Daniele Magnini

Role of ultrasound-guided transbronchial biopsy in the diagnosis of peripheral pulmonary lesions.

INTRODUCTION Endobronchial ultrasound (EBUS) can be used as an alternative to fluoroscopy to visualize a peripheral pulmonary lesion (PPL) and to provide an image guidance for transbronchial biopsy (TBB). The aim of this study was to verify the accuracy of EBUS-guided TBB in the diagnosis of PPLs. METHODS All the patients with CT-scan evidence of PPL who underwent bronchoscopy with EBUS in the period between 2008 and 2011 were retrospectively evaluated. EBUS was performed using a radial-type miniature ultrasound probe. Once obtained an EBUS image of the PPL, we measured the distance of the PPL from the outer orifice of the working channel of the bronchoscope in order to perform TBB at PPL site. RESULTS A total of 662 patients were examined. The mean diameter of lesions was 36 ± 20 mm. PPLs were visualized in 494 patients (75%) and the TBB was performed in 479 patients. Thirty-two patients were lost in follow-up and data from 447 patients were analyzed. TBB results were 255 cancers and 192 non-malignant lesions. The final diagnosis reported was 359 cases of cancer and 88 of benign lesion. EBUS-guided TBB had a sensitivity of 71% for the diagnosis of cancer, a negative predictive value of 46% and an overall diagnostic accuracy of 77%. CONCLUSIONS These data obtained from a large series of patients and using an original method show that EBUS represents a valid support to bronchoscopy and that the EBUS-guided TBB has a high diagnostic yield in the diagnosis of PPLs.

Idiopathic Pulmonary Fibrosis: Molecular Endotypes of Fibrosis Stratifying Existing and Emerging Therapies

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown causes. Current diagnostic criteria are based on radiological, clinical, and histopathological features but, unfortunately, still many patients remain undiagnosed. Two currently approved therapies, pirfenidone and nintedanib, slow down disease progression but failed to block or revert it. On the other hand, many of the therapeutic agents tested in several clinical trials have not given satisfactory answers, probably due to the pathological heterogeneity of the disease. A growing number of studies show that IPF phenotype is the common clinical outcome of a variety of different pathophysiological mechanisms that identify disease subgroups characterised by specific genetic and molecular biomarkers (endotypes). The precision medicine approach is identifying and analysing the complex system of genetic, molecular, environmental, and behavioural variables underlying the development of the disease and the response to therapy. These molecular pathways are potential targets for novel agents and useful diagnostic, prognostic, and theragnostic biomarkers. We outline the status of knowledge in this field by discussing the complex pathogenetic pathways underlying different disease subgroups and assessing a stratification approach to novel therapeutic agents based on these endotypes.

Influence of the Learning Effect on the Diagnostic Yield of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration of Mediastinal and Hilar Lymph Nodes

Background: The diagnostic yield of conventional transbronchial needle aspiration (TBNA) is characterized by a learning effect. The aim of this retrospective study was to verify whether a learning curve similarly affected the yield of endobronchial ultrasound-guided (EBUS)-TBNA. To this end, we evaluated the sensitivity and diagnostic accuracy of EBUS-TBNA during the first 3 years of activity. Methods: EBUS-TBNA was performed by 2 operators with no previous experience in this technique. Cytologic samples were obtained from mediastinal and hilar lymph nodes enlarged at a chest computed tomography scan and/or with increased fluorodeoxyglucose uptake at computed tomography/positron emission tomography scan in patients with suspected lung cancer. The cytologic diagnosis of EBUS-TBNA samples has been compared with the final diagnosis obtained from further diagnostic procedures, surgery, or clinical-radiologic follow-up. Results: From October 2012 to October 2015, we collected 408 EBUS-TBNA cytologic samples from 313 patients: 223 samples were positive for metastatic involvement and 185 were nonmetastatic. The latter included 137 true-negative and 48 false-negative results. The final diagnosis comprised 271 metastatic and 137 nonmetastatic lymph nodes. The overall sensitivity for cancer was 82% and diagnostic accuracy was 88%. Sensitivity and accuracy per year were as follows: first year, 78% and 82% in 90 nodal samples; second year, 83% and 89% in 144 nodal samples; third year, 85% and 91% in 174 nodal samples. Conclusions: EBUS-TBNA can be considered as a reliable tool even if performed by operators without previous experience in this procedure, and the diagnostic yield continues to increase progressively over a long time.

Usefulness of Conventional Transbronchial Needle Aspiration for Sampling of Mediastinal Lymph Nodes in Lung Cancer.

