span class="elsevierStyleHsp" style=""></span>mm and for which FNA was requested had criteria for FNA biopsy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15 and <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18&#44; respectively&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The majority of the patients in both years underwent FNA of a single nodule &#40;81&#46;9&#37; vs 81&#46;8&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;993&#41;&#46; Therefore&#44; the median nodules undergoing FNA per patient was one in both years &#40;range in both years&#58; 1&#8211;3&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">US classification systems</span><p id="par0130" class="elsevierStylePara elsevierViewall">None of the nodules from 2015 had any clinical information referring to the use of any risk stratification system&#46; From the 2021 cohort&#44; 60&#46;5&#37; of the patients had an US report with data regarding an US classification system &#40;61&#46;2&#37; of the nodules&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>167&#41; &#8211; group 1&#46; More than one-third of the nodules from 2021 were not categorized using a US classification system &#40;38&#46;8&#37;&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>106&#41;&#46; The most frequently used US classification system in the sample from 2021 was the EU-TIRADS &#40;39&#46;2&#37;&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>107&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The majority of the nodules with a US classification were ranked as class 4 &#40;46&#46;5&#37;&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>74&#41; and 3 &#40;35&#46;6&#37;&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>57&#41;&#46; None were classified as class 1&#46; Grading by US classification system used is reported on <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; There was a positive and significant correlation between having criteria to undergo FNA and the US classification of the 2021 nodules &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Cytology report</span><p id="par0135" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the distribution of the 726 nodules submitted to FNA&#44; as per the cytology report&#44; according to the Bethesda classification<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a> &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>463 nodules in 2015&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>263 nodules in 2021&#41;&#46; There were no differences in terms of distribution of the Bethesda categories between 2015 and 2021 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;082&#41;&#46; The same occurred when performing the analysis separately for the nodules that had criteria for FNA &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;185&#41; and the nodules that did not have criteria for FNA &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;974&#41;&#46; Within the 2021 cohort&#44; there were no differences in the overall distribution of Bethesda categories &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;469&#41;&#46; When performing the analysis for the nodules without an indication for FNA&#44; no differences were detected &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;988&#41;&#46; However&#44; when evaluating exclusively nodules with indication for FNA&#44; a significant difference was observed for the Bethesda III category nodules that was not taken into consideration due to the small sample size &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&#46; In line with that&#44; considering this small sample size effect for many of the Bethesda categories apart from Bethesda II in group 1&#44; definite conclusions should not be drawn from comparisons between group 1 and the 2015 cohort for the Bethesda I and III to VI categories&#46; When comparing the median nodule sizes for the Bethesda II category nodules&#44; there were significant differences between groups &#40;17<span class="elsevierStyleHsp" style=""></span>mm vs 19<span class="elsevierStyleHsp" style=""></span>mm&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;029&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Regarding the size of the thyroid nodules&#44; when performing the analysis separately for the nodules that were under 10<span class="elsevierStyleHsp" style=""></span>mm and the nodules that were 10<span class="elsevierStyleHsp" style=""></span>mm or larger&#44; there were no differences in terms of Bethesda classification between 2015 and 2021 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;586 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;091&#44; respectively&#41;&#46; The most common Bethesda categories in any of these subgroups were Bethesda I and II&#46; However&#44; when comparing the median nodule sizes per Bethesda category&#44; there were significant differences between 2015 and 2021&#46; More specifically&#44; between the Bethesda II and Bethesda III nodules from 2015 and 2021 &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; The sample size of the nodules Bethesda V and VI was small &#91;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1 in 2015&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3 in 2021&#41; and <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9 in 2015&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1 in 2021&#41;&#44; respectively&#93;&#44; with a wide range of nodule sizes &#40;range 6&#46;8&#8211;74<span class="elsevierStyleHsp" style=""></span>mm and 6&#46;5&#8211;22<span class="elsevierStyleHsp" style=""></span>mm&#44; respectively&#41;&#46; Within the 2021 cohort&#44; there were no differences between group 1 and group 2 regarding the median size of the nodules per Bethesda category&#44; even when performing the analysis separately for the nodules under 10<span class="elsevierStyleHsp" style=""></span>mm and 10<span class="elsevierStyleHsp" style=""></span>mm or larger &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> summarizes the distribution of the nodules from 2021 that underwent FNA by US classification system category and the corresponding Bethesda category&#46; In 41&#46;4&#37; of the 2021 nodules undergoing FNA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>109&#41;&#44; the US classification system categorization was not applied&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0145" class="elsevierStylePara