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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Series of EBUS images of the mediastinal lymph node showing the different criteria &#40;<span class="elsevierStyleItalic">continued</span>&#41;&#46; &#40;A&#41; Presence of central hilar structure &#40;arrow&#41; in reactive lymph node&#46; &#40;B and C&#41; Presence of central hilar structure with blood vessel &#40;arrow&#41; in another reactive lymph node&#59; demonstration in Doppler mode in &#40;C&#41;&#46; &#40;D&#41; Indistinct margin with heterogeneous echogenicity in extrathoracic metastasis with the absence of central hilar structure&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Lymph node &#40;LN&#41; biopsy is essential for accurate staging of lung cancer&#46; Endobronchial ultrasound &#40;EBUS&#41; is a technique that combines endoscopic visualization with high frequency ultrasound imaging&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> EBUS is useful for visualizing both mediastinal and hilar LN<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and for guiding needle aspiration during the cytological and histological biopsy procedure&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In the last decade&#44; many studies have evaluated sonographic observations that may suggest malignant LN infiltration in head and neck&#44; breast&#44; uterine cervix and esophageal cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;6&#8211;9</span></a> In a recent retrospective study in lung cancer&#44; Fujiwara et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> described 4 sonographic features of value for predicting the malignant infiltration of mediastinal LN &#40;round shape&#44; distinct margin&#44; heterogeneous echogenicity and the presence of coagulation necrosis sign&#41;&#46; Schmid-Bindert et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> proposed a score that combined the following ultrasound criteria for predicting malignancy in mediastinal LN&#58; round shape&#44; well-defined margins&#44; echogenicity&#44; the absence of any central hilar structure &#40;CHS&#41;&#44; short axis &#8805;1<span class="elsevierStyleHsp" style=""></span>cm and color power Doppler index grade 2 or 3&#46; The authors concluded that if less than 3 of the specified criteria were present&#44; the LN had a very low probability of being malignant&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> However&#44; these criteria are retrospective and may have a subjective component&#44; since no prospective validation was made and some of the criteria used are difficult for experienced operators to determine in real time&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In an attempt to validate the clinical utility of the foregoing criteria&#44; the hypothesis was proposed that some LN ultrasound criteria could be useful for predicting malignant LN infiltration and thus could be used as a guide for selecting LNs for aspiration&#44; leading to improved bronchogenic staging&#46; Consequently&#44; the objectives of this study were&#44; firstly&#44; to evaluate retrospectively which EBUS sonographic features were the most accurate for differentiating benign involvement from malignant involvement in both mediastinal and hilar LNs&#44; after correlating these features with the histopathological results&#59; and secondly&#44; to prospectively analyze the previously proposed score for a combination of these ultrasound criteria for real-time clinical application&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design and study patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">The study was divided into 2 parts&#46; The first was a descriptive study for which 176 patients with mediastinal&#47;hilar LN undergoing EBUS in the Hospital Universitario Son Espases between 2009 and 2012 for lung cancer staging or investigation of suspected malignant LN infiltration were screened&#46; Of these patients&#44; 141 were included in the study&#44; and 2 raters who were unaware of the final diagnosis independently analyzed the 208 LN images&#46; The second part was a prospective study for which 39 consecutive patients were recruited and two raters predicted the probability of malignant LN involvement in real time on the basis of the previously validated criteria&#46; Consecutive patients scheduled to undergo EBUS to study mediastinal&#47;hilar LN observed on a computed tomography &#40;CT&#41; of the chest or hypermetabolic LN identified in a positron emission tomography with fluorodeoxyglucose &#40;PET-FDG&#41; were included&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The indication for performing invasive mediastinum staging by EBUS&#44; endoscopic ultrasound &#40;EUS&#41;&#44; or a combination of both techniques is established by a local multidisciplinary lung cancer committee&#44; according to the following standardized criteria<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#58; &#40;a&#41; enlarged discrete mediastinal LN with PET uptake&#59; &#40;b&#41; PET activity in a mediastinal LN and nodes with normal appearance on CT&#44; and &#40;c&#41; suspected N2&#44;3 involvement with a radiographically normal mediastinum &#40;determined