Original article
Thyroid carcinoma in children and adolescents: A retrospective review
Carcinoma tiroideo en niños y adolescentes: estudio retrospectivo
Filipa Neiva
, Joana Mesquita, Susana Paco Lima, Maria João Matos, Carla Costa, Cintia Castro-Correia, Manuel Fontoura, Sofia Martins
Corresponding author
Unidade de Endocrinologia Pediátrica, Serviço Pediatria, Hospital São João, Porto, Portugal
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There is a female predominance, with a female–male ratio 2.5–6:1.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Patients typically present with a cervical mass but may also present with cervical lymphadenopathy, voice changes, or hyperthyroidism.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">When compared to adults, palpable thyroid nodules are less common in children and adolescents, with an incidence of 1.5%.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> However, the rate of malignancy among pediatric thyroid nodules is approximately 16%, about three times that of adults. In pediatric population there is also a much greater incidence of lymph node metastasis (40–80%) and distant metastasis (25%),<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> but without an overall increase in mortality.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">High risk factors for thyroid carcinoma are younger age, male sex, large primary tumor size, extrathyroidal tumor extension, palpable lymph nodes, distant metastases at diagnosis, residual cervical disease after thyroidectomy, inadequate thyroid hormone suppression, diffuse sclerosing, or follicular thyroid histology.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The authors present a retrospective review of all cases of thyroid carcinomas followed by pediatric endocrinology in S. João Hospital during the time period of the study.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">Cases were identified by searching the Department of Pathology database, for confirmed histologic diagnosis of thyroid carcinoma (TC) in patients less than 18 years at presentation. All tissues were obtained after surgical intervention (hemithyroidectomy, completion thyroidectomy [CT] or total thyroidectomy [TT]) at Hospital S. João, Porto, from January 1, 2000 to March 31, 2010.</p><p id="par0035" class="elsevierStylePara elsevierViewall">A retrospective study was undertaken. A review of health records was conducted to determine patient demographics, risk factors, family history of thyroid disorders or malignancies, preoperative thyroid function, interventions (surgery and radioactive iodine [RAI]), and follow-up data. Data collection ended in May 30, 2011.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Tumor staging was performed based on the TNM (tumor-node-metastases) tumor classification system.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> All patients aged less than 45 years (all in this study) were classified as stage 1 (any T, any N, M0) or stage 2 (any T, any N, M1). Staging was assessed using data collected after thyroidectomy.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using SPSS 17.0; analysis of variance was used as appropriate depending on the continuous or discrete nature of the data. Multiple regression analysis was performed on selected clinically important variables. Significance was set at <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The study was approved by the Hospital S. João pediatric endocrinology coordinator and an informed consent was signed by parents or children legal guardian.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">Twenty-three eligible cases were identified, including 19 girls and four boys; median age at presentation was 17.0 years (range 10–18 years). Annual incidence was 2.3<span class="elsevierStyleHsp" style=""></span>cases/year. The distribution of newly diagnosed patients was maximal in 2003 (6 cases), followed by the years 2000 and 2005 (4 cases each), no new case in 2007.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The main presenting motive was a solitary thyroid nodule with (7–30.4%) or without (7– 30.4%) associated systemic symptoms (namely anorexia, asthenia, dysphagia, cough, dyspnea, weight loss, polydipsia, and hyperthyroidism symptoms), followed by a palpable lateral cervical mass (3 – 13%) and accidentally detected mass in routine medical exam (3–13%); in one patient asthenia was the sole complaint. No data available about the clinical presentation in two of the patients. The symptoms started 10.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.2 (range 1–48) months before seeking medical attention (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17). Three (13%) patients had risk factors for TC: 2 (8.7%) had received external therapeutic radiation for treatment of previous malignancies (Hodgkin lymphoma – last treatment 10.3 and 2.9 years before) and 1 was a smoker. One patient had preexisting thyroid disease (Grave's disease) and 2 were under prescription of thyroid medication: 1 L-thyroxin and 1 propylthiouracil. Six patients had family history of thyroid disease, although there is no family record of TC.