elsevierViewall">It is crucial to accurately distinguish between benign and malignant nodules&#44; to avoid unnecessary surgical procedures&#44; as well as to alleviate potential patients&#8217; psychological distress and reduce healthcare costs&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">US is the recommended imaging exam for guiding the initial management of thyroid nodules and several US-based classification systems for risk stratification are currently available&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#8211;9</span></a> These systems allow for a standardized risk-stratification assessment of thyroid nodules&#44; leading to more consistent clinical decisions and better agreement between clinicians&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#8211;9&#44;13&#8211;16</span></a> They are intended to reduce the number of nodules with an indication for cytological assessment&#44; and consequently&#44; decrease the workload and costs associated with the workup of nodules that would be either benign or malignancies unlikely to cause harm during the patient&#39;s lifespan&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">14&#44;15&#44;17</span></a> These systems include those used in this study&#58; EU-TIRADS&#44; ACR-TIRADS and ATA&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#44;6&#44;8</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Our results suggest that a change in the management of thyroid nodules in the North region of Portugal might have happened since the US-based classification systems for thyroid nodules were published&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#44;6&#44;8</span></a> In comparison with 2015&#44; there was a significant adherence to US classification systems in 2021&#44; with most of the nodules being categorized according to one of these systems &#40;61&#46;2&#37;&#41;&#44; mainly with the EU-TIRADS &#40;39&#46;2&#37;&#41; and ACR-TIRADS systems&#46; Although developed by an American society&#44; the ACR-TIRADS was used in 21&#37; of the available US reports&#46; This might be due to its well-validated performance and associated higher specificity in triaging thyroid nodules when compared to the EU-TIRADS&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a> The ATA<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> classification was rarely used &#40;only described in one US report&#41;&#44; possibly due to its pattern-based system&#44; instead of the points-based system of ACR TI-RADS and EU-TIRADS&#44; leading to some nodules not being categorized&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Nevertheless&#44; some features of the population and respective nodules submitted to FNA biopsy were similar between 2015 and 2021&#44; namely the sex distribution &#40;mainly females&#44; as expected according to the literature<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">18&#44;19</span></a>&#41;&#44; the number of nodules for which FNA was requested per patient&#44; the number of nodules undergoing FNA and the Bethesda classification of the nodules&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The most significant differences recorded between the two years were as follows&#58; the patients in 2021 were 4&#46;4 years older than in 2015&#44; the size of the nodules was significantly larger in 2021 than in 2015 mainly due to nodules larger than 10<span class="elsevierStyleHsp" style=""></span>mm&#44; and the percentage of patients referred from primary care providers was higher in 2021 &#40;89&#46;1&#37; vs 96&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46; The differences described here may have been due to at least two potential factors&#46; First&#44; the implementation of the US classification systems potentially allowed for extended surveillance periods&#44; leading to older patients and larger nodules&#46; This last observation is further corroborated by the results obtained by the comparison of group 1 with group 2 and with the 2015 cohort&#46; The nodules categorized with an US system &#40;group 1&#41; were significantly larger&#44; apparently at the cost of the nodules larger than one centimetre &#40;3<span class="elsevierStyleHsp" style=""></span>mm larger in diameter when compared to the nodules from group 2 and the 2015 cohort&#41;&#46; On the other hand&#44; it may also represent the impact of the COVID-19 pandemic&#46; It resulted in a delay in access to health care services and the emergence of financial-social difficulties&#44; leading to fewer patients resorting to private practice and a higher referral rate from primary care providers&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Comparing the nodule size per Bethesda category&#44; both Bethesda II and III category nodules were significantly larger in 2021 &#40;17<span class="elsevierStyleHsp" style=""></span>mm vs 19<span class="elsevierStyleHsp" style=""></span>mm&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;036&#59; 11<span class="elsevierStyleHsp" style=""></span>mm vs 23<span class="elsevierStyleHsp" style=""></span>mm&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;043&#44; respectively&#41;&#46; Bethesda V and VI nodules should not be compared regarding their dimensions due to the small sample size&#46; The size difference between the Bethesda III nodules &#40;12<span class="elsevierStyleHsp" style=""></span>mm&#41; is clinically relevant&#44; since the performing FNA in larger nodules is usually easier&#44; more successful&#44; and with a higher sensitivity&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">20&#44;21</span></a> However&#44; it is important to mention that the sample size of the Bethesda III nodules was small&#46; It seems that the US classification systems allow delaying FNA&#44; without aggravating the cytology results when FNA becomes indicated&#44; leading to larger nodules in 2021 undergoing FNA&#46; Even the detected size differences of 1 or 2<span class="elsevierStyleHsp" style=""></span>mm&#44; although not clinically relevant&#44; might be indicative of this positive trend&#46; As the Bethesda IV-VI categories have a small sample size not detecting differences regarding the nodules&#8217; dimensions and Bethesda category distribution&#44; it might be due to the low statistical power associated with small populations&#46; According to <a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3 