Thoracic ultrasound combined with low-dose computed tomography may represent useful screening strategy in highly exposed population in the industrial city of Taranto (Italy).

Objectives: We validated a screening protocol in which thoracic ultrasound (TUS) acts as a first-line complementary imaging technique in selecting patients which may deserve a second-line low-dose high resolution computed tomography (HRCT) scan among a population of asymptomatic high-risk subjects for interstitial lung abnormalities (ILA) and lung cancer. Due to heavy environmental pollution burden, the district Tamburi of Taranto has been chosen as "case study" for this purpose. Methods: From July 2018 to October 2020, 677 patients aged between 45 and 65 year and who had been living in the Tamburi district of Taranto for at least 10 years were included in the study. After demographic, clinical and risk factor exposition data were collected, each participant underwent a complete TUS examination. These subjects were then asked to know if they agreed to perform a second-level examination by low-dose HRCT scan. Results: On a total of 167 subjects (24.7%) who agreed to undergo a second-level HRCT, 85 patients (50.9%) actually showed pleuro-pulmonary abnormalities. Interstitial abnormalities were detected in a total of 36 patients on HRCT scan. In particular, 34 participants presented subpleural ILAs, that were classified in the fibrotic subtype in 7 cases. The remaining 2 patients showed non-subpleural interstitial abnormalities. Subpleural nodules were observed in 46 patients. TUS showed an overall diagnostic accuracy of 88.6% in detecting pleuro-pulmonary abnormalities in comparison with HRCT scan, with a sensitivity of 95.3%, a specificity of 81.7%, a positive predictive value of 84.4% and a negative predictive value of 94.4%. The matched evaluation of specific pulmonary abnormalities on HRTC scan (i.e., interstitial abnormalities or pulmonary nodules) with determinate sonographic findings revealed a reduction in both TUS sensibility and specificity. Focusing TUS evaluation on the assessment of interstitial abnormalities, a thickened pleural line showed a sensitivity of 63.9% and a specificity of 69.5%, hypoechoic striae showed a sensitivity of 38.9% and a specificity of 90.1% and subpleural nodules showed a sensitivity of 58.3% and a specificity of 77.1%. Regarding to the assessment of subpleural nodules, TUS showed a sensitivity of 60.9% and a specificity of 81.0%. However, the combined employment of TUS examination and HRCT scans allowed to identify 34 patients with early subpleural ILA and to detect three suspicious pulmonary nodules (of which two were intraparenchymal and one was a large subpleural mass), which revealed to be lung cancers on further investigations. Conclusion: A first-line TUS examination might aid the identification of subjects highly exposed to environmental pollution, who could benefit of a second-line low-dose HRCT scan to find early interstitial lung diseases as well as lung cancer. Protocol registration code: PLEURO-SCREENING-V1.0_15 Feb, 17.

Effectiveness and Safety of Real-Time Transthoracic Ultrasound-Guided Thoracentesis.

