Molecular testing on bronchial washings for the diagnosis and predictive assessment of lung cancer.

Cytopathological analyses of bronchial washings (BWs) collected during fibre-optic bronchoscopy are often inconclusive for lung cancer diagnosis. To address this issue, we assessed the suitability of conducting molecular analyses on BWs, with the aim to improve the diagnosis and outcome prediction of lung cancer. The methylation status of RASSF1A, CDH1, DLC1 and PRPH was analysed in BW samples from 91 lung cancer patients and 31 controls, using a novel two-colour droplet digital methylation-specific PCR (ddMSP) technique. Mutations in ALK, BRAF, EGFR, ERBB2, KRAS, MAP2K1, MET, NRAS, PIK3CA, ROS1 and TP53 and gene fusions of ALK, RET and ROS1 were also investigated, using next-generation sequencing on 73 lung cancer patients and 14 tumour-free individuals. Our four-gene methylation panel had significant diagnostic power, with 97% sensitivity and 74% specificity (relative risk, 7.3; odds ratio, 6.1; 95% confidence interval, 12.7-127). In contrast, gene mutation analysis had a remarkable value for predictive, but not for diagnostic, purposes. Actionable mutations in EGFR, HER2 and ROS1 as well as in other cancer genes (KRAS, PIK3CA and TP53) were detected. Concordance with gene mutations uncovered in tumour biopsies was higher than 90%. In addition, bronchial-washing analyses permitted complete patient coverage and the detection of additional actionable mutations. In conclusion, BWs are a useful material on which to perform molecular tests based on gene panels: aberrant gene methylation and mutation analyses could be performed as approaches accompanying current diagnostic and predictive assays during the initial workup phase. This study establishes the grounds for further prospective investigation.

An unusual case of acute respiratory failure in a patient with pulmonary veins stenosis late after catheter ablation of atrial fibrillation: a case report and the review of the literature.

BACKGROUND: Atrial fibrillation (AF) can be treated with percutaneous catheter ablation procedures into the left atrium. Pulmonary veins stenosis (PV) stenosis is a severe complication of this procedure. CASE PRESENTATION: we report a case of late hemoptysis secondary to severe PV stenosis in a man who underwent AF ablation 9 months before onset of symptoms. He presented four episodes of bleeding and developed an acute respiratory failure (ARF). Parameters of respiratory mechanics and medical investigation did not show any abnormalities. Only computed tomography (CT) angiography showed stenosis of 3 out of 4 native PVs. PV balloon dilatation in all affected PVs and a stent was implanted in 1 of the 3 PVs with full restoration of respiratory function during 1 year follow-up. CONCLUSION: PV stenosis may be the underlying cause of recurrent haemoptysis after AF ablation in the presence of normal respiratory parameters. This diagnosis can be confirmed by means of CT angiography and magnetic resonance imaging can provide accurate localization of stenosis.

Midazolam in flexible bronchoscopy premedication: effects on patient-related and procedure-related outcomes.

BACKGROUND: The role of midazolam in flexible bronchoscopy premedication has been debated. The aim of the present study was to evaluate whether midazolam premedication increases the patient-reported tolerance and the physician-reported or nurse-reported feasibility of bronchoscopy. METHODS: Randomized, double-blinded, placebo-controlled, 3-arm study. The study population included patients undergoing bronchoscopy for appropriate clinical indications. Patients were randomly assigned to receive 0.035 mg/kg intravenous midazolam (low dose), 0.07 mg/kg (high dose), or placebo. Vital parameters were monitored in continuum during the procedure. At the end of the procedure, the operating physician and assisting nurse filled out a questionnaire to score the procedure-related outcomes (satisfaction, feasibility, completeness, and unexpected events). Patients were asked to fill out a specific questionnaire to assess the patient-reported tolerance and satisfaction 2 hours after the bronchoscopy. RESULTS: A total of 100 patients (mean age 58.6±1.0; 57% male) were included in the study (33 in the low-dose midazolam group, 34 in the high-dose midazolam group, and 33 in the placebo group). The patient-reported tolerance score was significantly higher in the high-dose midazolam group than in the placebo group (P<0.01). No differences were found in the 3 groups in terms of the physician-reported feasibility and completeness of the procedure. In the groups of patients premedicated with midazolam, significant oxygen desaturation was recorded (at 10 and 8 min after the introduction of the bronchoscope) compared with the baseline value (P<0.01). CONCLUSIONS: In our study, premedication with midazolam increased the patient-reported tolerance of the bronchoscopy. However, the absence of premedication did not affect the diagnostic yield of the procedure.

[Chronic cough and worsening dyspnea: a case of idiopathic tracheal stenosis]. / Tosse cronica persistente e dispnea ingravescente: un caso di bronchite difficile.

We report a case of idiopathic tracheal stenosis in a 75-year-old woman, who presented to our observation with a diagnosis of asthmatic bronchitis characterized by cough and exertional dyspnea, later complicated by the appearance of tirage. Biopsy of the lesion showed focal squamous metaplasia of the epithelium lining, multiple sclerosis and chronic inflammatory infiltration of the corium. The patient was treated with endoscopic destruction via rigid bronchoscopy, through the combined action of YAG laser and mechanical debulking.

Primary Pulmonary Epithelioid Hemangioendothelioma: A Rare Cause of PET-Negative Pulmonary Nodules.

