Scientific Letter
Transbronchial Cryobiopsy in the First 51 Patients: Diagnostic Yield, Complication Rates and Survival After 8 Years
Criobiopsia transbronquial en los primeros 51 pacientes: rendimiento diagnóstico, tasa de complicaciones y supervivencia después de 8 años
Antolina Gómez Lópeza,
, Arschang Valipourb, Eduardo de Miguel Pocha, Ricardo García Lujána, Roberto del Pozo Rivasc, Raquel Pérez Rojoa, Ana Belén Enguita Valsd, Sergio Alonso Charterinae, Ignacio de Granda Orivea, Carlos José Álvarez Martíneza, Virginia Pérez Gonzáleza, Pablo Gámez Garcíaf, Manuel Cortés Guerrerog, Victoria Villena Garridoa
Corresponding author
a Pneumology Service, 12 de Octubre University Hospital, Madrid, Spain
b Karl-Landsteiner-Institute for Lung Research, Klinik Floridsdorf, Vienna, Austria
c Pneumology Service, Juan Ramón Jiménez University Hospital, Huelva, Spain
d Pathology Department, 12 de Octubre University Hospital, Madrid, Spain
e Radiodiagnostic Service, 12 de Octubre University Hospital, Madrid, Spain
f Thoracic Surgery Service, 12 de Octubre University Hospital, Madrid, Spain
g Anesthesiology Service, 12 de Octubre University Hospital, Madrid, Spain
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"etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 12 => array:3 [ "nombre" => "Manuel" "apellidos" => "Cortés Guerrero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 13 => array:3 [ "nombre" => "Victoria" "apellidos" => "Villena Garrido" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Pneumology Service, 12 de Octubre University Hospital, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Karl-Landsteiner-Institute for Lung Research, Klinik Floridsdorf, Vienna, Austria" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Pneumology Service, Juan Ramón Jiménez University Hospital, Huelva, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Pathology Department, 12 de Octubre University Hospital, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Radiodiagnostic Service, 12 de Octubre University Hospital, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Thoracic Surgery Service, 12 de Octubre University Hospital, Madrid, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Anesthesiology Service, 12 de Octubre University Hospital, Madrid, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Criobiopsia transbronquial en los primeros 51 pacientes: rendimiento diagnóstico, tasa de complicaciones y supervivencia después de 8 años" ] ] "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" => 1004 "Ancho" => 2508 "Tamanyo" => 99969 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Fluoroscopy with rigid bronchoscopy, inserted cryoprobe through videobronchoscopy and less than 1<span class="elsevierStyleHsp" style=""></span>cm from the pleural surface. (B) Kaplan–Meier survival curve in diagnosis of UIP after TBCx.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In September 2004, Alexander Babiak, an interventional pulmonologist from Ulm (Germany), used transbronchial cryobiopsy (TBCx) technique for the first time in 7 patients with interstitial lung disease (ILD).<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">1</span></a> Since then, multiple studies have been reported with varying results on diagnostic yield and complication rates associated with this technique.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In this descriptive retrospective study, we will provide information about patient characteristics, diagnostic yield and complication rates of all TBCx performed in the first 51 patients, between April 2014 and August 2016, at the 12 de Octubre University Hospital, for the diagnosis of ILD or suspected rejection post lung transplantation (LT), approved by the Ethics Committee under number 13/202.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Patients were required to have a chest computed tomography (CT) within a month prior to the procedure, in those patients with typical features of usual interstitial pneumonia (UIP) on CT, TBCx was not performed. Exclusion criteria for TBCx were: bleeding diathesis, thrombocytopenia (<50<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L) and severe respiratory functional impairment.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a> After informed consent regarding diagnostic yield and risks of TBCx and an evaluation of the anesthesiological risk, patients scheduled for TBCx were admitted to the department the same day of TBCx and thereafter discharged in <24<span class="elsevierStyleHsp" style=""></span>h if they presented with clinical and radiological stability.</p><p id="par0020" class="elsevierStylePara elsevierViewall">All were performed using rigid bronchoscopy (RB) by “Effer Dumon”. Following intubation, an Olympus balloon was placed in the selected bronchus (when the target was located in the upper lobes, placement was achieved with the help of a biopsy forceps). Then a cryoprobe (1.9 or 2.4<span class="elsevierStyleHsp" style=""></span>mm size, depending on the preference of the endoscopist, Erbokryo® CA, 10448-000 model ERBE Elektromedizin, Tübingen, Germany) was introduced via the working channel of the therapeutic videobronchoscope (VBC) (Olympus® BF-190) and under fluoroscopic was positioned at a distance of 10–20<span class="elsevierStyleHsp" style=""></span>mm from the pleura (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A), then it was cooled for approximately 3–5<span class="elsevierStyleHsp" style=""></span>s, retracted together en bloc and the balloon was inflated. Biopsies was taken from one or more of the most affected segments. It was repeated to obtain at least 3 adequate biopsies. All biopsies were evaluated by a pathologist specialized in Pulmonology.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Mild bleeding was considered if it resolved with simple aspiration, moderate if it was necessary to apply cold saline and/or chemical vasoconstrictor, or severe if selective intubation was necessary and/or admission to intensive care.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Patients with non-definite patterns or inconclusive histological results were discussed in a multidisciplinary meeting, in order to obtain consensus on diagnostic.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The statistical analysis was performed with the program SPSS v. 20.0 for Mac. Statistical significance a <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05. Patient survival was drawn by the Kaplan–Meier method and different groups were compared with the Log Rank test.