by CT and PET&#41; and a central or N1 tumor&#46; Patients with any contraindication for bronchoscopy according to the recommendations of the American Thoracic Society<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> or a high anesthetic risk &#40;American Society of Anesthesiologists physical status &#62;3&#41;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> were excluded&#46; A full clinical history was obtained and chest CT and PET-FDG images were analyzed by a multidisciplinary lung cancer committee that established the indication for performing EBUS with transbronchial needle aspiration &#40;TBNA&#41; or transtracheal aspiration &#40;TTA&#41;&#44; following international guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Patients were then evaluated by the anesthesiology team before the intervention&#46; Informed consent was obtained from all patients&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">EBUS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TTA&#47;TBNA procedure</span><p id="par0030" class="elsevierStylePara elsevierViewall">EBUS was performed using an EB-1970UK &#40;Pentax&#44; 10&#46;0-5&#46;0<span class="elsevierStyleHsp" style=""></span>MHz&#44; Tokyo&#44; Japan&#41; endoscope and the Hitachi Digital Ultrasound Scanner EUB-7000HV&#46; The procedure was performed via the oral route under deep sedation with propofol&#44; midazolam and fentanyl with anesthesiologist-controlled spontaneous ventilation in all study patients&#46; The intervention was performed as described by Yasufuku et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Enlarged LNs &#40;greater than 5<span class="elsevierStyleHsp" style=""></span>mm&#41; were identified by the measurements made in the digitally captured ultrasound images&#46; Fixed images were captured for subsequent analysis&#46; Blood vessels were confirmed with the Doppler modality&#46; For TBNA and&#47;or TTA&#44; a 22-caliber needle was used&#46; The needle was introduced via the working channel of the EBUS through the bronchial wall&#44; and the LN was aspirated under ultrasound guidance to obtain a tissue biopsy&#46; A smear of the aspirated material was prepared on a glass slide&#44; air-dried and immediately stained with standard hematoxylin and eosin for rapid on-site evaluation &#40;ROSE&#41; by a cytopathologist&#46; Three consecutive biopsies of a reactive LN were considered negative for malignant disease&#46; The aspirated materials were also collected in liquid formol&#44; and the cell block underwent a final histological evaluation by the pathologist&#46; The final pathological diagnosis was the standard reference for positive malignant LN infiltration&#46; Patients with negative pathology results on EBUS in whom malignant LNs were confirmed after surgery &#40;mediastinoscopy or lung resection with systematic lymphadenectomy&#41; were also considered positive in the sonographic analysis of the LNs&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Analysis of ultrasound images</span><p id="par0035" class="elsevierStylePara elsevierViewall">All ultrasound images were evaluated to determine the foregoing sonographic features<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> with the aim of validating a score predictive of malignancy&#46; The following sonographic features associated with malignity were evaluated<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Round shape&#44; defined as a ratio of &#60;1&#46;5 between 2 perpendicular axes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Distinct and well defined&#44; distinguished by a marked white line delimiting the LN&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Appearance of heterogeneous echogenicity as a dichotomous variable &#40;as opposed to homogeneous&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Absence of visible CHS in the form of a central linear structure with high echogenicity&#44; with or without a blood vessel&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Small axis &#8805;10<span class="elsevierStyleHsp" style=""></span>mm&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#46;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Hyperechogenic density in the interior of the LN &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></li></ul></p><p id="par0070" class="elsevierStylePara elsevierViewall">The interrater agreement &#40;IRA&#41; was calculated for each sonographic criteria&#46; These criteria were correlated with the final histopathological results&#44; and the sensitivity&#44; specificity and positive and negative predictive values &#40;PPV and NPV&#44; respectively&#41; were calculated from the receiver operating characteristics &#40;ROC&#41; curve and the area under the curve &#40;AUC&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Scoring</span><p id="par0075" class="elsevierStylePara elsevierViewall">According to the reproducibility of the above-mentioned criteria&#44; a simplified 5-item score was generated and calculated for prediction of LN malignancy&#46; Each item was scored as follows&#58; heterogeneous &#40;1&#46;5 points&#41; <span class="elsevierStyleItalic">versus</span> homogeneous &#40;0 points&#41; echogenicity&#59; absence