</p><p id="par0065" class="elsevierStylePara elsevierViewall">On the initial endocrine evaluation (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21), 15 had normal thyroid function, 3 had thyrotoxicosis (raised thyroxin [T4] and decreased thyroxin stimulating hormone [TSH]) and 3 had hypothyroidism (decreased T4 and elevated TSH). Four (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9) had positive antithyroid antibodies (antithyroglobulin and antiperoxidase antibodies) and 18 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>23) had abnormal thyroid description in neck ultrasound. Hypoechogenic thyroid nodules described in 8 patients, nodules associated with cervical lymph node enlargement in five, calcificated nodules in two, and goiter in two. On physical exam 19 patients had abnormal thyroid palpation. Pubertal data were incomplete in medical records, and hence could not be evaluated.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Fine needle aspiration biopsy (FNAB) was performed in 17 patients and led to diagnosis of TC. In the reminder the diagnosis was established by histology after thyroidectomy.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Total thyroidectomy (TT) was performed in 16 (69.6%), with radical unilateral cervical lymph node dissection in 4 patients. Seven were treated with initial hemithyroidectomy. Ten patients underwent a second surgical procedure after review of the final pathology result of initial procedure or in the follow-up. The re-operated patients can be separated in two groups: group 1 – those who were submitted to TT after initial hemithyroidectomy or incomplete TT (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7, mean 3.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.9 months after first procedure); group 2 – patients that were submitted to cervical node dissection (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3, mean 96.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>55.7, range 3–108 months).</p><p id="par0080" class="elsevierStylePara elsevierViewall">Four (17.4%) patients had postoperative complications, 2 persistent hypocalcemia and 2 transient hoarseness (one with associated transient hypocalcemia), which recovered spontaneously.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Histology revealed papillary thyroid carcinoma (PTC) in 20/23 patients (86.9%), 2 (8.7%) had diffuse sclerosing-PTC, and papillary TC-follicular variant in 7 (30.4%). In the remaining 3 patients follicular carcinoma was detected. Multiple tumor foci of papillary type were detected in 5 patients. Tumor size (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>18) ranged from 0.2 to 4.5<span class="elsevierStyleHsp" style=""></span>cm (maximum diameter); 2 children had tumors measuring <1.0. Eighteen (78.3%) had stage 1 disease and 5 (21.7%) had stage 2 (4 patients had lung metastasis and 1 had thymic metastases). Four of the patients with stage 2 disease were males. TNM staging details of all patients are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Twenty (87.0%) patients underwent therapeutic radioactive iodine (RAI), with a range of 1–6 doses. The first RAI treatment was done 5.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.1 months postoperative, 11 received first treatment within 3 months after surgery. Thyroid hormone therapy was applied in all patients.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The mean duration of follow-up was 84.9 months (range: 12–134 months). Seven patients presented new metastases in the cervical, mediastinal lymph nodes, lungs, and bones and need treatment during follow-up, 2 were re-operated and the others received additional RAI treatment. When patients completed 19 years they began to be followed by an adult endocrinologist. The patients were followed by clinical examination, thyroid and neck ultrasound, TSH, T4, and serum Tg levels every 6 months in order to detect recurrence or progression of the disease. Other exams (e.g. body cintigraphy) were performed when necessary.</p><p id="par0100" class="elsevierStylePara elsevierViewall">All patients are alive and currently asymptomatic, but one patient had residual disease detected in FNAB in last follow-up (March 2011) and was referred to surgery.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Patients found to have TC in stage 2 was correlated with male sex (<span class="elsevierStyleItalic">X</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17.4; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001), and older age (<span class="elsevierStyleItalic">X</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>28.3; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01). However, not related with histology, tumor size or need to re-intervention. Tumor diameter was not correlated with histology. Neither positive titer of thyroid peroxidase antibodies, nor TSH abnormal levels were associated with advanced disease (TNM classification).