Scientific Letter
Negative Endobronchial Ultrasound in Lung Cancer Staging
Ecobroncoscopia negativa en la estadificación del carcinoma broncogénico
José Antonio Gullón Blanco
, Manuel Ángel Villanueva Montes, Juan Rodríguez López, Andrés Sánchez Antuña
Corresponding author
Unidad de Gestión Clínica Neumología, Hospital Universitario San Agustín, Avilés, Asturias, Spain
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"pii" => "S1579212917303129" "issn" => "15792129" "doi" => "10.1016/j.arbr.2017.09.008" "estado" => "S300" "fechaPublicacion" => "2017-11-01" "aid" => "1589" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2017;53:644-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1243 "formatos" => array:3 [ "EPUB" => 147 "HTML" => 754 "PDF" => 342 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Richter Syndrome With Extensive Isolated Pleural Extranodal Involvement: The Importance of PET/CT Imaging" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "644" "paginaFinal" => "646" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de Richter con extensa afectación extranodal pleural aislada: importancia de la PET/TC" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 857 "Ancho" => 2195 "Tamanyo" => 142201 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) PET axial image of the chest revealing hypermetabolic circumferential thickening of the pleural surface of the right hemithorax. Note the increased thickening of the posterior pleural surface (arrows). (B) PET coronal image revealing hypermetabolic thickening of the pleural surface of the right hemithorax (short arrows). Note also the intense FDG uptake by the oblique fissure (long arrow). (C) PET–CT fusion axial image showing marked hypermetabolic thickening of the pleural surface of the right hemithorax at the level of the posterior costophrenic angle. On the basis of these images, this region was selected for biopsy.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Luis Gorospe Sarasúa, Ana Jaureguízar-Oriol, Carlos Almonacid-Sánchez, María Eugenia Rioja-Martín" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Luis" "apellidos" => "Gorospe Sarasúa" ] 1 => array:2 [ "nombre" => "Ana" "apellidos" => "Jaureguízar-Oriol" ] 2 => array:2 [ "nombre" => "Carlos" "apellidos" => "Almonacid-Sánchez" ] 3 => array:2 [ "nombre" => "María Eugenia" "apellidos" => "Rioja-Martín" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0300289617300704" "doi" => "10.1016/j.arbres.2017.03.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289617300704?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212917303129?idApp=UINPBA00003Z" "url" => "/15792129/0000005300000011/v2_201711201359/S1579212917303129/v2_201711201359/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Negative Endobronchial Ultrasound in Lung Cancer Staging" "tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "646" "paginaFinal" => "647" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "José Antonio Gullón Blanco, Manuel Ángel Villanueva Montes, Juan Rodríguez López, Andrés Sánchez Antuña" "autores" => array:4 [ 0 => array:4 [ "nombre" => "José Antonio" "apellidos" => "Gullón Blanco" "email" => array:1 [ 0 => "josegubl@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Manuel Ángel" "apellidos" => "Villanueva Montes" ] 2 => array:2 [ "nombre" => "Juan" "apellidos" => "Rodríguez López" ] 3 => array:2 [ "nombre" => "Andrés" "apellidos" => "Sánchez Antuña" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Gestión Clínica Neumología, Hospital Universitario San Agustín, Avilés, Asturias, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ecobroncoscopia negativa en la estadificación del carcinoma broncogénico" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Endobronchia ultrasound-guided transbronchial aspiration (EBUS-TBNA) is the primary method of non-invasive staging in non-small cell lung cancer (NSCLC), due to its low morbidity, low cost, and similar sensitivity to mediastinoscopy.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> However, in case of a negative EBUS-TBA, the need to obtain another sample by mediastinoscopy is controversial. The aim of this study was to determine the negative predictive value (NPV) of EBUS-TBNA in NSCLC lymph node staging.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A retrospective analysis was performed of data collected prospectively in a database that included all patients who underwent EBUS-TBNA for mediastinal lymph node staging and positron emission tomography-computed tomography (PET–CT). Two samples (if the pathologist was present in the examination room) or 3 samples (if the pathologist was absent) were obtained from lymph node stations measuring >5<span class="elsevierStyleHsp" style=""></span>mm in their smallest diameter or those measuring <5<span class="elsevierStyleHsp" style=""></span>mm with pathological uptake in PET–CT. The specimen was considered: <span class="elsevierStyleItalic">(1) representative</span> if more than 300 lymphocytes in total or more than 150 lymphocytes/field were observed on cytological examination; <span class="elsevierStyleItalic">(2) positive</span> if malignant cells were detected; and <span class="elsevierStyleItalic">(3) negative</span> in the absence of malignant cells and presence of a representative number of lymphocytes. The gold standard for demonstrating the presence or absence of nodal infiltration was the histological analysis of the mediastinal lymph node specimens obtained by thoracotomy or VATS. The following formula was used to calculate the NPV: true negatives (TN)/true negatives+false negatives (FN). TN was defined as negative EBUS-TBA confirmed by thoracotomy or VATS, and FN as negative EBUS-TNA with malignant cells observed on thoracotomy or VATS.