of CHS &#40;1&#46;5 points&#41; <span class="elsevierStyleItalic">versus</span> presence &#40;0 points&#41;&#59; round shape &#40;1 <span class="elsevierStyleItalic">versus</span> 0 points&#41;&#59; small LN axis &#8805;10<span class="elsevierStyleHsp" style=""></span>mm &#40;1 point&#41;&#59; and well-defined LN margin &#40;1 point&#41; <span class="elsevierStyleItalic">versus</span> indistinct margin &#40;0 points&#41;&#46; A total score was generated from the sum of each separate criterion and plotted relative to the pathological diagnosis on ROC curves&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Score validation</span><p id="par0080" class="elsevierStylePara elsevierViewall">The previously modified score was applied prospectively to the ultrasound images of the suspect LN during the EBUS procedure by the two bronchoscopists performing the examination&#46; The sonographic analysis was performed by a pathologist before the ROSE&#46; The score was calculated and correlated with the histopathological results&#46; A Doppler ultrasound was performed to evaluate blood flow within the LN&#46; The utility of the proposed score was evaluated for the prediction of LN malignancy in real-time clinical application&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0085" class="elsevierStylePara elsevierViewall">The data are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41; or number &#40;percentage&#41;&#44; as appropriate&#46; Malignant and non-malignant sonographic features were compared using the Mann&#8211;Whitney test&#46; Statistical tests were performed with two-tailed <span class="elsevierStyleItalic">p</span> values&#44; with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 being considered statistically significant&#46; ROC curves were used to calculate sensitivity and specificity&#44; followed by the calculation of PPV and NPV for the score and for each criterion in relation to the final pathological diagnosis&#46; AUC&#44; C-index values and 95&#37; confidence intervals &#40;CI&#41; are presented&#46; The IRA was calculated using the interval-to-interval method&#44; which is calculated by adding the total number of agreements in the intervals &#40;for both the presence and the absence of malignancy&#41; and dividing by the sum of the number of agreements and discrepancies in the intervals<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#59; an IRA of 80&#37; was considered a positive agreement&#46; MedCalc<span class="elsevierStyleSup">&#174;</span> &#40;version 9&#46;2&#46;1&#46;0&#44; Acacialaan 22&#44; B-8400 Ostend&#44; Belgium&#41; statistical software was used&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Sonographic features</span><p id="par0090" class="elsevierStylePara elsevierViewall">Patient characteristics and principal results are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; After correlation with the pathology data was established&#44; the images obtained from 141 patients&#44; including 208 LNs from various node stations&#44; were analyzed&#46; The subcarinal LN &#40;station 7&#41; was the most frequently aspirated node &#40;45&#46;7&#37;&#41;&#44; followed by stations 4R and 4L &#40;24&#37; and 9&#46;6&#37;&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">A definitive diagnosis of malignant disease in the LNs analyzed was obtained in 50&#46;5&#37; of the subjects compared to 49&#46;5&#37; with reactive lymphadenitis&#46; The final pathology of the biopsies evaluated is presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; showing that adenocarcinoma was the most common diagnosis in the study cohort &#40;22&#46;7&#37;&#41;&#44; followed by squamous cell carcinoma &#40;12&#46;8&#37;&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The analysis of the LN sonographic features&#44; with their corresponding sensitivity&#44; specificity&#44; PPV and NPV for malignant disease&#44; is shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; The evaluation of the different sonographic criteria revealed that both heterogeneous echogenicity and the absence of CHS with or without central blood vessel were the most sensitive factors for predicting malignant disease &#40;99&#37; in both cases&#41;&#44; while hyperechogenic density in the interior of the LN had the highest specificity for predicting malignant LNs &#40;78&#37;&#41;&#46; Moreover&#44; heterogeneous echogenicity showed an NPV of 94&#46;4&#37;&#44; followed by the absence of CHS &#40;90&#37;&#41;&#46; None of the proposed sonographic criteria had a clinically acceptable PPV&#46; A positive IRA for the proposed criteria was recorded&#44; with the maximum agreement being observed for heterogeneous echogenicity &#40;92&#46;2&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The difference between the malignant and non-malignant infiltration of the LN for each criterion was statistically significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; with the exception of the presence of hyperechogenic density in the interior of the LN &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; Consequently&#44; scoring was generated using only 5 criteria&#44; as described above in the methodology section&#46; With the ROC analysis&#44; the combined