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">Although TC is known as an adult disease it is a reality in pediatric population. It is of the general knowledge that its occurrence and clinical course are different from those of the adult.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Because most (up to 93%) of the thyroid malignancies in this age group tend to be well differentiated, and despite a tendency for children to present with advanced disease (including pulmonary metastases), survival outcomes are favorable (80–100% at age of 30 years).<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The annual number of children found to have TC at our institution did not increase during the time period of the study and the annual variation is not significant. Unfortunately, in our country there is no oncologic database in order to know the true incidence of TC in this age group, as well as its evolution over time. Other recognized study handicap is that our hospital is not the single hospital that attends and follows TC in our region, and so the true incidence of this disease remains unknown. Nevertheless, the current study is one of the first Portuguese studies addressing clinical data in the field of TC in children and adolescents. It is limited by the inherent bias of a retrospective review, and lacks some details, particularly in the oldest cases (without computerized clinical data).</p><p id="par0120" class="elsevierStylePara elsevierViewall">The major conclusions are discussed below. The female to male ratio in our patients was 4.75–1, which is consistent with published data.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,8</span></a> Male were more likely to have disseminated disease at presentation (stage 2 in 100%), this is in keeping with previous studies that report that boys are more prone to develop subsequent metastases as well as have decreased disease-free survival.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The initial clinical complaint was a thyroid nodule or cervical mass in the majority (73.9%) of our patients, and this is the most common presentation form of TC described (60–80%).<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> There was a background of clinical thyroid disease in 1 patients and other 2 (8.7%) had developed TC has a secondary malignancy after treatment of a primary disease with cervical radiation. In fact, TC accounts for about 10% of second malignancies among cancer survivors, especially Hodgkin lymphoma, due to treatment not only with radiation but also with alkylating agents.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> So, this study supports the importance to render special attention in patients with known risk factors for TC. Some clinicians advocate that regular ultrasonography to screen for thyroid nodules, with precocious biopsies in suspicious nodules should take part of a regular follow up in cancer survivors.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Cervical exam on first evaluation was abnormal in 82.6% of the cases, what reinforces the importance of thyroid palpation as part of physical exam in children and adolescents. There are a number of well-established predictors of malignancy in thyroid nodules that include hard and fixed lesions, rapid growth of nodules, large size, associated hoarseness, dysphagia, or lymphadenopathy.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> There are also suspicious ultrasonographic characteristics of thyroid nodules associated with higher risk: hypoechoic and solid, and in addition have microcalcifications, irregular borders, central blood flow on Doppler imaging, and a high anteroposterior to transverse ratio.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Ten (43.5%) of our patients had high risk nodules description in the initial study. We only have information about the nodule diameter and no data about anteroposterior to transverse ratio.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Thyroid function was normal in 71.4% of the cases which is consistent with published data.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> We found no relation between abnormal TSH level or positive titer of thyroid antibodies with disease stage, but that could be due to the small number of patients of our series.</p><p id="par0130" class="elsevierStylePara elsevierViewall">FNAB proved its diagnostic value, in all cases (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17) with prior FNAB the diagnostic was established with this technique. All TCs were well differentiated and 86.9% of our patients had papillary carcinoma, similar distribution has been reported by other authors.