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A total of 97 patients with NSCLC were identified, of whom 23 had undergone surgical resection with mediastinal lymph node dissection, and this group formed the final study cohort. Fifteen were men, and mean age was 65.49±9.8 years. Samples from 35 enlarged lymph nodes were obtained by EBUS-TBNA and thoracotomy/VATS, and results were concordant in 32: 11/12 in E7, 9/10 in 4R, 8/9 in 4L, 3/3 in 10R and 1/1 in 11L. Three false negatives were obtained, as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The prevalence of mediastinal lymph node infiltration with negative EBUS-TBNA was 8.6%, with a NPV per lymph node of 91.4%. In total, 30 lymphadenopathies showed pathological uptake on PET–CT: 24 N2 (cN2) and 6 N3 (cN3), with a prevalence and NPV of 12% and 87.5%, and 0% and 100%, respectively.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Recent clinical guidelines<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,2</span></a> recommend mediastinoscopy after a negative EBUS when the mediastinum is abnormal, defined as the presence of enlarged lymph nodes with pathological uptake on PET–CT, according to the conclusions of a Bayesian analysis which determined that the post-test probability of malignancy in this group of patients would be high, at around 20%.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> This estimate was made by taking into account the results of the ASTER study,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> a trial comparing EBUS-TBNA with EBUS-TBNA plus mediastinoscopy, randomized at a ratio of 1:1, which showed that the combination of both techniques was more sensitive than each one separately.</p><p id="par0025" class="elsevierStylePara elsevierViewall">However, this conclusion is rather controversial. In our series, in patients with a moderate to high risk of N2-N3, the NPV of EBUS-TBNA is high, in line with findings from various studies in which it ranged between 89% and 99%.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">5–9</span></a> According with these results, the possibility has been raised that in resectable NSCLC, a negative EBUS-TBNA would not need further confirmation by mediastinoscopy, as suggested by recent guidelines from the Spanish Society of Pulmonology and Thoracic Surgery.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> This recommendation is further strengthened by evidence that mediastinoscopy is not superior to EBUS-TBNA in nodal staging, and indeed its sensitivity is similar and sometimes lower.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">11,12</span></a> This was also shown in the ASTER study,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> which reported that to improve sensitivity, 11 mediastinoscopies would have to be performed to obtain 1 positive case. Therefore, as the authors themselves admit, confirming all cases with negative EBUS-TBNA by mediastinoscopy might not be necessary.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Nevertheless, it would be advisable to try to identify any features that could be associated with a greater likelihood of “unexpected” nodal involvement. In this respect, our study revealed that our 3 false negatives had the common factor of a centrally located tumor, predominantly in the upper lobes. This finding has already been recognized as a predictor of malignancy in patients with negative EBUS-TBNA: Ong et al.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> showed that the presence of nodal metastases in patients with a normal mediastinum according to imaging techniques, of which 37% were detected by EBUS-TBNA, correlated significantly with central tumors, and of these, 67% were located in the upper lobes, a finding similar to that obtained in previous prospective studies.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> Similarly, Talebian Yazdi et al.,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> in a large series, found that central tumor location, along with enhanced uptake on PET, were factors predictive of false negatives in subjects with negative EBUS-TBNA.