score of &#62;5 has a sensitivity of 73&#46;3&#37; and a specificity of 68&#37; &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;738&#59; 95&#37; CI&#58; 0&#46;673&#8211;0&#46;796&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; for the prediction of malignant LN infiltration &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The PPV and NPV for the generated score were 70&#37; and 71&#46;4&#37;&#44; respectively&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Prospective validation study</span><p id="par0110" class="elsevierStylePara elsevierViewall">A real-time evaluation of the LNs during EBUS was performed in 39 patients&#44; and 65 LNs were examined during the procedure&#46; The prevalence of malignant disease in the LNs examined was 35&#46;4&#37; and the most common pathological diagnosis was adenocarcinoma &#40;15&#46;4&#37;&#41;&#46; The subcarinal LN was the most frequently aspirated station &#40;46&#46;2&#37;&#41;&#44; followed by station 4R &#40;24&#46;6&#37;&#41; and then station 10R or 10L &#40;18&#46;5&#37;&#41;&#46; Stations 4L&#44; 2R and 2L represented 7&#46;7&#37;&#44; 1&#46;5&#37; and 1&#46;5&#37; of the aspirations&#44; respectively&#46; When the previously validated sonographic criteria were applied in real time&#44; the absence of CHS&#44; a round shape and a short axis &#8805;10<span class="elsevierStyleHsp" style=""></span>mm yielded significantly statistical differences between non-malignant and malignant LNs &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0012&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;012 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;023&#44; respectively&#41;&#46; Neither heterogeneous echogenicity nor a distinct margin showed a statistically significant difference between benign and malignant LNs &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; as indicated in the retrospective analysis of the ultrasound images&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">With the combination of positive criteria during the procedure&#44; a score of &#62;5 was found to have a sensitivity of 78&#37; and specificity of 86&#37; in the detection of a malignant LN &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;852&#59; 95&#37; CI&#58; 0&#46;743&#8211;0&#46;928&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; with a greater specificity than that obtained from the analysis of images&#46; PPV and NPV were 75&#37; and 88&#37;&#44; respectively&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">EBUS-TBNA has been welcomed in clinical practice as an effective instrument for lung cancer staging with an accuracy comparable to that of surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#8211;20</span></a> However&#44; systematic aspiration of all LNs by EBUS-TBNA is a lengthy and expensive procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> For this reason&#44; the need for sonographic criteria to serve as a guide for obtaining biopsies from the various LN stations has been identified&#46; This study has shown that no single criterion is sufficiently specific&#44; but a combination of different sonographic criteria may be useful for predicting malignancy in mediastinal LNs&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;8&#44;10&#44;11</span></a> and this combination of criteria may be valid for real-time clinical application&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Sonographic criteria for the prediction of malignant LN infiltration in lung cancer have already been analyzed retrospectively in various studies in EBUS or EUS&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;10&#44;11</span></a> Fujiwara et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> defined 4 different criteria for predicting malignancy in LNs&#44; with a diagnostic accuracy of between 63&#46;8&#37; and 86&#46;0&#37; for malignant LNs&#46; In a similar study&#44; Gill et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> explored mediastinal LNs in cases of primary lung cancer using EUS&#59; these authors found that only a round shape&#44; short axis &#62;8&#46;3<span class="elsevierStyleHsp" style=""></span>mm and distinct margins were associated with malignant LN infiltration&#46; More recently&#44; Schmid-Bindert et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> studied mediastinal lymphadenopathies&#44; irrespective of underlying disease&#44; and established a scoring system based on the sum of 6 positive criteria suggestive of LN malignancy&#59; they described a high probability of malignant disease if the score was &#8805;3&#46; They also found that heterogeneous echogenicity and the absence of CHS provided better NPV&#46; These results coincide with the data presented here&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In this study&#44; 5 criteria for LN malignancy were selected for their simplicity&#44; making them suitable for use in real-time situations&#46; Although none of them in isolation was sufficiently specific for differentiating malignancy&#44; as was also found in earlier studies&#44; a score of &#62;5 was associated with acceptable accuracy in terms of sensitivity and specificity in the retrospective analysis&#46; In