We report here a case of primary pulmonary epithelioid hemangioendothelioma diagnosed in a 67-year-old Caucasian man, presenting with exertion dyspnoea, dry cough, and multiple bilateral pulmonary nodules revealed by computed tomography. At the 18F-fluorodeoxyglucose positron emission tomography, these nodules were negative. The histopathological diagnosis was made on a pulmonary wedge resection (performed during video-thoracoscopic surgery).

Bronchoalveolar lavage in systemic sclerosis with lung involvement: role and correlations with functional, radiological and scintigraphic parameters.

To evaluate the role and the prognostic value of bronchoalveolar lavage (BAL) in scleroderma patients with interstitial lung disease. We reviewed the records of 79 patients with systemic sclerosis (SSc) who had dyspnea and pulmonary involvement and underwent BAL study. Sixty-two patients were prospectively followed up for 12-36 months and re-evaluated by pulmonary function tests (PFTs). Seventy-nine SSc patients were enrolled (71 F and 8 M), 55 with limited and 24 with a diffuse form; mean age 55 ± 13 years; mean disease duration 55.2 ± 59 months. All patients were ANA positive, of these 30 were anti-topoisomerase-1 positive (anti-Topo1) and 22 were anti-centromere positive (ACA). Thirty-one patients had alveolitis (39.2%) that was neutrophilic in 12 patients, eosinophilic in 3 and mixed (neutrophilic and eosinophilic) in 16 patients. Compared to patients without alveolitis, those with alveolitis had a significant reduction of carbon monoxide diffusing capacity (DLCO), forced vital capacity (FVC) and more elevated lung high-resolution computed tomography (HRCT) scores. Furthermore, alveolar clearance was significantly accelerated. No differences were found between patients with and without alveolitis regarding disease subsets (diffuse vs limited-SSc); a significant predominance of anti-Topo1 antibodies was found in the alveolitis group and of ACA antibodies in the non-alveolitis cohort. During the follow-up, (range: 12-36 months) 62 patients, 26 with and 36 without alveolitis were re-evaluated with PFTs. In the alveolitis group, 12 patients (46.1%) showed stable lung function parameters and 14 had worsened (53.8%). In this group, 20 patients (77%) received cyclophosphamide (CYC): 11 (55%) worsened (5 of them died of cardio-pulmonary complications) and 9 (45%) remained stable. Six patients could not be treated; of these 3 remained stable and 3 worsened. Among 36 patients with normal BAL, 11 (30.5%) showed stable lung function parameters, 13 improved (36.1%) and 12 worsened (33.3%); in this last group, 2 patients died of extra-pulmonary complications. Six patients, with progression of lung fibrosis, were treated with CYC: 3 of them improved and 3 remained stable. Our study revealed a trend toward a more severe course in the SSc patients with BAL alveolitis; probably the non-significant result is related to the low number of the examined subjects and to the selection criteria. However, BAL remains the only tool to exclude lung infections and, in our experience, a useful instrument to evaluate interstitial lung disease in SSc patients.

Bronchial carcinoid tumors: clinical and radiological correlation.

PURPOSE: To evaluate the incidence of bronchial carcinoid tumor (BCT) in population affected by various lung tumors, retrospectively reviewed between 1986-2001, and to emphasize the radiographic patterns if they are characteristic. MATERIALS AND METHODS: In the above mentioned period, chest x-ray and CT were performed in 1110 patients, both male and female, affected by lung neoplasms. RESULTS: 20 patients were affected by BCT (16 males, and 13 females), aged between 26 and 75 years (mean age 57.5), with histopathologic diagnosis of typical (9 cases, 31%) and atypical (20 cases, 69%) bronchial carcinoid tumors. Localized right lung lesion were as follows: 7 cases in superior, 9 in middle and 4 in inferior lobes; in the left lung, 5 cases in superior, and 4 in inferior lobes. Size of the lesions was as average 2.4 cm in diameter (with a range of 0.5-12 cm). On x-ray and CT images, BCT appeared as a well marginated nodule, of which 9 were peripheral and 20 central. DISCUSSION AND CONCLUSION: BCT are classified as neuroendocrine carcinomas,and are divided in typical and atypical forms, with variable grade of malignancy. Central neoplasms are symptomatic due to bronchial obstruction (i.e., pneumonia, atelectasis, bronchiectasis, emphysema and/or lung abscess); if airway obstruction is partial, then cough, wheezing and recurrent pulmonary infections occur. Peripheral tumors are generally asymptomatic and they are discovered occasionally, when chest x-ray is made for other reasons. Radiographic features are similar in typical and atypical BCT. In central tumors a rounded well circumscribed hilar mass is noted, with lobulated or bumpy margins. Central cavitation is not referred to. Peripheral BCT appear as a solitary nodule, inferioer then 3 cm in size, marginated, surrounded by normal pulmonary tissue. Signs and symptoms of BCT are evasive and vague. No current clinical or laboratory procedures are useful in confirming the diagnosis; particularly, no imaging modalities are able to differentiate between BCT and other pulmonary tumors. For this reason, a clinical radiologic endoscopic and histopathologic approach is necessary. CT is more sensiticve then conventional radiography, especially in detecting small lesions, calcification and enlarged lymph nodes. MRI may be useful in those patients, who cannot tolerate IV contrast media. Scintigraphy may be employed in discovering relapses and long standing metastases.