The "Polonium In Vivo" Study: Polonium-210 in Bronchial Lavages of Patients with Suspected Lung Cancer.

Few studies have reported on polonium-210, a decay breakdown product of radon-222 and lead-210, in human lungs and there has been no study in patients with suspected lung cancer. The main aim of this "Polonium in vivo" study was to evaluate polonium-210 radioactivity in bronchopulmonary systems of smoker, ex-smoker and never smoker patients with suspected lung cancer. Alpha-spectrometric analyses were performed on bronchial lavage (BL) fluids from two Italian hospitals in 2013-2016. Socio-demographic, smoking, occupational and spirometric characteristics, lung cancer confirmation and histologic type and radon-222 concentration in patients' homes were collected. Seventy BL samples from never (n = 13), former (n = 35) and current smokers (n = 22) were analyzed; polonium-210 was detected in all samples from current and former smokers and in 54% of samples from never smokers (p < 0.001; median values: 1.20, 1.43 and 0.40 mBq, respectively). Polonium-210 levels were significantly higher in COPD versus no COPD patients (median value: 3.60 vs. 0.97 mBq; p = 0.007); former and current smokers, without and with COPD, had significantly increased polonium-210 levels (p = 0.012); 96% of confirmed versus 69% of non-confirmed lung cancer patients recorded detectable polonium-210 levels (p = 0.018). A polonium-210 detectable activity was measured in BL samples from all current and former smokers. Polonium-210 in the lungs could be the result of lead-210 entrapment, which, with its half-life of 22 years, could provide a continuous emission of alpha radioactivity, even many years after quitting, thus proposing a possible explanation for the onset of lung cancer, particularly in former smokers.

Competence and training in interventional pulmonology.

Interventional pulmonology (IP) is experiencing a rapid evolution of new technologies. There is a need to develop structured training programs, organized in high volume expert centers in order to improve trainee education, and including the development of validated metrics for their competency assessment. Concerning teaching methods, a gradual progression from theory to practice, using new teaching techniques, including live sessions and low and high-fidelity simulation, flipped classroom models and problem-based learning (PBL) exercises would provide a training setting more suitable for our current need to improve skills and update professionals. Training programs should be learner-centered and competence-oriented, as well as being based on a spiral-shaped approach in which the same subject is addressed many times, from new and different perspectives of knowledge, ability, behavior and attitude, until the trainee has demonstrated a high degree of skill and professionalism. Furthermore there is a need to standardize the training programs as guide for physicians wishing to undertake a gradual and voluntary improvement of their own competencies, and assist those planning and organizing training programs in IP. The article includes a general part on core curriculum contents, innovative training methods and simulation, and introduces the following articles on the skills that the Interventional Pulmonologist must master in order to perform the different procedures. This monography should be considered a starting point that will evolve over time and results in better training for practitioners and better care for our patients. The task of establishing a trainee's competence to practice independently as an Interventional Pulmonologist remains the responsibility of the IP fellowship program director and faculty, who validate logbooks and assess competence for each procedure. These standards need to be reviewed and approved by national and International Scientific Societies and Healthcare Institutions with the aim to improve, disseminate and incorporate them in healthcare programs.

Randomized Trial of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration With and Without Rapid On-site Evaluation for Lung Cancer Genotyping.

BACKGROUND: Experts and scientific society guidelines recommend that rapid on-site evaluation (ROSE) be used with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to optimize lung cancer genotyping, but no comparative trial has been carried out to confirm and quantify its usefulness. METHODS: To assess the influence of ROSE on the yield of EBUS-TBNA for a multigene molecular analysis of lung cancer samples, consecutive patients with suspected or known advanced lung cancer were randomized to undergo EBUS-TBNA without ROSE (EBUS arm) or with ROSE (ROSE arm). The primary end point was the rate of the successful accomplishment of the institution's clinical protocol for molecular profiling of nonsquamous non-small cell lung cancer (EGFR and KRAS testing, followed by ALK testing for tumors with EGFR and KRAS wild-type status). RESULTS: Complete genotyping was achieved in 108 of 126 patients (85.7%) (90.8% in the ROSE arm vs 80.3% in the EBUS arm, P = .09). The patients in the ROSE arm were less likely to have samples that could be used only for pathologic diagnosis because of minimal tumor burden (0 vs 6, P = .05), and were more likely to have the bronchoscopy terminated after a single biopsy site (58.9% vs 44.1%, P = .01). CONCLUSIONS: ROSE prevents the need for a repeat invasive diagnostic procedure aimed at molecular profiling in at least one out of 10 patients with advanced lung cancer and significantly reduces the risk of retrieving samples that can be used only for pathologic subtyping because of minimal tumor burden. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01799382; URL: www.clinicaltrials.gov.

Unusual clinical presentation of thoracic tuberculosis: the need for a better knowledge of illness.