line with previously obtained results&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> heterogeneous echogenicity and the absence of CHS were the most sensitive factors in predicting LN malignancy &#40;99&#37;&#41; and provided the best NPV &#40;94&#46;4&#37; and 90&#37;&#44; respectively&#41;&#46; It is interesting to observe that the real-time application of these criteria during the EBUS procedure improved both the sensitivity and the specificity of a score of &#62;5 for predicting LN malignancy by 78&#46;3&#37; and 86&#37;&#44; respectively&#46; Moreover&#44; the absence of CHS&#44; the shape and the diameter of the short axis &#8805;10<span class="elsevierStyleHsp" style=""></span>mm were significantly different for non-malignant and malignant infiltration&#46; However&#44; heterogeneous echogenicity and a distinct margin showed no significant correlation during real-time evaluation&#44; compared to the previous image analysis observations&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">A retrospective analysis of the ultrasound images showed that the presence of hyperechogenic density in the interior of the LN was the most specific sign of malignancy&#44; but sensitivity was low&#44; probably due to its low incidence&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Consequently&#44; this criterion was not included in the combined scoring system&#46; The unacceptable PPV of current criteria reviewed may be due&#44; in part&#44; to the relatively low prevalence of malignant LN infiltration in our cohort&#46; A score of &#62;5&#44; meanwhile&#44; was found to have the greatest sensitivity and specificity&#44; and this may have several explanations&#58; firstly&#44; there is no single acceptable sonographic criterion for predicting LN malignancy<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#59; secondly&#44; no malignant lymphadenopathies&#44; including reactive LN&#44; with a diameter of &#8805;10<span class="elsevierStyleHsp" style=""></span>mm and the absence of CHS on ultrasound have been described&#44;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> indicating that these two features are non-specific for malignant LN infiltration&#46; This raised the problem&#44; discussed by previous authors&#44; of basing prediction of malignant LN infiltration on only three positive criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The coagulation necrosis sign<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> was not observed in our retrospective analysis&#44; and the grade of blood flow to the interior of the LN<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> was not feasible for simplified application in a clinical setting&#44; and only achieved moderate agreement among the different raters&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and as such was not included in the criteria evaluated&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">This study has certain limitations&#46; Firstly&#44; measurement of the LN axis is subjective<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> and depends on manipulation of the EBUS transducer for obtaining the maximum LN diameters&#46; Secondly&#44; biopsies could not be obtained for all LNs detected during the EBUS procedure due to the proximity of blood vessels or difficulty in introducing the needle through the walls of the airway due to&#44; for example&#44; fibrosis or malignant infiltration of the wall itself&#46; Thirdly&#44; EUS was not used in this study&#46; A combination of EUS-guided fine needle aspiration &#40;EUS-FNA&#41; and EBUS-TBNA is recommended for full evaluation of mediastinal LNs&#46; This provides greater sensitivity and NPV than those obtained with each technique used alone&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> However&#44; a recent randomized controlled trial looking at diagnostic accuracy has shown that the addition of EUS-FNA to EBUS-TBNA did not improve accuracy or sensitvity&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">To conclude&#44; the selected criteria &#40;round shape&#44; distinct margin&#44; heterogeneous echogenicity&#44; the absence of CHS&#44; and short axis &#8805;10<span class="elsevierStyleHsp" style=""></span>mm&#41; are reliable for real-time clinical application&#46; A score of &#62;5 showed good prediction for malignant LN and may be useful for taking decisions regarding LN sampling during the procedure&#46; Moreover&#44; there is no single criterion that can be used to rule out malignant infiltration of mediastinal or hilar LN&#59; however&#44; the absence of CHS&#44; a round shape and an increased LN axis are suggestive of LN malignancy&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interests</span><p id="par0150" class="elsevierStylePara elsevierViewall">Hanaa Shafiek has received grants from the <span class="elsevierStyleGrantSponsor" id="gs1">University of Alexandria</span> and the <span class="elsevierStyleGrantSponsor" id="gs2">Egyptian Ministry of Upper Education</span>&#44; as member of ParOwn &#40;The Partnership and Ownership Initiative&#41;&#46; The other authors have no conflict of interests&#46;</p></span></span>"
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        0 => array:2 [
