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"nombre" => "Antoni" "apellidos" => "Rigó" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Alberto" "apellidos" => "Codina" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Julia" "apellidos" => "de Juan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Miquel" "apellidos" => "Quer" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "Xavier" "apellidos" => "León" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Otorrinolaringología, Hospital Josep Trueta, Girona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Otorrinolaringología, Hospital de Sant Pau, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Significado pronóstico de la extensión extranodal en pacientes con carcinomas escamosos de cabeza y cuello cN0 con metástasis ganglionares ocultas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2185 "Ancho" => 1527 "Tamanyo" => 147528 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Disease-specific survival according to the seventh and eighth editions of TNM classification of malignant tumours.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Capsular rupture, or extranodal extension (ENE) according to the terminology of the Union for International Cancer Control, was first described by Willis<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">1</span></a> en 1930 when he noted that some squamous cell carcinomas are able to break the lymph node capsule and infiltrate surrounding tissues. The clinical importance of the presence of metastatic lymph nodes with ENE has been known since the nineteen seventies, when Bennett et al.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">2</span></a> established that it was an independent factor of poor prognosis for carcinomas of the larynx and hypopharynx. In the nineteen eighties, several studies concluded that the presence of ENE was one of the most significant prognostic factors in patients with head and neck squamous cell carcinomas (HNSCC).<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">3,4</span></a> Various multivariate studies on prognostic factors in patients with HNSCC draw the same conclusions.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">4–9</span></a> Chiesa et al.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">10</span></a> published a review of the prognostic factors for HNSCC, including ENE in the category of prognostic factors for which significance is still controversial, together with other biological factors of the tumour itself.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In 2013<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">11</span></a> we undertook a study on the prognostic influence of ENE in patients with HNSCC, and were able to establish that the inclusion of ENE in the pathological lymph node staging (pN) of patients treated with neck surgery improved prognostic capacity with respect to the seventh edition of the TNM.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Depending on the location and extension of the primary tumour, a variable percentage of clinically and radiologically cN0 patients had occult lymph node metastases (cN0/pN+) in neck dissections. This justifies performing elective neck surgery on these types of patients. A proportion of cN0/pN+ patients have lymph nodes with ENE. According to the eighth edition of the TNM,<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">13</span></a> the pN category that would correspond to these patients with ENE would be higher than that of the seventh edition.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the new edition of the TNM, ENE is included as a criterion for clinical (cN) and pathological (pN) classification. In terms of pathologic classification, patients with a single ipsilateral lymph node metastasis, less than 3<span class="elsevierStyleHsp" style=""></span>cm and without ENE would be categorised as pN1. In the case of ENE, a patient with a tumour of these characteristics would be classified as pN2a. The patients classified as pN2 according to the seventh edition of the TNM classification, would only remain in this category in the absence of ENE. If at least one ruptured lymph node appears, the patients would then be classified as pN3b. Finally, patients with metastases larger than 6<span class="elsevierStyleHsp" style=""></span>cm would be classified as pN3a or pN3b, according to the absence or presence of ENE, respectively (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The objective of this study was to assess the influence of the appearance of occult lymph node metastases with ENE in patients with no clinical or radiological evidence of lymph node involvement (cN0) treated with neck dissection, and to evaluate the changes in the prognostic capacity of including ENE as a histopathological classification criterion in the eight edition of the TNM for these types of patients.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">This study was performed retrospectively from data gathered prospectively and included in a database with information from patients with malignant head and neck tumours diagnosed and treated in our hospital since 1985.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The inclusion criteria for the patients analysed in this study were: (1) no history of a previous head and neck tumour; (2) a histologically confirmed infiltrating squamous cell carcinoma in the oral cavity, oropharynx, hypopharynx or larynx, with no metastatic lymph nodes on initial clinical or radiological examination (cN0), diagnosed and treated from 1992 to 2014; (3) not having had previous treatment to the lymph node area; (4) having undergone elective neck dissection, and (5) a minimum 2-year follow up.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We did not include patients treated before 1992 in this study due to the lack of certainty that the initial extension study would have included an imaging study in addition to neck palpation. From that date, all of the HNSCC patients who were candidates for neck surgery were assessed by radiological examination (CT and/or MRI and/or PET-CT) which revealed no suspicious lesions in the area of the neck. All of the patients were evaluated by our hospital's oncological committee, who determined whether a neck dissection was appropriate.</p><p id="par0045" class="elsevierStylePara elsevierViewall">During the period from 1992 to 2014, a total of 354 cN0 patients were treated by elective neck dissection. A total of 4 patients who did not complete the 3-year follow-up period, and 2 with HPV-positive oropharyngeal tumours, with a specific classification in the eighth edition of the TNM were excluded. This study was performed on a cohort of 348 HNSCC CN0 patients who underwent elective neck surgery with a minimum follow-up of 2 years. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the features of the patients included in this study.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Information was obtained on the type of dissection performed, the number of lymph nodes dissected, the number of positive lymph nodes, and the presence of lymph nodes with ENE. ENE was defined as infiltration by the tumour cells through the lymph node capsule. Our hospital's pathological report does not include information on the microscopic or macroscopic characteristics of ENE. The patients were classified according to the absence of metastatic lymph nodes in the dissections (cN0/pN0), to the presence of lymph node metastasis with no ENE (pN+/ENE−), or the presence of lymph node metastasis with ENE (pN+/ENE+).</p><p id="par0055" class="elsevierStylePara elsevierViewall">A total of 95 patients were treated with unilateral dissections and 253 with bilateral dissections. Functional or selective dissections were performed in the majority, depending on the location and the characteristics of the primary tumour. An average of 34.7 (standard deviation 16.7<span class="elsevierStyleHsp" style=""></span>m, range 9–101) lymph nodes was resected per patient. Treatment of the primary tumour comprised surgical removal in all the cases studied, with the exception of 4 patients who underwent local treatment with brachytherapy.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Fifty-one point seven percent of the patients underwent adjuvant treatment with postoperative radiotherapy (n=160) or chemotherapy (n=21). The indications for adjuvant treatment remained stable throughout the study period: locally advanced tumours (pT3-T4), with positive or close margins, with more than 2 metastatic lymph nodes in the neck dissections (pN2) or the presence of a lymph node with a ruptured capsule.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The percentage was analysed of patients with occult lymph node metastases (cN0/pN+), with lymph node metastases without ENE (pN+/EEN−) or with lymph node metastases with ENE (pN+/EEN+).</p><p id="par0070" class="elsevierStylePara elsevierViewall">The relationship between the presence of occult lymph node metastases and of enlarged lymph nodes with ENE was evaluated with variables such as the location, local extension of the tumour or histological grade. The prognostic impact of lymph node status on local, regional and remote control of the disease was studied, as well as disease-specific survival. Finally the prognostic capacity of TNM classification was evaluated comparing the seventh and the eighth editions.</p><p id="par0075" class="elsevierStylePara elsevierViewall">The Chi-squared or Fisher's exact test were used to compare the qualitative variables. The actuarial method of Kaplan–Meier was used for the survival calculations. The log-rank test was used to compare between the survival curves. A multivariate study was undertaken using Cox proportional-hazards model.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">Thirty-three percent of the patients had occult metastatic lymph nodes in the neck dissections undertaken (cN0/pN+). Of the 115 cN0/pN+ patients, 61 (53%) had only one metastatic neck node, 37 (32%–3%) had more than one unilateral metastastic neck node, and 17 (14.8%) had bilateral or contralateral adenopathies. All of the adenopathies were small in size, under 3<span class="elsevierStyleHsp" style=""></span>cm.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Twenty-three point five percent % (27 pN+/ENE+patients) of cN0/pN+ patients had at least one metastatic neck node with ENE. There were significant differences in the percentage of patients with ENE according to the regional extension of the disease (Fisher's exact test, <span class="elsevierStyleItalic">P</span>=.01). The percentage of cN0/pN+ patients with ENE in the case of the patients with a single metastatic lymph node (n=61) was 13.1%; for the patients with more than one ipsilateral metastatic lymph node (n=37) it was 32.4%; finally for the patients with bilateral or contralateral metastatic lymph nodes (n=17) it rose to 41.2%. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the percentage of patients with occult metastatic neck nodes (cN0/pN+) and with extranodal extension (pN+/ENE+) according to the location of the primary tumour, the category of local extension or the histological grade. The percentage of patients with occult metastatic neck nodes was higher for the more extensive and more poorly differentiated tumours. There was a tendency for the patients with tumours located in the hypopharynx to have a higher percentage of lymph node metastasis with ENE.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">There were significant differences in survival according to node status (<span class="elsevierStyleItalic">P</span>=.0001). Disease-specific survival at 5 years for the cN0/pN0 patients was 90% (95%CI 85.9–94.1), for the cN0/pN+/ENE− patients with metastatic neck nodes with no rupture, it was 71.2% (95% CI 61.3–81.1), and for the cN0/pN+/EEN+ patients with capsular rupture it reduced to 25.9% (95% CI 7.3–44.5). <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the survival curves adjusted for the patients included in the study according to neck node status.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the local, regional and remote recurrence-free survival at 5 years according to nodal status. A gradual reduction in local, regional and remote recurrence-free survival rates was observed as the grade of metastatic lymph node involvement increased (cN0/pN0 versus cN0/pN+/ENE− versus cN0/pN+/ENE+).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> shows the result of a multivariate study that looked at disease-specific survival as the dependent variable and the location of the primary tumour, histological grade, category of local extension of the tumour and the pathological status of the neck dissections as independent variables. According to the multivariate model, the variable that related most significantly with disease-specific survival was the presence of metastatic neck nodes with ENE. Considering cN0/pN0 patients as the benchmark category, the pN+/ENE+ patients had a 10.5 times higher risk of dying as a consequence of the progression of the disease (95%CI 5.7–19.2; <span class="elsevierStyleItalic">P</span>=.0001). The patients with occult metastatic neck nodes without ENE also had a poorer survival rate, although in this case the increase in risk was lower (OR 3.0; 95% CI 1.8–5.0; <span class="elsevierStyleItalic">P</span>=.0001).