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2,6</span></a> Complications rate after surgery was low in the current study and must be so in general if patients are referred to specialized surgeons.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,6</span></a> The majority of authors recommend total or near-total thyroidectomy as the initial approach of TC<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>; in our series only one patient treated with initial hemithyroidectomy did not require re-intervention. Twenty of our 23 patients (87.0%) had received additional therapy with radioactive <span class="elsevierStyleSup">131</span>I; however, there were no complete data regarding the doses and so no conclusions can be determined with this information. No patient had radioiodine-related secondary malignancies over the follow-up period, which is short. The risk is small but does exist.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> All patients received suppressive doses of L-thyroxine and were closely monitored as defined by current guidelines.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Our survival rate was 100%, but at last follow-up one patient had residual disease. Considering the slow course of TC, this is a relatively short time of median follow-up (7.1 years). Continued monitoring is needed and the close contact between pediatric and adult a life-long period in order to recognize and treated promptly any local or distant metastasis. A temporal extension of the study will allow more reliable conclusions.</p><p id="par0140" class="elsevierStylePara elsevierViewall">In summary, even those children and adolescents with advanced TC have an overall good prognosis. A national oncologic database is needed with the intention of improving our understanding of this pathology, prompt diagnosis and optimizing treatment of pediatric TC.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres148708" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objective" 2 => "Material and methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec136608" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres148709" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivo" 2 => "Material y métodos" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec136607" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-08-10" "fechaAceptado" => "2011-11-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec136608" "palabras" => array:2 [ 0 => "Retrospective study" 1 => "Thyroid carcinoma" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec136607" "palabras" => array:2 [ 0 => "Estudio retrospectivo" 1 => "Cáncer de tiroides" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To describe clinical presentation, preoperative study, intervention, histology, surgical complications and follow-up characteristics, and survival in patients with thyroid carcinoma (TC) with less than 18 years at presentation.</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">retrospective analysis of clinical data of all children and adolescents followed in S. João Hospital from January 1, 2000 to March 31, 2010 with histologic diagnosis of TC.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Twenty-three patients were identified, 19 girls, and 4 boys. Median age at presentation was 17.0 years. Annual incidence was 2.3 cases/year. The main presenting symptom was a solitary thyroid nodule (60.8%). Three (13%) patients had risk factors for TC, 2 of the 3 had previous cervical irradiation. The other was a smoker. Total thyroidectomy was performed in 16 (69.6%), and 10 patients underwent a second surgical procedure. Four (17.4%) patients had postoperative complications. Histologic examination revealed differentiated TC in all, papillary thyroid carcinoma (PTC) in 86.9%, follicular carcinoma in the remaining. All patients received thyroxine suppressive therapy and 20 underwent therapeutic radioactive iodine (<span class="elsevierStyleSup">131</span>I). During follow-up (7.1 years), 7 out of the 23 patients presented new metastases and needed new treatment. All patients are currently alive.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">TC is a reality in pediatric population, thyroid routine examination should take part in all clinical examination in children and adolescents.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Describir la presentación clínica, el estudio preoperatorio, la intervención quirúrgica y complicaciones, así como la histología, el seguimiento y la supervivencia de pacientes con carcinoma tiroideo (CT) cuya edad es inferior a los 18 años en el momento de la presentación.