          "identificador" => "xres342983"
          "titulo" => array:5 [
            0 => "Abstract"
            1 => "Objective"
            2 => "Methods"
            3 => "Results"
            4 => "Conclusions"
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        1 => array:2 [
          "identificador" => "xpalclavsec324620"
          "titulo" => "Keywords"
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          "identificador" => "xres342982"
          "titulo" => array:5 [
            0 => "Resumen"
            1 => "Objetivo"
            2 => "M&#233;todos"
            3 => "Resultados"
            4 => "Conclusiones"
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          "identificador" => "xpalclavsec324619"
          "titulo" => "Palabras clave"
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          "titulo" => "Introduction"
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        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Methods"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Design and study patients"
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            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "EBUS &#43; TTA&#47;TBNA procedure"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Analysis of ultrasound images"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Scoring"
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            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Score validation"
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              "identificador" => "sec0040"
              "titulo" => "Statistical analysis"
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          "identificador" => "sec0045"
          "titulo" => "Results"
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            0 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Sonographic features"
            ]
            1 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Prospective validation study"
            ]
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        7 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Discussion"
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        8 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Conflict of interests"
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        9 => array:1 [
          "titulo" => "References"
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    "tienePdf" => true
    "fechaRecibido" => "2013-09-21"
    "fechaAceptado" => "2013-12-16"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec324620"
          "palabras" => array:3 [
            0 => "Endobronchial ultrasound"
            1 => "Mediastinal lymph node"
            2 => "Lung cancer staging"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec324619"
          "palabras" => array:3 [
            0 => "Ecograf&#237;a endobronquial"
            1 => "Ganglio linf&#225;tico mediast&#237;nico"
            2 => "Estadificaci&#243;n de c&#225;ncer de pulm&#243;n"
          ]
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To evaluate the utility of different ultrasonographic &#40;US&#41; features in differentiating benign and malignant lymph node &#40;LN&#41; by endobronchial ultrasound &#40;EBUS&#41; and validate a score for real-time clinical application&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A total of 208 mediastinal LNs acquired from 141<span class="elsevierStyleHsp" style=""></span>patients were analyzed&#46; Six different US criteria were evaluated &#40;short axis &#8805;10<span class="elsevierStyleHsp" style=""></span>mm&#44; shape&#44; margin&#44; echogenicity&#44; central hilar structure &#91;CHS&#93;&#44; and presence of hyperechoic density&#41; by two observers independently&#46; A simplified score was generated where the presence of margin distinction&#44; round shape and short axis &#8805;10<span class="elsevierStyleHsp" style=""></span>mm were scored as 1&#44; and heterogeneous echogenicity and absence of CHS were scored as 1&#46;5&#46; The score was evaluated prospectively for real-time clinical application in 65 LNs during EBUS procedure in 39<span class="elsevierStyleHsp" style=""></span>patients undertaken by two experienced operators&#46; These criteria were correlated with the histopathological results and the sensitivity&#44; specificity&#44; and positive and negative predictive values &#40;PPV and NPV&#41; were calculated&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Both heterogenicity and absence of CHS had the highest sensitivity and NPV &#40;&#8805;90&#37;&#41; for predicting LN malignancy with acceptable inter-observer agreement &#40;92&#37; and 87&#37; respectively&#41;&#46; On real-time application&#44; the sensitivity and specificity of the score &#62;5 were 78&#37; and 86&#37; respectively&#59; only the absence of CHS&#44; round shape and size of LN were significantly associated with malignant LN&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A combination of different US criteria can be useful for the prediction of mediastinal LN malignancy and valid for real-time clinical application&#46;</p>"
      ]