</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">When the classification criteria of the eighth edition of the TNM were applied, an increase occurred in the pN category in 7.7% of the total number of patients. Of those classified as pN1 according to the seventh edition of the TNM (n=61), 13.1% (n=8) went to pN2a; and of the patients classified as pN2 according to the seventh edition of the TNM (n=54), 35.2% (n=19) went to pN3b. <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows the disease-specific survival curves according to classification of the seventh and eighth editions of the TNM. Based on the inclusion of ENE as a classification criterion, the eighth edition of the TNM enabled a group of patients with a very poor prognosis, included in the pN3b category, to be identified.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">It is currently accepted that the presence of neck nodes with ENE in HNSCC is a marker of biologically aggressive disease,<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">15</span></a> and it is considered one of the prognostic factors that most influences the likelihood of survival, locoregional recurrence and metastasis.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The prevalence of patients with pathological lymph nodes with ENE varies according to the studies consulted, from between 23%<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">16</span></a> and 60%.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">17</span></a> These differences are explained by the lack of homogeneity of the different series in terms of the oncological characteristics of the patients analysed and the location of the primary tumour or the proportion of tumours at advanced stages. Furthermore, the lack of uniform histopathological criteria is also a source of variability in the prevalence of ENE. In a meta-analysis published by Dünne et al.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">18</span></a> 104 publications were rejected from a total of 115 because it was considered that the concept of ENE had not been appropriately defined, clearly highlighting the problem of heterogeneity in its definition. Carter et al.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">19</span></a> outlined the need to define the concept of ENE more precisely, indicating that the different criteria used in previous studies could be conceptualised as part of a continuum of the biological process of neoplastic extranodal extension, namely: capsular invasion, pericapsular oblique extranodal extension, microscopic extracapsular extension, macroscopic extracapsular extension and, finally, macroscopic extracapsular extension with invasion of adjacent structures.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Similarly, Wenzel and Koch<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">20</span></a> defined 7 types within the spectrum of nodal extension: (1) intranodal growth; (2) intranodal growth in contact with the capsule; (3) infiltration of the capsule; (4) capsular desmoplastic reaction; (5) capsular rupture; (6) extracapsular spread in adipose tissue, and (7) carcinomatous lymphangitis.</p><p id="par0125" class="elsevierStylePara elsevierViewall">As an illustration of this process, Noone et al.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">21</span></a> reported 70% survival at 5 years in patients with metastatic neck nodes with no ENE or capsular invasion, which decreased to 48% in patients with metastatic lymph nodes with capsular invasion, and to 27% in patients with ENE. Along the same lines, the papers by Annyas et al.,<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">22</span></a> Zoller et al.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">23</span></a> and Jose et al.,<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">24</span></a> published in the 1970s and 80s, found a higher survival rate in patients with metastatic adenopathies and the presence of ENE. The groups of Johnson et al.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">3</span></a> and Hirabayashi et al.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">16</span></a> found no differences in survival between the pN0 patients and the pN+/ENE− patient, in that the reduction of the survival of pN+patients appeared at the expense of patients with ENE, irrespective of lymph node status.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Many of the abovementioned papers found a relationship between the size of the adenopathy and the likelihood of finding ENE<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">3,16,25</span></a>: the larger the metastatic neck node, the greater the likelihood of finding ENE. However, it is often possible to find ENE in small lymph nodes. Ghadjar et al.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">26</span></a> studied 431 metastatic neck nodes from 133 neck dissections, and found that the mean diameter of the nodes without ENE was 9<span class="elsevierStyleHsp" style=""></span>mm, and 11<span class="elsevierStyleHsp" style=""></span>mm for those with ENE; this difference is statistically significant (<span class="elsevierStyleItalic">P</span>=.0002). Nonetheless, this difference is considered clinically irrelevant and minimises the importance of lymph node size as a predictive factor of the presence of ENE. Of the total positive lymph nodes of less than 1<span class="elsevierStyleHsp" style=""></span>cm (n=220), 48% had ENE, while 29% of the nodes that were less than 5<span class="elsevierStyleHsp" style=""></span>mm (n=59) had ENE.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Irrespective of the tumour volume and load in the neck nodes, the existence of ENE is associated with biological factors related to aggressive behaviour of the tumour, such as the overexpression of inducible nitric oxide synthase,<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">27</span></a> metalloproteinase-12,<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">28</span></a> SERPINE-1<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">29</span></a> or podoplanin.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">30</span></a> Wang et al.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">31</span></a> identified a genetic signature based on the expression of 11 genes that enabled ENE to be established in HNSCC patients.