</p> <span class="elsevierStyleSectionTitle">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">análisis retrospectivo de los datos clínicos de todos los niños y adolescentes con diagnóstico histológico de CT seguidos en el Hospital São João, Oporto, desde el 1 de enero de 2000 hasta el 31 de marzo de 2010.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">se identificaron veintitrés pacientes, 19 niñas y 4 niños. La mediana de la edad de presentación fue de 17,0 años con una incidencia anual de 2,3 casos/año. El síntoma principal de presentación (60,8%) fue nódulo tiroideo solitario. Tres (13%) de los pacientes presentaban factores de riesgo para CT, 2 de los 3 habían recibido irradiación cervical. El otro era un fumador. Se realizó una tiroidectomía total en 16 pacientes (69,6%), 10 pacientes necesitaron una segunda intervención quirúrgica. Cuatro (17,4%) presentaron complicaciones postoperatorias. El examen histológico reveló CT diferenciado en todos los casos, con carcinoma papilar tiroideo en el 86,9% y carcinoma folicular en los restantes. Todos los pacientes recibieron tratamiento supresor con tiroxina y 20 recibieron tratamiento con yodo radiactivo terapéutico. Durante el seguimiento (7,1 años), 7 de los 23 pacientes presentaron nuevas metástasis y necesitaron un nuevo tratamiento. Todos los pacientes están vivos en la actualidad.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El CT es una realidad entre la población pediátrica y los exámenes clínicos de niños y adolescentes debería incluir siempre una examen rutinario del tiroides.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">TNM staging</td></tr><tr title="table-row"><td 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" style="border-bottom: 2px solid black">T \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">N \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">M \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">No. of patients (%) \t\t\t\t\t\t\n \t\t\t\t</td></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 " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T1</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">N0 \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">M0 \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 (26.1) \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N1 \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">M0 \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 (13.0) \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 " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T2</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">N1 \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">M0 \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 (8.6) \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N1 \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">M1 \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 (4.3) \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 " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T3</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">N0 \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">M0 \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 (4.3) \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N1 \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">M0 \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 (13.0) \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 " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T4</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">N1 \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">M0 \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 (8.6) \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N1 \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">M1 \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">4 (17.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab242746.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">TNM staging details of patients (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>22).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thyroid carcinoma in children and adolescents, Presentation, clinical course, and outcome of theraphy in 23 children and adolescents in Northern Greece" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Pazaitou-Panayiotou" 1 => "A. Kaprara" 2 => "M. Boudina" 3 => "E. Georgiou" 4 => "A. Drimonitis" 5 => "E. Raptou" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hormones" "fecha" => "2005" "volumen" => "4" "paginaInicial" => "213" "paginaFinal" => "220" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16613819" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Câncer de Tireóide na Infância e Adolescência – Relato de 15 Casos" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Cardoso" 1 => "M. Pianovsky" 2 => "S. França" 3 => "R. Pereira" 4 => "M. Boguzewski" 5 => "R. Sandrini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Arq Bras Endocrinol Metab" "fecha" => "2004" "volumen" => "48" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and