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        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evaluar la utilidad de diferentes caracter&#237;sticas ecogr&#225;ficas para diferenciar los ganglios linf&#225;ticos &#40;GL&#41; benignos y malignos mediante ecograf&#237;a endobronquial &#40;EBUS&#41; y validar una puntuaci&#243;n para una aplicaci&#243;n cl&#237;nica <span class="elsevierStyleItalic">en tiempo real</span>&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se analizaron 208 GL mediast&#237;nicos procedentes de 141 pacientes&#46; Dos observadores evaluaron de manera independiente 6<span class="elsevierStyleHsp" style=""></span>criterios ecogr&#225;ficos diferentes &#40;eje menor &#8805;10<span class="elsevierStyleHsp" style=""></span>mm&#44; forma&#44; margen&#44; ecogenicidad y estructura hiliar central &#91;EHC&#93; y presencia de densidad hiperecog&#233;nica&#41;&#46; Se gener&#243; una puntuaci&#243;n simplificada en la que a la presencia de m&#225;rgenes bien definidos&#44; la forma redondeada y el eje menor &#8805;10<span class="elsevierStyleHsp" style=""></span>mm se les asignaba una puntuaci&#243;n de 1 y a la ecogenicidad heterog&#233;nea y la ausencia de EHC se les asignaba una puntuaci&#243;n de 1&#44;5&#46; La puntuaci&#243;n se evalu&#243; prospectivamente para la aplicaci&#243;n cl&#237;nica <span class="elsevierStyleItalic">en tiempo real</span> en 65 GL durante la EBUS llevada a cabo por 2 operadores experimentados en 39 pacientes&#46; Estos criterios se correlacionaron con los resultados histopatol&#243;gicos&#44; y se calcularon la sensibilidad&#44; la especificidad y los valores predictivos positivo &#40;VPP&#41; y negativo &#40;VPN&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La heterogeneidad y la ausencia de EHC fueron los par&#225;metros que mostraron la m&#225;xima sensibilidad y VPN &#40;&#8805;90&#37;&#41; en la predicci&#243;n de la malignidad de los GL&#44; con una coincidencia interobservadores aceptable &#40;92 y 87&#37;&#44; respectivamente&#41;&#46; En la aplicaci&#243;n <span class="elsevierStyleItalic">en tiempo real</span>&#44; la sensibilidad y la especificidad de la puntuaci&#243;n &#62;5 fueron del 78 y del 86&#37;&#44; respectivamente&#59; tan solo la ausencia de EHC&#44; la forma redondeada y el tama&#241;o de los GL mostraron una asociaci&#243;n significativa con la malignidad de estos&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La combinaci&#243;n de diferentes criterios ecogr&#225;ficos puede ser &#250;til en la predicci&#243;n de la malignidad de los GL mediast&#237;nicos y v&#225;lida para una aplicaci&#243;n cl&#237;nica <span class="elsevierStyleItalic">en tiempo real</span>&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Shafiek H&#44; Fiorentino F&#44; Peralta AD&#44; Serra E&#44; Esteban B&#44; Martinez R&#44; et al&#46; Predicci&#243;n en tiempo real de la malignidad de ganglios linf&#225;ticos mediast&#237;nicos mediante ecograf&#237;a endobronquial&#46; Arch Bronconeumol&#46; 2014&#59;50&#58;228&#8211;234&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Series of EBUS images of the mediastinal lymph node showing the different criteria&#58; &#40;A&#41; heterogeneous echogenicity with a distinct margin in a reactive lymph node&#46; &#40;B&#41; Homogeneous echogenicity with an indistinct margin in a reactive lymph node&#46; &#40;C&#41; Heterogeneous echogenicity with a distinct margin in adenocarcinoma&#46; &#40;D&#41; Hyperechogenic density in the interior of a lymph node &#40;arrow&#41; in small cell carcinoma&#46; The lymph node images &#40;A&#8211;D&#41; show the absence of central hilar structure&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Series of EBUS images of the mediastinal lymph node showing the different criteria &#40;<span class="elsevierStyleItalic">continued</span>&#41;&#46; &#40;A&#41; Presence of central hilar structure &#40;arrow&#41; in reactive lymph node&#46; &#40;B and C&#41; Presence of central hilar structure with blood vessel &#40;arrow&#41; in another reactive lymph node&#59; demonstration in Doppler mode in &#40;C&#41;&#46; &#40;D&#41; Indistinct margin with heterogeneous echogenicity in extrathoracic metastasis with the absence of central hilar structure&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">ROC curve of the score for the prediction of malignant lymph node infiltration&#46; &#40;A&#41; ROC curve for the retrospective study showing different sensitivities and specificities of the combined positive criteria &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;738&#59; 95&#37; CI&#58; 0&#46;673&#8211;0&#46;796&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; &#40;B&#41; ROC curve for the prospective study &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;852&#59; 95&#37; CI&#58; 0&#46;743&#8211;0&#46;928&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">L&#44; left&#59; LN&#44; lymph node&#59; R&#44; right&#59; SD&#44; standard deviation&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleBold">Age &#40;years&#41; &#91;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">SD&#93;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">63&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Males&#58;</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span><span