</p><p id="par0140" class="elsevierStylePara elsevierViewall">All the above mentioned studies evaluated patients with different grades of regional clinical spread (cN+), confirmed pathologically. However, there are few publications on the prognostic implication of ENE in patients who are free from clinical regional involvement during the initial workup (cN0). Clinical and radiological examination negative for lymph node spread in any event implies the existence of small metastatic adenopathies, with no fixation or loss of margin definition, alteration of the adjacent fat planes or central necrosis. The peculiarities of this subgroup imply that the presence of ENE does not necessarily reduce the possibilities of survival, since these are patients with a very low regional tumour load.</p><p id="par0145" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a> shows the percentages of patients with occult metastatic neck nodes (cN0/pN+) and with extranodal extension (cN0/pN+/ENE+) in series analysed by different authors. There is a marked variability in the percentage of patients with occult metastatic neck nodes with ENE, ranging between 6.3<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">32</span></a> and 22.2%.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">34</span></a></p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">According to our results, the incidence of patients with occult metastatic neck nodes in the elective dissections performed on cN0 patients was 33%. Of the patients with occult metastatic neck nodes, 23.5% had at least one metastatic adenopathy with ENE, which is 7.7% of the total number of cN0 patients treated with elective neck dissection. We did not find a relationship between the appearance of occult metastatic neck nodes with ENE and variables such as local spread of the tumour or the degree of differentiation. The patients with tumours located in the hypopharynx had a greater tendency to present occult metastatic neck nodes with ENE, which might be related to the greater biological aggressiveness of these tumours.</p><p id="par0155" class="elsevierStylePara elsevierViewall">In line with the results obtained by Alvi and Johnson<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">33</span></a> and Gourin et al.,<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">35</span></a> the presence of occult metastatic neck nodes with ENE resulted in a significant reduction in survival compared to the patients with metastatic neck nodes without ENE, which dropped from 71.2% for cN0/pN+/ENE− patients to 25.9% for cN0/pN+/EEN+ patients. Furthermore, according to the results of a multivariate study, the presence of occult metastatic neck nodes with ENE was the variable most significantly associated with disease-specific survival, increasing the risk of death as a consequence of the disease more than 10 times that of cN0/pN0 patients.</p><p id="par0160" class="elsevierStylePara elsevierViewall">We observed that the presence of ENE in neck dissections, in addition to being associated with an increased risk of regional recurrence and remote metastases, appeared to be associated with a significant increase in the incidence of local recurrences. This association between ENE and deterioration in local control of the disease has been described by other authors,<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">36,37</span></a> who relate the greater infiltrative capacity of tumours with neck nodes with ENE with greater aggressiveness and resistance to treatment.</p><p id="par0165" class="elsevierStylePara elsevierViewall">The eighth edition of the TNM<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">13</span></a> includes the presence of ENE as a criterion for the histopathological classification of pN. According to this new edition of the TNM, the presence of lymph node metastases with ENE implies increasing a level in the regional involvement category, so that patients classified as pN1 in the seventh edition<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">12</span></a> become pN2a, and those classified as pN2 become pN3b. The results of our study indicate that applying the classification criteria of the eighth edition of the TNM improves prognostic capacity in the histopathological evaluation of neck dissections in patients with a low neck tumour load, classified as cN0 at the initial clinical assessment of the tumour. This improved prognostic capacity is basically at the expense of patients classified as pN2 with the seventh edition of the TNM. On applying the criteria of the eighth edition, a group with a poor prognosis with ENE was identified who were then classified as pN3b, and another group of patients without ENE with a better prognosis remained in the pN2 category.</p><p id="par0170" class="elsevierStylePara elsevierViewall">One of the present study's limitations is that it does not include information on the degree of infiltration of the node capsule and the tissue surrounding the nodes. As a consequence, we were not able to establish differences in prognosis based on the level of peri-nodal involvement. However the study includes a large series of consecutive patients, with no history of previous regional treatment, with a long follow-up period, which establishes the consistency of our findings.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0175" class="elsevierStylePara elsevierViewall">Our results confirm the importance of ENE as a prognostic marker in the group of patients with occult neck node disease, considered cN0 on initial evaluation of the tumour. The inclusion of ENE as a criterion for histopathological classification in the eighth edition of the TNM is an improvement on the prognostic capacity of previous editions.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0180" class="elsevierStylePara elsevierViewall">This study was financed with a grant from the National Plan for R&D&I of the Carlos III Institute of Health (co-financed by the European Regional Development Fund – FEDER, A Way to Build Europe; FIS 14-01819 to XL).