and 4</a>&#44; we can perceive an apparent tendency towards bigger nodules in 2021 across the six Bethesda categories and a slight change in the distribution of the nodules throughout these categories from 2015 to 2021&#46; Regarding the Bethesda category distribution&#44; we could not make correlations with the US risk stratifying systems&#44; as an US classification system categorization was not applied in 41&#46;4&#37; of the 2021 nodules undergoing FNA&#46; However&#44; the most reported US category was EU-TIRADS 4&#46; We reported <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16 nodules EU-TIRADS 5 and <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5 nodules ACR-TIRADS 5&#44; however they did not correspond to the Bethesda V and VI nodules of the 2021 cohort&#46; As shown in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#44; none of these Bethesda V&#8211;VI nodules were classified as EU-TIRADS 5 or ACR-TIRADS 5&#46; The majority of the nodules EU-TIRADS 5 and ACR-TIRADS 5 undergoing FNA were Bethesda II&#46; Nonetheless&#44; in <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1 Bethesda V and <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1 Bethesda VI&#44; no US classification system was applied so we cannot exclude they would not be classified as EU-TIRADS 5 or ACR-TIRADS 5&#46; We acknowledge a very low percentage of Bethesda V and VI in our cohorts&#46; Possible explanations for the scarcity of higher risk Bethesda categories might be the high percentage of nodules referred for FNA that did not have criteria for it&#59; the fact that the US were performed by multiple radiologists with different degrees of experience in thyroid US &#40;being the majority non-exclusively dedicated to this type of US&#41;&#46; Another important factor to considered is that there is a potential referral bias associated with the IPATIMUP itself&#44; where the majority of the FNAs are requested by primary care providers&#44; as opposed to the hospital setting where they have a higher percentage of referrals from hospital specialties&#44; and nodules diagnosed in more complex contexts&#46; Additionally&#44; some more complicated situations are sent to IPATIMUP from private practice&#44; and occasionally from public hospitals&#44; namely&#44; consecutive Bethesda category I or III and&#47;or technically difficult to perform FNA biopsies&#46; These nodules might not have initially had an indication for FNA&#46; As the low rate of Bethesda V and VI was observed both in 2015 and 2021&#44; a potential referral bias and high percentage of referred nodules without an indication for FNA are the most plausible justifications&#46; A further topic of research in the IPATIMUP will be to assess in a larger population the potential variables responsible for this atypical low percentage of Bethesda V and VI categories in our sample and to have the statistical power to correlate the Bethesda categories with the US classification systems categories&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The most recent US-based classification systems<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#44;6&#44;8</span></a> &#40;and the ones included in this study&#41; are more conservative than the guidelines in force in 2015<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#44;12</span></a> regarding nodule size thresholds that indicate cytological assessment&#46; Nodules under one centimetre no longer indicate FNA&#44; even if high-risk factors are present&#44; as the course of papillary microcarcinoma is usually indolent&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> Consequently&#44; this leads to fewer FNA&#46; However&#44; in 2021&#44; nodules under 10<span class="elsevierStyleHsp" style=""></span>mm are still being referred to FNA&#46; At least 6&#46;6&#37; of nodules referred in 2021 were under 10<span class="elsevierStyleHsp" style=""></span>mm&#44; as opposed to 2015 &#40;at least 3&#46;2&#37;&#41;&#46; Nevertheless&#44; in 2015 we did not have access to the nodule size in 33&#46;5&#37; of the nodules&#44; and therefore a direct comparison between the two years should be interpreted with caution&#46; Even with several risk-stratification systems available in 2021&#44; nearly 40&#37; of the nodules are still not being stratified with an ultrasound classification system&#44; precluding the clinician to assess indication for FNA in virtually all of those nodules&#46; This goes along the same lines of a recent study reporting inconsistent and incomplete descriptions of thyroid nodules&#44; with some US features only being reported in as few as 9&#37; of the nodules&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> Consequently&#44; nearly all the 2021 nodules where we were able to assess the criteria for FNA were nodules classified with an US risk stratifying system &#40;98&#46;2&#37;&#41;&#44; and the <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3 nodules without this categorization that we were able to assess indication for FNA was due to the large dimensions of the nodules &#40;more than 20<span class="elsevierStyleHsp" style=""></span>mm in diameter&#41;&#46; Additionally&#44; at least 38&#37; of the nodules referred to FNA in 2021 did not have criteria to do it&#44; testifying that the clinicians do not always follow the recommendations associated with each risk category&#46; This might partly justify why the distribution of the Bethesda categories did not significantly change from 2015 to 2021&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The ongoing referral for biopsy of nodules under one centimetre in size and other nodules without indication for cytological assessment also shows us that other factors are accountable for this&#44; independently of these classification systems&#46; We could speculate some contributing factors are the patients&#8217; expectations&#44; as research shows office consults&#8217; satisfaction suffers and health-related anxiety increases when wanted diagnostic interventions are not obtained&#44;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">23&#44;24</span></a> and&#44; somewhat related&#44; the rise of defensive medicine in Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">25</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">It is pertinent to mention two important caveats concerning our data&#46; We had a significant percentage of missing