BACKGROUND: Pulmonary tuberculosis (TB), a highly contagious infectious disease, is a significant public health problem all over the world and remains an important cause of preventable death in the adult population. Endobronchial TB is an unusual form of thoracic TB that may be complicated by tracheobronchial stenosis, and bronchoesophageal fistula formation is a very rare complication. Tubercular lymphadenitis can also lead to fistula formation through a process of caseum necrosis and opening of a fistula between the bronchus and oesophagus. CASE REPORT: We report an uncommon case of thoracic TB in an immunocompetent 73-year-old Caucasian man who presented several problems: bronchoesophageal fistula, endobronchial TB, and mediastinal lymphadenopathy in the absence of contemporary parenchymal consolidation. Furthermore, he presented a normal chest radiograph and mostly unclear and non-specific symptoms at onset. CONCLUSIONS: We emphasize the need for a better knowledge of this illness and awareness that it may have an unusual presentation. In these cases, diagnosis and proper treatment can be delayed, with severe complications for the patient. Pulmonary TB remains a real diagnostic challenge: a normal chest radiograph and nonspecific symptoms do not allow us to exclude this persistent infectious disease.

Endobronchial ultrasound-guided transbronchial needle aspiration for diagnosis of sarcoidosis in clinically unselected study populations.

Literature suggests that ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has excellent performance characteristics for diagnosis of sarcoidosis. However, many authors challenge the external validity of EBUS-TBNA results, as most studies were performed in referral centres by highly experienced investigators, and included populations with very high sarcoidosis prevalence. We performed a systematic review and meta-analysis to estimate the role of EBUS-TBNA for diagnosis of sarcoidosis in studies enrolling consecutive patients with lymphadenopathy detected at imaging studies, regardless of the suspected underlying clinical aetiology. The Pubmed, Embase, Cinahl, Web of Science and Cochrane Library databases were screened to identify the pertinent literature. Quality of eligible studies was assessed by Quality Assessment, Data Abstraction and Synthesis-2 criteria. Pooled diagnostic yield, sensitivity and specificity were calculated, and a summary receiver operating characteristic curve was constructed. Subgroup analysis was planned to identify possible sources of study heterogeneity. Fourteen studies, collectively involving 2097 patients, fulfilled eligibility criteria. The median prevalence of sarcoidosis was 15%. EBUS-TBNA had a pooled diagnostic yield of 0.79 (standard deviation, 0.24), a pooled sensitivity of 0.84 (95% confidence interval (CI), 0.79-0.88) and a pooled specificity of 1.00 (95% CI, 0.99-1.00). Only subgroup analysis exploring the influence of study design seemed to influence the observed inter-study heterogeneity for sensitivity, retrospective studies showing worst sensitivity than prospective ones. The results of EBUS-TBNA for diagnosis of sarcoidosis in clinically unselected populations are excellent and compare favourably with published results from studies conducted in selected populations. High-quality trials would be needed to evaluate factors possibly explaining the observed heterogeneity in sensitivity.

CT pattern of lymphadenopathy in untreated patients undergoing bronchoscopy for suspected sarcoidosis.

BACKGROUND AND OBJECTIVE: Transbronchial needle aspiration procedures (TBNA, EBUS-TBNA) in sarcoidosis are associated with better results in stage I, and are preferentially performed in three lymph node stations (4R, 7, 11) as well as in the right mediastinal stations. We hypothesized that CT characteristics of lymphadenopathy, which were never systematically evaluated in untreated patients undergoing bronchoscopy for suspected sarcoidosis, could help explain the pattern of sampling and the different yield by radiographic stage of TBNA and EBUS-TBNA. METHODS: Number, size and location of lymph nodes were recorded in 74 consecutive sarcoidosis patients referred for biopsy, and were correlated with the radiographic stage. RESULTS: The mean number of stations harboring enlarged nodes was 8.05 per patient. Lymphadenopathy was more common in stations 7 (98.6% of patients), 11R (97.3%), 11L (86.5%), and 4R (79.7%). The overall mean size was 14.39 mm, but the largest mean size was documented in stations 7 (17.57 mm), 11R (16.83 mm), 8R (16.02 mm), and 4R (15.19 mm). The median [IQR] number of enlarged lymph node stations was significantly higher in the right than in the left mediastinum (2 [1-2] versus 0 [0-1], p < 0.001). No relationship was found between lymphadenopathy and sarcoidosis stage. CONCLUSIONS: The CT pattern of thoracic lymphadenopathy helps explain the excellent yield and the pattern of sampling of TBNA and EBUS-TBNA in sarcoidosis, but does not explain the higher yield associated with these procedures in stage I.

Sarcoidal granulomas in cytological specimens from intrathoracic adenopathy: morphologic characteristics and radiographic correlations.