</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of Interests</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1025748" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec983480" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1025749" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec983481" "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" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of Interests" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-02-20" "fechaAceptado" => "2017-07-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec983480" "palabras" => array:5 [ 0 => "Squamous cell carcinoma of the head and neck" 1 => "Occult neck node metastases" 2 => "Extranodal extension" 3 => "CN0" 4 => "Elective neck dissection" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec983481" "palabras" => array:5 [ 0 => "Carcinoma escamoso de cabeza y cuello" 1 => "Metástasis ganglionar oculta" 2 => "Extensión extranodal" 3 => "CN0" 4 => "Vaciamiento cervical electivo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Extranodal extension in nodal metastases is an independent adverse prognostic factor in head and neck squamous cell carcinoma patients. However, few studies specifically address the subgroup of patients with no clinical evidence of nodal disease.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We retrospectively analysed data from 348 head and neck squamous cell carcinoma patients without any previous treatment and lacking clinical or radiological evidence of neck node metastases during the initial workup, treated with an elective neck dissection between 1992 and 2014. The incidence of occult metastatic neck nodes with extranodal extension and the impact of extranodal extension in survival were evaluated.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The proportion of patients with occult neck node metastases was 33%. Of these, 23.5% had at least one metastatic neck node with extranodal extension. There were significant differences in the disease-specific survival rate according to neck node status. Five-year disease-specific survival for patients without histopathological metastases was 90%, for patients with occult neck node metastases without extranodal extension it was 71.2%, and for patients with occult neck node metastases with extranodal extension it was 25.9% (<span class="elsevierStyleItalic">P</span>=.0001). The multivariate analysis revealed that the presence of occult node metastases with extranodal extension was the factor with strongest impact on survival. The inclusion of the extranodal extension as a criterion of histopathological evaluation in the 8th TNM classification edition improves the prognostic capacity compared to previous TNM editions.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Appearance of metastatic neck nodes with extranodal extension is an adverse prognostic factor in head and neck squamous cell carcinoma patients without clinical evidence of regional disease during the initial workup of the tumour.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La presencia de extensión extranodal en adenopatías metastásicas de pacientes con carcinoma escamoso de cabeza y cuello es un reconocido factor de mal pronóstico. Sin embargo, pocos estudios analizan específicamente su significado en pacientes sin evidencia clínica de extensión ganglionar en el momento del diagnóstico inicial.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo de 348 pacientes con carcinoma escamoso de cabeza y cuello cN0 tratados con un vaciamiento cervical electivo. Se evaluó la presencia de metástasis ganglionares ocultas con extensión extranodal y se analizó su impacto sobre la supervivencia.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El porcentaje de pacientes con metástasis ganglionares ocultas fue del 33%. De estos, un 23,5% presentaron al menos una adenopatía metastásica con extensión extranodal. Existieron diferencias significativas en la supervivencia específica en función del estatus ganglionar. La supervivencia a los 5 años para los pacientes sin afectación ganglionar patológica fue del 90%, para aquellos con metástasis ganglionares ocultas sin extensión extranodal, del 71,2%, y para los pacientes con metástasis ganglionares ocultas con extensión extranodal, del 25,9% (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,0001). En un estudio multivariante la presencia de metástasis ganglionares ocultas con extensión extranodal fue el factor relacionado de forma más importante con la supervivencia. La incorporación de la extensión extranodal como criterio de clasificación histopatológico en la octava edición del TNM mejoró la capacidad pronóstica en relación con las ediciones anteriores.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La presencia de adenopatías metastásicas con extensión extranodal es un factor de mal pronóstico en pacientes con carcinoma escamoso de cabeza y cuello sin evidencia clínica de afectación regional en el momento del diagnóstico de la enfermedad.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Lop J, Rigó A, Codina A, de Juan J, Quer M, León X. Significado pronóstico de la extensión extranodal en pacientes con carcinomas escamosos de cabeza y cuello cN0 con metástasis ganglionares ocultas. Acta Otorrinolaringol Esp. 2018;69:156–164.</p>" ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 989 "Ancho" => 1529 "Tamanyo" => 75947 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Disease-specific survival for patients with no occult metastatic neck nodes (cN0/pN0), with occult metastatic neck nodes with no extranodal extension (cN0/pN+/ENE−) and with occult metastatic neck nodes with extranodal extension (cN0/pN+/ENE+).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2185 "Ancho" => 1527 "Tamanyo" => 147528 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Disease-specific survival according to the seventh and eighth editions of TNM classification of malignant tumours.</p>" ] ] 2 => 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" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ENE: extranodal extension.</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>: Sobin et al.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">12</span></a> and Brierley et al.