data regarding nodule size in 2015 &#40;33&#46;5&#37; of the nodules&#41; and regarding information on US criteria to undergo FNA in both 2015 and 2021 &#40;65&#46;4&#37; vs 39&#46;2&#37;&#44; respectively&#41;&#46; To assess the indication for FNA of these nodules in 2015&#44; we had to use that limited data &#40;mainly&#44; the nodule size&#41;&#44; leading to a potential information bias without taking into consideration potential specific risk factors such as a history of thyroid cancer in first degree relatives&#44; history of external beam radiation as a child&#44; previous hemithyroidectomy with discovery of thyroid cancer&#44; and <span class="elsevierStyleSup">18</span>FDG avidity on PET scans&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> These factors are no longer considered in the updated systems&#44;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#44;6&#44;8</span></a> facilitating their application&#46; This study includes other limitations&#46; Thyroid US was performed by multiple radiologists introducing operator-driven variability that was not controllable&#46; However&#44; we can contemplate this as a strength of the study since the wide diversity of examiners with different levels of expertise performing the US led to a sample more representative of what is happening in daily clinical practice&#46; Another limitation was the retrospective design of this study&#44; leading to gaps in information&#46; The higher number of patients who underwent FNA in 2015 &#40;57&#37; more patients&#41; was due to institutional constraints associated with the availability of the pathologist performing this technique in the previous months&#44; leading to a bigger waitlist in October 2015&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusion</span><p id="par0190" class="elsevierStylePara elsevierViewall">This study is the first study to compare the reality in Portugal of thyroid FNA and cytology before and after the publication of the most commonly used US-based classification systems for thyroid nodules&#46; To the best of our knowledge&#44; it is also the first published study worldwide making this comparison and assessment&#46; This analysis draws attention to the importance of systematically applying US-based classification systems for thyroid nodules in our daily clinical practice&#46; It seems that these systems&#44; by not being focused mainly on size thresholds&#44; allow for extended surveillance periods&#44; without aggravating the cytology results when FNA becomes indicated&#46; FNA potentially become safer as the nodules are permitted to have larger dimensions&#46; Nevertheless&#44; bigger efforts are needed to ensure more standardized US reports by systematically using these risk-stratification systems and&#44; when applied&#44; to increase adherence to the resulting recommendations&#46; This will allow more consistent clinical decisions&#44; with a decrease in clinical uncertainty&#44; unnecessary FNA biopsies&#44; and potential overtreatment&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Ethical considerations</span><p id="par0195" class="elsevierStylePara elsevierViewall">All procedures were in accordance with the ethical standards of the institutional ethics committee and in line with the principles of the Declaration of Helsinki&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding sources</span><p id="par0200" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflict of interest</span><p id="par0205" class="elsevierStylePara elsevierViewall">No conflicts of interest in connection with this article&#46;</p></span></span>"
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              "titulo" => "Antecedentes"
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          "titulo" => "Introduction"
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          "titulo" => "Materials and methods"
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            0 => array:2 [
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              "titulo" => "Study design and patient selection"
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              "titulo" => "Data analysis and statistics"
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            0 => array:2 [
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              "titulo" => "Population characteristics"
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            1 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Characteristics of the thyroid nodules"
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            2 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "US classification systems"
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              "titulo" => "Cytology report"
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          "titulo" => "Acknowledgments"
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          "titulo" => "References"
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    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2022-04-12"
    "fechaAceptado" => "2022-06-30"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
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          "palabras" => array:4 [
            0 => "Thyroid nodule"
            1 => "Fine-needle"
            2 => "Biopsy"
            3 => "Ultrasonography"
          ]
        ]
      ]
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          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "N&#243;dulo tiroideo"
            1 => "Aguja fina"
            2 => "Biopsia"
            3 => "Ultrasonograf&#237;a"
          ]
        ]
      ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Several ultrasound-based systems for classification of thyroid nodules are available&#46; They allow for a better triage of the nodules that require cytological assessment&#44; and lead to standardized recommendations&#46; Our aim was to compare patients and nodules referred to fine-needle aspiration &#40;FNA&#41; before and after the introduction of these systems&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A retrospective study comparing two cohorts of patients referred for FNA was performed &#40;386 patients and 463 nodules in 2015&#59; 220 patients and 263 nodules in 2021&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The sex distribution &#40;89&#46;1&#37; vs 85&#46;9&#37; females&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;243&#41;&#44; number of nodules referred to FNA per patient &#40;median of 1&#41;&#44; and the distribution of the Bethesda categories &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;082&#41; was similar in both years&#46; In 2021&#44; patients were older &#40;53&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;5 years vs 57&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;2 years&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and nodules over one centimetre were larger &#40;median 17&#46;0<span class="elsevierStyleHsp" style=""></span>mm vs 19&#46;0<span class="elsevierStyleHsp" style=""></span>mm&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; especially the ones categorized as Bethesda III &#40;median size 11<span class="elsevierStyleHsp" style=""></span>mm vs 23<span class="elsevierStyleHsp" style=""></span>mm&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;043&#41;&#46; In 2021&#44; at least 23&#46;1&#37; of the nodules referred to FNA did not have any criteria&#44; and 38&#46;8&#37; of the nodules were not categorized by any system&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This analysis draws attention to the importance of systematically applying ultrasound-based classification systems&#46; It seems that&#44; by not being focused mainly on size thresholds&#44; they allow for longer surveillance periods&#44; without aggravating the cytology results when FNA becomes indicated&#46; Nevertheless&#44; greater efforts are needed to ensure more standardized reports&#44; and to increase adherence to the resulting recommendations to reduce clinical uncertainty&#44; unnecessary FNA&#44; and overtreatment&#46;</p></span>"
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            "titulo" => "Background"
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            "titulo" => "Methods"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Existen varios sistemas basados en la ecograf&#237;a para la clasificaci&#243;n de los n&#243;dulos tiroideos&#46; Permiten un mejor triaje de los n&#243;dulos que requieren una evaluaci&#243;n citol&#243;gica y conducen a recomendaciones estandarizadas&#46; Nuestro objetivo fue comparar los pacientes y los n&#243;dulos remitidos para punci&#243;n aspiraci&#243;n con aguja fina &#40;PAAF&#41; antes y despu&#233;s de la introducci&#243;n de estos sistemas&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio retrospectivo comparando 2 cohortes de pacientes remitidos para PAAF &#40;386 pacientes y 463 n&#243;dulos en 2015&#59; 220 pacientes y 263 n&#243;dulos en 2021&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La distribuci&#243;n por g&#233;nero &#40;89&#44;1&#37; vs&#46; 85&#44;9&#37; mujeres&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;243&#41;&#44; el n&#250;mero de n&#243;dulos remitidos para PAAF por paciente &#40;mediana&#58; 1&#41; y la distribuci&#243;n de las categor&#237;as Bethesda &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;082&#41; fue similar en ambos a&#241;os&#46; En 2021 los pacientes eran de mayor edad &#40;53&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;5<span class="elsevierStyleHsp" style=""></span>a&#241;os vs&#46; 57&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#44;2<span class="elsevierStyleHsp" style=""></span>a&#241;os&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y los n&#243;dulos supracentim&#233;tricos eran mayores &#40;mediana 17&#44;0<span class="elsevierStyleHsp" style=""></span>mm vs&#46; 19&#44;0<span class="elsevierStyleHsp" style=""></span>mm&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#44; especialmente los Bethesda III &#40;mediana 11<span class="elsevierStyleHsp" style=""></span>mm vs&#46; 23<span class="elsevierStyleHsp" style=""></span>mm&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;043&#41;&#46; En 2021 al menos el 23&#44;1&#37; de los n&#243;dulos remitidos a PAAF no ten&#237;an criterios&#44; y el 38&#44;8&#37; de los n&#243;dulos no fueron categorizados por ning&#250;n sistema&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este an&#225;lisis llama la atenci&#243;n sobre la importancia de aplicar este sistemas de clasificaci&#243;n&#46; Parece que&#44; al no estar centrados principalmente en el tama&#241;o&#44; permiten per&#237;odos de vigilancia m&#225;s prolongados&#44; sin agravar la citolog&#237;a cuando se indica la PAAF&#46; No obstante&#44; es necesario realizar mayores esfuerzos para garantizar informes m&#225;s estandarizados y aumentar la adherencia a las recomendaciones resultantes&#44; con el fin de reducir la incertidumbre cl&#237;nica y las PAAF innecesarias&#46;</p></span>"
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            "identificador" => "abst0025"
            "titulo" => "Antecedentes"
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            "titulo" => "M&#233;todos"
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          2 => array:2 [
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">FNA&#44; fine needle aspiration&#59; SD&#44; standard deviation&#46;</p>"
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                  \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>386 patients&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>220 patients&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Gender&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">31 &#40;14&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">189 &#40;85&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">344 &#40;89&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">42 &#40;10&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Patients submitted to FNA&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 nodule&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">316 &#40;81&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">180 &#40;81&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;993&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 nodules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63 &#40;16&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;16&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3 nodules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">General characteristics of the patients from 2015 and from 2021&#46;</p>"
        ]
      ]
      1 => array:8 [