</p><p id="par0040" class="elsevierStylePara elsevierViewall">A total of 51 patients (26 men (51%)), mean age 63 years (range 56–71) underwent TBCx at our institution, with median diffusing capacity for lung carbon monoxide 66% (51–76). The overall diagnostic yield was of 78.4% (40 patients). The most frequent pathology was UIP (12, 30% of total) followed by organizing pneumonia (OP) 15%, and sarcoidosis 8%. In 3 patients a repeat TBCx was performed, due to lack of conclusive diagnosis following the first sampling, being diagnostic after second one. Furthermore, TBCx were performed in 5 patients with suspected rejection post LT, rejection was confirmed in 2 patients (33%).</p><p id="par0045" class="elsevierStylePara elsevierViewall">Of the 11 non-diagnostic samples; 4 biopsy specimens demonstrated exclusively bronchial wall histology (in 1 of them a second TBCx was performed with a diagnosis of UIP) and 7 samples showed parenchyma without pathology. Two of these underwent surgical biopsy; one turned out to be UIP and the other sample revealed emphysema. The other 8 patients were followed up clinically and radiologically to ascertain a final diagnosis.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Four (8%) developed a pneumothorax, all of them required chest drainage. One of these patients had an acute exacerbation with subsequent clinical worsening and respiratory failure, resulting in death at 13 days following TBCx (showed a histological UIP pattern, that was associated with a Sjögren's syndrome).</p><p id="par0055" class="elsevierStylePara elsevierViewall">Mild bleeding occurred in 7 patients (14%), moderate in 3 patients (6%) and no severe.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The follow up of these 51 patients evaluated after 8 years from the beginning of using TBCx: 30 patients (59%) were alive as of June 2022, and 21 patients died. Median overall survival was 78 months (range 44–88 months). Overall survival of those with a histological UIP pattern based on TBCx sampling was 36% at 90 months, with worse prognosis compared to the 55% for those without UIP histology (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B).</p><p id="par0065" class="elsevierStylePara elsevierViewall">The most recent clinical practice guidelines on the diagnosis of idiopathic pulmonary fibrosis (IPF) refer to the use of TBCx and the challenges of obtaining appropriate material for the histopathological criteria for UIP. The limitations are particularly due to the subpleural predominance of pathologic changes and the potential for sampling errors resulting in less confident exclusion of features that may suggest an alternative diagnosis, compared with surgical lung biopsy (SLB).<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In fact, TBCx is more likely to demostrate a probable UIP pattern than a definite UIP pattern given the limited sampling of subpleural lung parenchyma in most cases.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">4</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Comparing diagnostic yields between major studies: MULTICRIO compared between classic transbronchial biopsies and TBCx in 124 subjects and according to histopathology results the diagnostic yield was higher for TBCx (55%) vs 19% (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001),<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a> other with 77 patients randomized to TBCx or forceps biopsy, were statistically significant differences: 74% for TBCx vs 34%,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> 69 patients: 76%<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> and 297 patients: 86%.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">8</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Mild to moderate bleeding is the most frequent complication, with reported rates as high as 78%.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">2,9</span></a> Time greater than 4<span class="elsevierStyleHsp" style=""></span>s with a larger size cryoprobe was considered as a risk factor according to a recent report.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> Pneumothorax rates vary between 0% and 28%<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">7,11–13</span></a> risk factors are the histological pattern of UIP, reticulation on CT and/or biopsies close to the pleura.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">While TBCx has yet not been established as the gold standard, cost and complications are lower than SLB, in the presence of a high concordance of the diagnostic utility.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">4</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Authors’ contributions</span><p id="par0090" class="elsevierStylePara elsevierViewall">All authors have made substantial contributions.</p><p id="par0095" class="elsevierStylePara elsevierViewall">All authors had worked to make possible this article which had supported very important aspects from the suspect of ILD or LT rejection to final diagnosis and treatment.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Informed consent</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors confirm that the patient's written consent has been obtained.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that they have not received any fees or funding for the development of the article.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors declare that they have no known competing financial interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Authors’ contributions" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Informed consent" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Funding" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflicts of interest" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1004 "Ancho" => 2508 "Tamanyo" => 99969 ] ] 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(B) Kaplan–Meier survival curve in diagnosis of UIP after TBCx.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:13 [ 0 => array:3 [ "identificador" => "bib0070" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transbronchial cryobiopsy as a new diagnostic method – a feasibility study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Babiak" 1 => "C. Schumann" 2 => "J. Hetzel" 3 => "M. Hetzel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eur. Respir. J." "fecha" => "2004" "volumen" => "48" "numero" => "Suppl." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 13 | 9 | 22 |
| 2024 September | 41 | 11 | 52 |
| 2024 August | 35 | 13 | 48 |
| 2024 July | 22 | 13 | 35 |
| 2024 June | 27 | 9 | 36 |
| 2024 May | 39 | 15 | 54 |
| 2024 April | 38 | 1 | 39 |
| 2024 March | 28 | 7 | 35 |
| 2024 February | 19 | 10 | 29 |
| 2024 January | 23 | 10 | 33 |
| 2023 December | 22 | 5 | 27 |
| 2023 November | 27 | 8 | 35 |
| 2023 October | 41 | 9 | 50 |
| 2023 September | 33 | 17 | 50 |
| 2023 August | 36 | 9 | 45 |
| 2023 July | 74 | 17 | 91 |
| 2023 June | 129 | 28 | 157 |
| 2023 May | 23 | 11 | 34 |
| 2023 April | 125 | 39 | 164 |
| 2023 March | 1 | 389 | 390 |
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