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">13</span></a></p>" "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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TNM, seventh edition \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TNM, eighth edition \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pN1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastasis in a single ipsilateral node 3<span class="elsevierStyleHsp" style=""></span>cm or less \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">pN1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastasis in a single ipsilateral node 3<span class="elsevierStyleHsp" style=""></span>cm or less without ENE \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pN2a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastasis in a single ipsilateral node larger than 3<span class="elsevierStyleHsp" style=""></span>cm but no larger than 6<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">pN2a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastasis in a single ipsilateral node larger than 3<span class="elsevierStyleHsp" style=""></span>cm but not larger than 6<span class="elsevierStyleHsp" style=""></span>cm, without EEN<br>Metastasis in a single ipsilateral node of 3<span class="elsevierStyleHsp" style=""></span>cm or less with EEN \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pN2b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastases in multiple homolateral nodes, none larger than 6<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">pN2b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastases in multiple homolateral nodes, none larger than 6<span class="elsevierStyleHsp" style=""></span>cm, without ENE \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pN2c \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastases in bilateral or contralateral nodes, non larger than 6<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">pN2c \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastases in bilateral or contralateral nodes, none larger than 6<span class="elsevierStyleHsp" style=""></span>cm, without ENE \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pN3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastasis in one node larger than 6<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">pN3a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastasis in one node larger than 6<span class="elsevierStyleHsp" style=""></span>cm, without ENE \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">pN3b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastases in a single ipsilateral node larger than 3<span class="elsevierStyleHsp" style=""></span>cm, with ENE<br>Metastases in multiple ipsilateral, contralateral or bilateral nodes, at least one with ENE \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1745253.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparison of the Classification Criteria of the Node Category Between the Seventh and Eighth Editions of TNM.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">13</span></a></p>" ] ] 3 => 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: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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Sex</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">298 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Age in years, mean (range)</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">63.6 (32.8–91.6)</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="5" align="left" valign="top">Location</td><td class="td" title="table-entry " align="left" valign="top">Oral cavity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">123 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oropharynx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypopharynx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Supraglottis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glottis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">116 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">Local spread</td><td class="td" title="table-entry " align="left" valign="top">T1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">134 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Differentiation</td><td class="td" title="table-entry " align="left" valign="top">Good \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">270 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">77.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Poor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1745249.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Features of the Patients Included in the Study.</p>" ] ] 4 => 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" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">cN0/pN+: occult metastatic neck nodes; pN+/ENE+: occult metastatic neck nodes with extranodal extension.</p>" "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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">cN0/pN+, % \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">pN+/ENE+, % \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="5" align="left" valign="top">Location</td><td class="td" title="table-entry " align="left" valign="top">Oral cavity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="5" align="left" valign="top">.8</td><td class="td" title="table-entry " align="char" valign="top">5.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="5" align="left" valign="top">.05</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oropharynx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypopharynx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Supraglottis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glottis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Local extension</td><td class="td" title="table-entry " align="left" valign="top">T1-2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">.04</td><td class="td" title="table-entry " align="char" valign="top">6.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">.4</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3-4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Differentiation</td><td class="td" title="table-entry " align="left" valign="top">Good \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="top">.2</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Poor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1745250.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Percentage of Patients With Occult Metastatic Neck Nodes and With Extranodal Extension According to the Location, Extension and Histological Grade of the Primary Tumour.</p>" ] ] 5 => 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" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">cN0/pN0: clinical and histological absence of nodal metastases; cN0/pN+/EEN−: presence of occult metastatic neck nodes without extranodal extension; 95% CI: 95% confidence interval; pN+/ENE+: presence of occult metastatic neck nodes with extranodal extension; rN: regional recurrence; rM: remote recurrence rT: local recurrence.</p>" "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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">rT (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">rN (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">rM (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">cN0/pN0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">94.4% (61.3–97.