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
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            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ACR&#44; American College of Radiology&#59; ATA&#44; American Thyroid Association&#59; EU&#44; European&#59; NA&#44; not applicable&#59; TIRADS&#44; Thyroid Imaging Reporting and Data System&#59; US&#44; ultrasound&#46;</p>"
          "tablatextoimagen" => array:2 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">US classification system used <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">EU-TIRADS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ACR-TIRADS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ATA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Not referred&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">107 &#40;39&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 &#40;21&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;0&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106 &#40;38&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
            1 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">US classification system category&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">EU-TIRADS &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>107&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ACR-TIRADS &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ATA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Not known &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>106&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Class 1&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Class 2&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Class 3&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;27&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;46&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Class 4&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52 &#40;48&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;37&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Class 5&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;15&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;8&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Not referred&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;6&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Distribution of the 273 nodules from 2021 as per the US classification system used and corresponding category&#46;</p>"
        ]
      ]
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          0 => array:3 [
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          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">AUS&#47;FLUS&#58; Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Bethesda classification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">2015 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>463&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2021 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>263&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group 1 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>102&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group 2 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>161&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I &#8211; Non diagnostic&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 &#40;12&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;9&#46;1&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;29&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;70&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II &#8211; Benign&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">366 &#40;79&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">215 &#40;81&#46;7&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87 &#40;40&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">128 &#40;59&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III &#8211; AUS&#47;FLUS&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;3&#46;8&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV &#8211; Follicular tumour&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;3&#46;8&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">V &#8211; Suspicious for malignancy&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;1&#46;1&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VI &#8211; Malignant&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#46;4&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          ]
        ]
        "descripcion" => array:1 [
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      ]
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">AUS&#47;FLUS&#58; Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bethesda classification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2015 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>463&#41; median size&#44; mm&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2021 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>263&#41; median size&#44; mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I &#8211; Non diagnostic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;642&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II &#8211; Benign&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">IV &#8211; Follicular tumour&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">ACR&#44; American College of Radiology&#59; ATA&#44; American Thyroid Association&#59; EU&#44; European&#59; NA&#44; Not applicable&#59; TIRADS&#44; Thyroid Imaging Reporting and Data System&#59; US&#44; Ultrasound&#46;</p>"
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Article information

ISSN: 25300164
Original language: English

DOI:10.1016/j.endinu.2022.06.008

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Year/Month	Html	Pdf	Total

2024 November	5	3	8
2024 October	27	17	44
2024 September	37	40	77
2024 August	37	18	55
2024 July	34	14	48
2024 June	34	17	51
2024 May	38	12	50
2024 April	31	6	37
2024 March	22	17	39
2024 February	20	5	25
2024 January	17	5	22
2023 December	24	3	27
2023 November	22	5	27
2023 October	36	3	39
2023 September	19	3	22
2023 August	23	1	24
2023 July	34	4	38
2023 June	12	0	12
2023 May	8	2	10
2023 April	8	1	9
2023 March	6	7	13
2023 February	5	4	9
2023 January	10	7	17
2022 December	5	14	19
2022 November	0	12	12
2022 October	0	3	3

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