management of pediatric endocrine neoplasms" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Iqbala" 1 => "D. Wahoff" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MOP.0b013e32832b335e" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Pediatr" "fecha" => "2009" "volumen" => "21" "paginaInicial" => "379" "paginaFinal" => "385" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19421059" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The thyroid nodule" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "L. Wartofsky" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:4 [ "titulo" => "Thyroid cancer: a comprehensive guide to clinical management" "paginaInicial" => "3" "paginaFinal" => "7" "serieFecha" => "2000" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic utility of fine-needle aspiration cytology in pediatric differentiated thyroid cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Bargren" 1 => "G. Meyer-Rochow" 2 => "M. Sywak" 3 => "L. Delbridge" 4 => "H. Chen" 5 => "S. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 7 | 5 | 12 |
| 2024 September | 12 | 13 | 25 |
| 2024 August | 21 | 6 | 27 |
| 2024 July | 14 | 4 | 18 |
| 2024 June | 13 | 5 | 18 |
| 2024 May | 12 | 3 | 15 |
| 2024 April | 14 | 6 | 20 |
| 2024 March | 10 | 3 | 13 |
| 2024 February | 13 | 9 | 22 |
| 2024 January | 7 | 1 | 8 |
| 2023 December | 19 | 5 | 24 |
| 2023 November | 17 | 8 | 25 |
| 2023 October | 15 | 6 | 21 |
| 2023 September | 7 | 4 | 11 |
| 2023 August | 4 | 4 | 8 |
| 2023 July | 5 | 9 | 14 |
| 2023 June | 4 | 1 | 5 |
| 2023 May | 10 | 9 | 19 |
| 2023 April | 7 | 2 | 9 |
| 2023 March | 7 | 2 | 9 |
| 2023 February | 4 | 9 | 13 |
| 2023 January | 6 | 7 | 13 |
| 2022 December | 10 | 5 | 15 |
| 2022 November | 16 | 9 | 25 |
| 2022 October | 15 | 8 | 23 |
| 2022 September | 7 | 8 | 15 |
| 2022 August | 11 | 12 | 23 |
| 2022 July | 11 | 7 | 18 |
| 2022 June | 8 | 8 | 16 |
| 2022 May | 30 | 7 | 37 |
| 2022 April | 23 | 10 | 33 |
| 2022 March | 11 | 9 | 20 |
| 2022 February | 4 | 4 | 8 |
| 2022 January | 11 | 5 | 16 |
| 2021 December | 11 | 12 | 23 |
| 2021 November | 6 | 8 | 14 |
| 2021 October | 11 | 9 | 20 |
| 2021 September | 6 | 12 | 18 |
| 2021 August | 6 | 3 | 9 |
| 2021 July | 7 | 9 | 16 |
| 2021 June | 12 | 9 | 21 |
| 2021 May | 12 | 14 | 26 |
| 2021 April | 17 | 22 | 39 |
| 2021 March | 12 | 9 | 21 |
| 2021 February | 8 | 6 | 14 |
| 2021 January | 10 | 17 | 27 |
| 2020 December | 7 | 10 | 17 |
| 2020 November | 6 | 9 | 15 |
| 2020 October | 7 | 9 | 16 |
| 2020 September | 9 | 39 | 48 |
| 2020 August | 9 | 35 | 44 |
| 2020 July | 11 | 10 | 21 |
| 2020 June | 5 | 8 | 13 |
| 2020 May | 7 | 8 | 15 |
| 2020 April | 10 | 6 | 16 |
| 2020 March | 5 | 6 | 11 |
| 2020 February | 4 | 4 | 8 |
| 2020 January | 7 | 11 | 18 |
| 2019 December | 14 | 6 | 20 |
| 2019 November | 11 | 10 | 21 |
| 2019 October | 5 | 1 | 6 |
| 2019 September | 12 | 8 | 20 |
| 2019 August | 7 | 2 | 9 |
| 2019 July | 8 | 8 | 16 |
| 2019 June | 6 | 17 | 23 |
| 2019 May | 45 | 36 | 81 |
| 2019 April | 14 | 2 | 16 |
| 2019 March | 8 | 5 | 13 |
| 2019 February | 3 | 4 | 7 |
| 2019 January | 11 | 0 | 11 |
| 2018 December | 10 | 5 | 15 |
| 2018 November | 17 | 3 | 20 |
| 2018 October | 8 | 2 | 10 |
| 2018 September | 4 | 0 | 4 |
| 2018 August | 4 | 4 | 8 |
| 2018 July | 6 | 7 | 13 |
| 2018 June | 7 | 1 | 8 |
| 2018 May | 4 | 5 | 9 |
| 2018 April | 3 | 5 | 8 |
| 2018 March | 6 | 1 | 7 |
| 2018 February | 2 | 2 | 4 |
| 2018 January | 10 | 0 | 10 |
| 2017 December | 6 | 2 | 8 |
| 2017 November | 8 | 1 | 9 |
| 2017 October | 11 | 4 | 15 |
| 2017 September | 21 | 2 | 23 |
| 2017 August | 10 | 2 | 12 |
| 2017 July | 18 | 2 | 20 |
| 2017 June | 18 | 7 | 25 |
| 2017 May | 13 | 4 | 17 |
| 2017 April | 17 | 6 | 23 |
| 2017 March | 23 | 3 | 26 |
| 2017 February | 29 | 1 | 30 |
| 2017 January | 5 | 0 | 5 |
| 2016 December | 13 | 4 | 17 |
| 2016 November | 15 | 3 | 18 |
| 2016 October | 34 | 1 | 35 |
| 2016 September | 12 | 2 | 14 |
| 2016 August | 5 | 2 | 7 |
| 2016 July | 13 | 1 | 14 |
| 2016 June | 10 | 11 | 21 |
| 2016 May | 7 | 0 | 7 |
| 2016 April | 9 | 1 | 10 |
| 2016 March | 11 | 5 | 16 |
| 2016 February | 7 | 5 | 12 |
| 2016 January | 6 | 4 | 10 |
| 2015 December | 7 | 4 | 11 |
| 2015 November | 8 | 3 | 11 |
| 2015 October | 15 | 5 | 20 |
| 2015 September | 10 | 3 | 13 |
| 2015 August | 12 | 4 | 16 |
| 2015 July | 6 | 3 | 9 |
| 2015 June | 6 | 0 | 6 |
| 2015 May | 14 | 2 | 16 |
| 2015 April | 11 | 5 | 16 |
| 2015 March | 8 | 3 | 11 |
| 2015 February | 8 | 0 | 8 |
| 2015 January | 31 | 6 | 37 |
| 2014 December | 26 | 6 | 32 |
| 2014 November | 9 | 1 | 10 |
| 2014 October | 24 | 5 | 29 |
| 2014 September | 19 | 2 | 21 |
| 2014 August | 21 | 1 | 22 |
| 2014 July | 15 | 3 | 18 |
| 2014 June | 20 | 2 | 22 |
| 2014 May | 22 | 3 | 25 |
| 2014 April | 14 | 1 | 15 |
| 2014 March | 7 | 2 | 9 |
| 2014 February | 18 | 2 | 20 |
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