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A tissue diagnosis is often required to confirm malignity, with endobronchial biopsies being associated with a lower pneumothorax rate than percutaneous approaches. Endoscopic diagnosis of peripheral small size lung nodules is however often challenging using traditional bronchoscopy and endobronchial ultrasound alone. New virtual bronchoscopic navigation techniques such as electromagnetic navigational bronchoscopy (ENB) have developed to improve peripheral navigation, with diagnostic yield however remaining in the 30\u201350% range for small lesions. Recent studies have shown the benefits of combining Cone beam computed tomography (CBCT) with ENB to improve diagnostic yield to up to 83%. The use of ENB however remains limited by disposable cost, bronchus sign dependency and inaccuracies due to CT to body divergence.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>This case report highlights the feasibility and usefulness of CBCT-guided bronchoscopy for the sampling of lung nodules difficult to reach through traditional bronchoscopy because of nodule size and peripheral position. Procedure was scheduled in a mobile robotic hybrid operating room with patient under general anaesthesia. CBCT acquisition was performed to localize the target lesion and plan the best path to reach it into bronchial tree. A dedicated software was used to segment the lesion and the bronchial path which 3D outlines were automatically fused in real time on the fluoroscopic images to augment live guidance. Navigation to the lesion was guided with bronchoscopy and augmented fluoroscopy alone. Before the sampling, CBCT imaging was repeated to confirm the proper position of the instrument into the lesion. Four transbronchial needle aspirations (TBNA) were performed and the tissue analysis showed a primary lung adenocarcinoma.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>CBCT and augmented fluoroscopy technique is a safe and effective and has potential to improve early stage peripheral lesions endobronchial diagnostic yield without ENB. Additional studies are warranted to confirm its safety, efficacy and technical benefits, both for diagnosis of oncological and non-oncological disease and for endobronchial treatment of inoperable patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12890-021-01697-y","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T11:31:08Z","timestamp":1634729468000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cone beam CT augmented fluoroscopy allows safe and efficient diagnosis of a difficult lung nodule"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1046-4848","authenticated-orcid":false,"given":"Roberto","family":"Piro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Casalini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Taddei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Bertolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Iori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Facciolongo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"1697_CR1","unstructured":"World Health Organization. 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