class="elsevierStyleBold">&#40;&#37;&#41;&#47;females&#58;</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span><span class="elsevierStyleBold">&#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">117 &#40;83&#41;&#47;24 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Affected LN &#40;</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">208&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">4R</span>&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">4L</span>&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">2R</span>&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">6</span>&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Stations 10&#8211;12</span>&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;16&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:1.0px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Pathology diagnosis&#58; malignant cases</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Primary lung cancer</span></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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Adenocarcinoma&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;22&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Squamous cell carcinoma&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;12&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Small cell lung cancer&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;6&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Undifferentiated non-small cell lung cancer&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;6&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Small cell carcinoma&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Other</span></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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Extrathoracic metastasis&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;5&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Lymphoma&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab509290.png"
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        ]
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">CHS&#44; central hilar structure&#59; CI&#44; confidence interval&#59; IRA&#44; interrater agreement&#59; LN&#44; lymph node&#59; ND&#44; not determined&#59; NPV&#44; negative predictive value&#59; PVV&#44; positive predictive value&#46;</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"><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">Sonographic criteria&nbsp;\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">Sensitivity &#40;95&#37; CI&#41;&nbsp;\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">Specificity &#40;95&#37; CI&#41;&nbsp;\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">PPV &#40;95&#37; CI&#41;&nbsp;\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">NPV &#40;95&#37; CI&#41;&nbsp;\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">IRA&nbsp;\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Round shape&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91&#46;3&#37; &#40;83&#46;8&#8211;95&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;2&#37; &#40;18&#46;3&#8211;36&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;6&#37; &#40;47&#46;8&#8211;63&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#37; &#40;57&#46;5&#8211;87&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Short axis &#8805;1<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#46;5&#37; &#40;81&#46;6&#8211;94&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#37; &#40;26&#46;9&#8211;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&#46;1&#37; &#40;60&#46;5&#8211;76&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;5&#37; &#40;55&#46;9&#8211;84&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heterogeneous echogenicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#37; &#40;94&#8211;99&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;5&#37; &#40;10&#46;2&#8211;25&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#46;7&#37; &#40;47&#46;4&#8211;62&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">94&#46;4&#37; &#40;70&#46;6&#8211;99&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hyperechogenic density in the interior of the LN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#37; &#40;13&#46;9&#8211;30&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37; &#40;68&#46;4&#8211;85&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#37; &#40;34&#8211;64&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#46;4&#37; &#40;41&#46;5&#8211;57&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Absence of any CHS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#37; &#40;94&#46;8&#8211;99&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;7&#37; &#40;4&#46;1&#8211;16&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#46;5&#37; &#40;45&#46;3&#8211;59&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#37; &#40;54&#46;1&#8211;99&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Distinct margin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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