BACKGROUND: Clinical experience and literature data suggest that the ability of pathologists to identify granulomas in cytological specimens from intrathoracic lymphadenopathy varies considerably and may negatively influence the yield of transbronchial needle aspiration (TBNA), both conventional and ultrasound-guided (EBUS-TBNA). OBJECTIVES: To describe the cytomorphology of sarcoidal granulomas on TBNA cytology specimens and to analyze the presence of associations between the cytological characteristics of granulomas and the radiographic stage of sarcoidosis. METHODS: TBNA cytological specimens from 123 sarcoidosis patients and 14 tuberculosis patients (control population) were reviewed independently by two pathologists blinded to the clinical-radiological details. RESULTS: Sarcoidal granulomas were small [median (IQR) largest diameter: 0.478 (0.318-0.701) mm] and well-formed, round or elliptical in shape, and almost invariably had a regular contour. Background elements lacked necrotic debris or exudate. The density [median (IQR) number of granulomas per slide: 6.85 (3.66-11) vs. 5.25 (2.5-8), p = 0.073] and size [median (IQR) largest diameter: 0.51 (0.319-0.733) vs. 0.398 (0.318-0.522), p = 0.071] tended to be larger in stage I than in stage II sarcoidosis. A necrotic background was common in the tuberculosis cohort studied (79 vs. 0%, p < 0.0001). CONCLUSIONS: Granulomas can be reliably identified on TBNA cytological material once their characteristic cytomorphology is delineated. A higher density of granulomas in lymphadenopathy of stage I sarcoidosis patients could partly explain the higher success rate constantly obtained by TBNA and EBUS-TBNA in this stage of the disease. A necrotic background suggests a tubercular etiology of the granulomas over a sarcoidal one, in the appropriate clinical setting.

Diffuse lung disease in neurofibromatosis.

Prevalence, characteristics and the very existence of neurofibromatosis-associated diffuse lung disease remain unclear, mostly because the few studies that looked at pulmonary involvement in such patients used chest X-ray as diagnostic mean. We report on the clinical, functional and HRCT findings in a patient with neurofibromatosis-associated diffuse lung disease and provide a short literature review.

Performance characteristics and predictors of yield from transbronchial needle aspiration in the diagnosis of peripheral pulmonary lesions.

BACKGROUND AND OBJECTIVE: Transbronchial needle aspiration (TBNA) is useful for diagnosing peripheral pulmonary lesions (PPL). However, TBNA is largely underused and the variables that may be related to its diagnostic usefulness have not been specifically studied. The aim of the present study was to evaluate the performance characteristics and predictors of yield from TBNA of PPL, and to compare the performance characteristics of different bronchoscopic sampling methods. METHODS: Consecutive patients with PPL were prospectively enrolled, and during the same examination, TBNA, transbronchial lung biopsy (TBLB) and bronchial washing (BW) were performed. RESULTS: Two hundred and eighteen PPL in 218 patients were sampled. TBNA was more sensitive (65%) than either TBLB (45%, P<0.001) or BW (22%, P<0.001). TBNA was the only diagnostic procedure in 42/196 patients (21%) with malignant lesions, and was more likely to be the only diagnostic procedure for lesions lacking (23/85 patients, 27%) than for lesions with the bronchus sign (19/111 patients, 17%). In multivariate analysis, a lesion size >2cm, malignancy and location in the middle lobe were independent predictors of a positive TBNA result. CONCLUSIONS: TBNA is the single best contributor to the success of bronchoscopy in the diagnosis of PPLs, and should be routinely used especially in the presence of lesions lacking the bronchus sign. Lesion size of > 2cm, location in the middle lobe, and malignant nature are strong predictors of a positive TBNA result.

Rapid on-site evaluation of transbronchial aspirates in the diagnosis of hilar and mediastinal adenopathy: a randomized trial.

BACKGROUND: Rapid on-site evaluation (ROSE) of transbronchial needle aspirates has long been used during flexible bronchoscopy, but its usefulness in the diagnosis of hilar and mediastinal adenopathy is controversial. The aim of the present study was to evaluate the extent to which ROSE can be valuable in patients undergoing transbronchial needle aspiration (TBNA) for the diagnosis of hilar and mediastinal adenopathy. METHODS: A total of 168 consecutive patients with enlarged lymph nodes were randomized to undergo TBNA with or without ROSE. The primary outcome measure of the study was the diagnostic yield of TBNA on a per-patient basis. Secondary outcome measures included the percentage of adequate specimens on a per-lymph node basis, the number of biopsy sites on a per-patient basis, and the complication rate of bronchoscopy on a per-patient basis. RESULTS: We found no significant difference between the TBNA group and the ROSE group in terms of diagnostic yield (75.3% vs 78.3%, respectively; P = .64), and percentage of adequate specimens (86.5% vs 78.4%, respectively; P = .11). The median (interquartile range) number of biopsy sites was significantly lower in the ROSE group (1 [1-2] vs 2 [1-2], respectively; P = .0005). The complication rate of bronchoscopy was significantly lower in patients undergoing on-site review (6% vs 20%; P = .01), whereas the complication rate of TBNA was similar among the study groups. CONCLUSIONS: ROSE of transbronchial aspirates from hilar and mediastinal nodes enables avoidance of additional biopsy without loss in diagnostic yield and reduces the complication rate of bronchoscopy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00915330; URL: www.clinicaltrials.gov