PURPOSE: The purpose of the present study was to specifically evaluate the effectiveness and safety of real-time ultrasound-guided thoracentesis in a case series of pleural effusion. PATIENTS AND METHODS: An observational prospective study was conducted. From February 2018 to December 2019, a total of 361 consecutive real-time transthoracic ultrasound (TUS)-guided thoracentesis were performed in the Unit of Diagnostic and Interventional Ultrasound of the Research Hospital "Fondazione Casa Sollievo della Sofferenza" of San Giovanni Rotondo, Foggia, Italy. The primary indication for thoracentesis was therapeutic in all the cases (i.e., evacuation of persistent small/moderate pleural effusions to avoid super-infection; drainage of symptomatic moderate/massive effusions). For completeness, further diagnostic investigations (including chemical, microbiological, and cytological analysis) were conducted. All the procedures were performed by two internists with more than 30 years of experience in interventional ultrasound using a multifrequency convex probe (3-8 MHz). For pleural effusions with a depth of 2-3 cm measured at the level of the costo-phrenic sinus was employed a dedicated holed convex-array probe (5 MHz). RESULTS: In all the cases, the attempts at thoracentesis were successful, allowing the achievement of the therapeutic purpose of the procedure (i.e., the complete drying of the pleural space or the withdrawal of fluid till a "safe" quantity [a mean of 1.5 L, max 2 L] producing relief from symptoms) regardless of the initial extent of the pleural effusion. There were only 3 cases of pneumothorax, for a prevalence rate of complications in this population of 0.83%. No statistical difference was recorded in the rate of pneumothorax according to the initial amount of pleural fluid in the effusion (p = 0.12). All the pleural effusions classified as transudates showed an anechoic TUS appearance. Only the exudative effusions showed a complex nonseptated or a hyperechoic TUS appearance. However, an anechoic TUS pattern was not unequivocally associated with transudates. Some chronic transudates have been classified as exudates by Light's criteria, showing also a complex nonseptated TUS appearance. The cytological examination of the drained fluid allowed the detection of neoplastic cells in 15.89% cases. On the other hand, the microbiological examination of effusions yielded negative results in all the cases. CONCLUSIONS: Real-time TUS-guided thoracentesis is a therapeutically effective and safe procedure, despite the diagnostic yield of the cytological or microbiological examinations on the collected liquid being very low. Future blinded randomized studies are required to definitely clarify the actual benefit of the real-time TUS-guided procedure over percussion-guided and other ultrasound-based procedures.

Which are the limiting factors in lung tissue sampling and diagnostic accuracy for a new Interventional Pulmonology Unit? From expert consensus-based evidence to results of a new-born Unit.

BACKGROUND: There is a gap of knowledge about the factors that may determine the quality and the accuracy of diagnostic bronchoscopic procedures when setting up a new Interventional Pulmonology Unit. As little evidence-based medicine is available on this matter, an online consensus opinion of experts was gathered and compared with real-life data coming from a new Interventional Pulmonology (IP) Unit. METHODS: A survey was emailed to the heads of all Italian IP Units to investigate the factors influencing the success of the diagnostic yield of a new IP Unit. The survey consisted of 24 items grouped by topic; the level of agreement ranged from 1 (no influence) to 7 (strong influence). After responses were collected, we submitted the data on the accuracy of the endoscopic procedures performed during the first two years of our new IP Unit to the attention of the participants for a second round of survey; the level of consistency between the first and second round of responses was assessed. RESULTS: After having been shown the results of the first two years of activity of our Unit, in the second round of the survey the responders indicated the personal skills of the Interventional Pulmonologist, the availability of echoendoscopic technology and the expertise in evaluating cytological samples as the factors able to positively influence the performance of a newly established IP Unit. Neither the role of dedicated nursing assistance, the availability of a rapid on-site evaluation, nor the presence of anesthesiology assistance were considered to be limiting factors for the final accuracy results. CONCLUSIONS: A consensus of opinion of a group of expert interventional pulmonologists highlighted the factors that may be responsible for the diagnostic success of a newly established Italian IP Unit. These factors are mainly three: personal skills of the interventional pulmonologist, the availability of echoendoscopic technology, and the expertise in reading cytological samples.

Pharmacokinetic drug evaluation of osimertinib for the treatment of non-small cell lung cancer.

INTRODUCTION: First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial activity of an average 9-13 months, disease progression has been reported in the majority of patients. In about 50% of cases the progression is due to the onset of the T790M mutation in exon 20 of the EGFR gene. Third-generation EGFR-TKIs targeting this mutation were investigated, with osimertinib the only reaching clinical practice. Areas covered: A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question addressing osimertinib, was undertaken. Expert opinion: Osimertinib is the standard-of-care for EGFR-mutated patients progressing to first-line EGFR-TKIs due to the acquired EGFR T790M mutation. Results from the head-to-head first-line trial comparing osimertinib versus gefitinib or erlotinib in activating EGFR mutations might change the front-line approach. Osimertinib in combination regimens, such as immunotherapy, and in adjuvant setting are ongoing. Thus, the strategic approach for the management of EGFR-mutated NSCLC patients will change further in the next few years.