</p><p id="par0035" class="elsevierStylePara elsevierViewall">This study has the limitations typical of a retrospective design and a small sample size, so definitive conclusions cannot be reached in certain aspects, such as the possible influence of PET uptake on EBUS-TBNA false negatives. However, the limitations of imaging studies in this regard are well known,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> and if they are taken into account, we believe that our results could be of use for identifying patients in whom it may be appropriate to perform mediastinoscopy after lymph node staging by EBUS-TBNA. We were also unable to calculate the sensitivity or the positive predictive value of the technique, because positive EBUS-TBNA results are not generally confirmed by surgery.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We conclude that in patients with potentially resectable non-small cell lung cancer, a negative preoperative EBUS-TBNA might not require confirmation by mediastinoscopy in most cases, perhaps with the exception of centrally located tumors.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Gullón Blanco JA, Villanueva Montes MÁ, Rodríguez López J, Sánchez Antuña A. Ecobroncoscopia negativa en la estadificación del carcinoma broncogénico. Arch Bronconeumol. 2017;53:646–647.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">LN: lymph node; LUL: left upper lobe; RUL: right upper lobe.</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">Primary Tumor \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">LN With PET–CT Uptake \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">LN Diameter (mm) \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">LNs Analyzed \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">Malignancy on Surgery \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">LUL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4L \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">RUL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E7, 11L, 10R \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11, 8, 5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E7, 11L, 10R \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E7 \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">RUL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4R \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4R \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1592635.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">EBUS-TNA False Negatives.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ten years of linear endobronchial ultrasound: evidence of efficacy, safety and cost-effectiveness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. 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| Year/Month | Html | Total | |
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| 2024 November | 4 | 4 | 8 |
| 2024 October | 79 | 16 | 95 |
| 2024 September | 71 | 16 | 87 |
| 2024 August | 87 | 33 | 120 |
| 2024 July | 71 | 32 | 103 |
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| 2024 May | 115 | 29 | 144 |
| 2024 April | 55 | 26 | 81 |
| 2024 March | 44 | 12 | 56 |
| 2024 February | 51 | 19 | 70 |
| 2023 March | 13 | 4 | 17 |
| 2023 February | 49 | 22 | 71 |
| 2023 January | 41 | 25 | 66 |
| 2022 December | 64 | 29 | 93 |
| 2022 November | 71 | 26 | 97 |
| 2022 October | 68 | 31 | 99 |
| 2022 September | 59 | 39 | 98 |
| 2022 August | 54 | 48 | 102 |
| 2022 July | 58 | 34 | 92 |
| 2022 June | 67 | 41 | 108 |
| 2022 May | 59 | 35 | 94 |
| 2022 April | 106 | 32 | 138 |
| 2022 March | 93 | 47 | 140 |
| 2022 February | 102 | 20 | 122 |
| 2022 January | 89 | 34 | 123 |
| 2021 December | 46 | 44 | 90 |
| 2021 November | 77 | 54 | 131 |
| 2021 October | 64 | 45 | 109 |
| 2021 September | 41 | 50 | 91 |
| 2021 August | 40 | 39 | 79 |
| 2021 July | 37 | 36 | 73 |
| 2021 June | 66 | 46 | 112 |
| 2021 May | 90 | 39 | 129 |
| 2021 April | 134 | 85 | 219 |
| 2021 March | 85 | 29 | 114 |
| 2021 February | 40 | 26 | 66 |
| 2021 January | 38 | 16 | 54 |
| 2020 December | 40 | 16 | 56 |
| 2020 November | 34 | 12 | 46 |
| 2020 October | 40 | 18 | 58 |
| 2020 September | 28 | 12 | 40 |
| 2020 August | 48 | 13 | 61 |
| 2020 July | 36 | 22 | 58 |
| 2020 June | 26 | 11 | 37 |
| 2020 May | 32 | 7 | 39 |
| 2020 April | 31 | 22 | 53 |
| 2020 March | 38 | 10 | 48 |
| 2020 February | 35 | 15 | 50 |
| 2020 January | 30 | 15 | 45 |
| 2019 December | 54 | 19 | 73 |
| 2019 November | 42 | 30 | 72 |
| 2019 October | 38 | 10 | 48 |
| 2019 September | 32 | 12 | 44 |
| 2019 August | 29 | 16 | 45 |
| 2019 July | 29 | 13 | 42 |
| 2019 June | 36 | 8 | 44 |
| 2019 May | 54 | 21 | 75 |
| 2019 April | 46 | 46 | 92 |
| 2019 March | 39 | 26 | 65 |
| 2019 February | 33 | 17 | 50 |
| 2019 January | 27 | 18 | 45 |
| 2018 December | 32 | 16 | 48 |
| 2018 November | 91 | 26 | 117 |
| 2018 October | 101 | 26 | 127 |
| 2018 September | 36 | 9 | 45 |
| 2018 May | 17 | 0 | 17 |
| 2018 April | 68 | 15 | 83 |
| 2018 March | 36 | 5 | 41 |
| 2018 February | 29 | 7 | 36 |
| 2018 January | 4 | 0 | 4 |
| 2017 November | 1 | 0 | 1 |
| 2017 October | 0 | 1 | 1 |
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