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">96.8% (94.5–99.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95.2% (92.3–98.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">cN0/pN+/ENE− \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80% (70.8–89.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90.2% (83.2–97.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">86.2% (78.6–93.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">cN0/pN+/ENE+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52.7% (28.4–77.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">78.4% (59.4–97.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48.8% (23.8–73.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1745254.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Local, Regional or Remote Recurrence-Free Survival According to Lymph Node Status.</p>" ] ] 6 => 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" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">95% CI: 95% confidence interval; OR: odds ratio; pN+/ENE−: occult metastatic neck nodes without extranodal extension; pN+/ENE+: occult metastatic neck nodes with extranodal extension.</p>" "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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95% CI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="5" align="left" valign="top">Location</td><td class="td" title="table-entry " align="left" valign="top">Oral cavity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oropharynx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.05–4.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.035 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypopharynx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.62–2.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.443 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Supraglottis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.18–.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.021 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glottis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.36–1.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.272 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Differentiation</td><td class="td" title="table-entry " align="left" valign="top">Good \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.60–2.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.644 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Poor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.74–2.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.490 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Local extension</td><td class="td" title="table-entry " align="left" valign="top">T1-2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3-4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.49–4.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Neck node status</td><td class="td" title="table-entry " align="left" valign="top">pN0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pN+/ENE− \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.81–5.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pN+/ENE+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.70–19.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1745251.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Result of a Multivariate Analysis That Examined Specific Survival as a Dependent Variable.</p>" ] ] 7 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at6" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">cN0/pN+: occult metastatic neck nodes; pN+/EEN+: occult metastatic neck nodes with extranodal extension.</p>" "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"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">cN0/pN+, n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">pN+/ENE+, n (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pinsolle et al.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">31</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">171 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 (28.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 (10.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Snyderman et al.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 (40.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (20.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">De Carvalho<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">32</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 (22.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (6.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alvi and Johnson<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">33</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">109 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 (33.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 (16.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Coatesworth and MacLennan<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">34</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 (30.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (22.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gourin et al.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">35</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">337 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">168 (49.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lop \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">348 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">115 (33.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 (7.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1745252.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">cN0 With Occult Metastatic Neck Nodes and With Occult Metastatic Neck Nodes With Extranodal Extension in Different Published Series.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:37 [ 0 => array:3 [ "identificador" => "bib0190" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidermoid carcinoma of the head and neck, with special reference to metastasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.A. 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Prognostic Significance of Extranodal Extension in Head and Neck Squamous Cell Carcinoma cN0 Patients With Occult Metastatic Neck Nodes
Significado pronóstico de la extensión extranodal en pacientes con carcinomas escamosos de cabeza y cuello cN0 con metástasis ganglionares ocultas