Background:Transbronchial needle aspiration (TBNA) is recognized as a valuable tool for the sampling of mediastinal lymph nodes. In this study, we report data about the diagnostic yield of conventional TBNA in the diagnosis and staging of lung cancer. Methods:All patients with suspected lung cancer who underwent bronchoscopy with conventional TBNA in the years 2008 to 2012 were evaluated. TBNA was performed on mediastinal lymph nodes enlarged at chest computed tomography scan and/or with increased fluorodeoxyglucose uptake on positron emission tomography/computed tomography scan. Cytologic results derived from TBNA have been compared, with the final diagnosis obtained with other more invasive procedures and/or with a clinical-radiologic follow-up of at least 12 months. Results:TBNA was performed on 375 patients. However, 19 patients were lost to follow-up, and data from 356 patients with a total 459 TBNA specimens were analyzed. TBNA was positive for metastatic involvement of lymph nodes in 172 of 282 patients with cancer, with a sensitivity of 61%. Sensitivity achieved 65% when we considered the total of 459 TBNA specimens. The overall diagnostic accuracy of TBNA was 69%. The nodal stations more frequently examined were 7 (subcarinal: 190 TBNAs), 4R (right lower paratracheal: 147 TBNAs), and 10R (right hilar: 76 TBNAs), with a sensitivity of 66%, 66%, and 67%, respectively. Conclusion:Conventional TBNA remains a useful method for the diagnosis and staging of lung cancer, with a good diagnostic yield in several nodal stations.

Ultrasonography of the Mediastinum: Techniques, Current Practice, and Future Directions

In the everyday practice of respiratory physicians, ultrasound techniques play a key role by enabling several diagnostic and interventional procedures. The application of ultrasound to endoscopic procedures allows both a visualization and a guided sampling of mediastinal and hilar lymph nodes. Endobronchial ultrasound can be combined with transbronchial needle aspiration, and, similarly, endoscopic ultrasound can be combined with fine-needle aspiration to sample virtually all mediastinal nodal stations from the airways and the esophagus. Endobronchial ultrasound–transbronchial needle aspiration and endoscopic ultrasound–fine needle aspiration showed a complementary diagnostic yield, and, recently, endoscopic ultrasound with bronchoscope was introduced in clinical practice to perform a transesophageal needle aspiration by using an ultrasound bronchoscope. This technique allows a single operator to perform both transbronchial and transesophageal needle sampling with the same instrument during a single bronchoscopic procedure. Mediastinal staging impacts the management of patients affected by lung cancer, and the most recent guidelines clearly state that endobronchial ultrasound and endoscopic ultrasound should be the initial tissue sampling procedure over surgical staging. In addition, endoscopic ultrasound techniques demonstrated an excellent yield in diagnosing lymphoma and benign diseases, for example, sarcoidosis. The aim of this review was to discuss the current role and future perspectives of endosonography techniques available for the evaluation of the mediastinum. Special emphasis was placed on equipment and technical aspects, the diagnostic role, and future directions of development.

The technique of endoscopic airway tumor treatment

More than half of primary lung cancers are not resectable at diagnosis and 40% of deaths may be secondary to loco-regional disease. Many of these patients suffer from symptoms related to airways obstruction. Indications for therapeutic endoscopic treatment are palliation of dyspnea and other obstructive symptoms in advanced cancerous lesions and cure of early lung cancer. Bronchoscopic management is also indicated for all those patients suffering from benign or minimally invasive neoplasm who are not suitable for surgery due to their clinical conditions. Clinicians should select cases, evaluating tumor features (size, location) and patient characteristics (age, lung function impairment) to choose the most appropriate endoscopic technique. Laser therapy, electrocautery, cryotherapy and stenting are well-described techniques for the palliation of symptoms due to airway involvement and local treatment of endobronchial lesions. Newer technologies, with an established role in clinical practice, are endobronchial ultrasound (EBUS), autofluorescence bronchoscopy (AFB), and narrow band imaging (NBI). Other techniques, such as endobronchial intra-tumoral chemotherapy (EITC), EBUS-guided-transbronchial needle injection or bronchoscopy-guided radiofrequency ablation (RFA), are in development for the use within the airways. These endobronchial interventions are important adjuncts in the multimodality management of lung cancer and should become standard considerations in the management of patients with advanced lung cancer, benign or otherwise not approachable central airway lesions. We aimed at revising several endobronchial treatment modalities that can augment standard antitumor therapies for advanced lung cancer, including rigid and flexible bronchoscopy, laser therapy, endobronchial prosthesis, and photodynamic therapy (PDT).