Diagnosis and treatment of early and locally advanced non-small-cell lung cancer: The 2019 AIOM (Italian Association of Medical Oncology) clinical practice guidelines.

The Italian Association of Medical Oncology (AIOM) has developed clinical practice guidelines for the diagnosis and treatment of patients with early and locally advanced non-small cell lung cancer. In the current paper a panel of AIOM experts in the field of thoracic malignancies discussed these topics, analyzing available scientific evidences, with the final aim of providing a summary of clinical recommendations, which may guide physicians in their current practice.

Treatment of advanced non-small-cell lung cancer: The 2019 AIOM (Italian Association of Medical Oncology) clinical practice guidelines.

The Italian Association of Medical Oncology (AIOM) has developed clinical practice guidelines for the treatment of patients with advanced non-small cell lung cancer (NSCLC). In the current paper a panel of AIOM experts in the field of thoracic malignancies discussed the available scientific evidences, with the final aim of providing a summary of clinical recommendations, which may guide physicians in their current practice.

Granular cell tumor of the trachea as a rare cause of dyspnea in a young woman.

Tracheal granular cell tumors are rare neurogenic neoplasms characterized by an indolent behavior. We report the case of a young woman affected by this tumor with non-specific clinical presentation. We performed a literature search in order to identify all the cases of tracheal granular cell tumor and to summarize the current state of knowledge about this rare disease.

The expanding role of endobronchial ultrasound in patients with centrally located intrapulmonary tumors.

OBJECTIVES: Tissue acquisition of lung tumors is crucial for diagnostic and treatment purposes. In patients with centrally located lung tumors without endobronchial abnormalities the yield of conventional bronchoscopy is poor. Objective of this study was to assess diagnostic yield of EBUS-TBNA in patients with lung tumors, located near or adjacent to the major airways. METHODS: International multicenter retrospective analysis (2013-2018) of linear EBUS databases in Bologna, Italy and Amsterdam, The Netherlands. Patients with a centrally-located lung tumor without endobronchial abnormalities who underwent lung tumor search with linear EBUS were included. Diagnostic yield, feasibility of EBUS guided tumor sampling, complication rate, adequacy of the aspirates for mutational analysis, and assessment of mediastinal/vascular invasion (T4) were evaluated. RESULTS AND CONCLUSION: Real-time EBUS-TBNA diagnostic yield to sample centrally located intrapulmonary tumor was 83% (136/163) and it was independent of tumor location (paratracheal, mainstem, lobar, segmental bronchus). The feasibility to sample the lung tumor was 89% (145/163). In 4 cases the tumor was not found with EBUS. In the other 14 cases, tumor sampling was not performed due to: loss of the echo window after needle insertion [n = 3], interposition of a large vessel [n = 7], switch to radial EBUS [n = 1], switch and sampling through EUS or EUS-B [n = 3]. No major complications occurred. Mutational analysis was successful in 54/63 (86%) of samples. Using surgery as reference standard, EBUS proved more reliable than CT (24/24, 100% versus 22/24, 91.7%, respectively) in the assessment of mediastinal/vascular tumor invasion (T4 status). IN CONCLUSION: Lung tumors presenting without endobronchial abnormalities and located adjacent to the major airways can be safely sampled by EBUS-TBNA resulting in high diagnostic yield irrespective of tumor location. Successful molecular profiling and reliable assessment of mediastinal/vascular invasion (T4) in patients with advanced disease provide additional value to EBUS procedures in the setting of centrally-located lung lesions.

Diagnostic bronchoscopy: state of the art.

Since the introduction of the flexible fibreoptic bronchoscope in the late 1960s there have been relatively few technological advances for three decades, aside from the development of a white light video bronchoscope with a miniature charge-coupled device built in its tip replacing the fibreoptics. White light flexible videobronchoscopy with its ancillary devices (forceps biopsy, bronchial brushing, bronchoalveolar lavage, bronchial washings and transbronchial needle aspiration) has long been the only established diagnostic bronchoscopic technique. With the advances in microtechnology over the past two decades, recent technical developments such as autofluorescence bronchoscopy and endoscopic ultrasound allow better evaluation of endobronchial, mediastinal and parenchymal lesions.

Granulomatous lung disease.

Granulomas are a frequent challenge for pathologists, which can be identified both in histological and cytological material in a number of conditions. With regard to interstitial lung diseases, granulomas can be associated with infection (e.g. mycobacterial), immunological conditions (e.g. hypersensitivity pneumonitis), or may be idiopathic (e.g. sarcoidosis). Considering morphology, features that should be identified are the presence of necrosis, the cohesiveness and coalescence of granulomas, the presence of fibrosis and the amount and quality of the associated inflammatory infiltrate. The most interesting approach to granulomatous lung disease is indeed represented by their pattern of distribution within the secondary lobule; in fact, granulomas can be distributed along lymphatic routes (e.g. sarcoidosis), randomly (miliary infections, e.g. mycobacterial and fungal infections), or along the airways (hypersensitivity pneumonitis, hot tub lung, aspiration pneumonia and sometimes infections). We propose a combined radiological-histopathological approach for defining the morphological features and anatomic localization of granulomatous ILDs. In addition, a detailed review of their clinical features is provided, together with a description of the main procedures used to obtain respiratory samples for pathology and microbiology studies in these patients.

Collapse of a new type of self-expanding metallic tracheal stent.

Alveolus TB-STS is a new self-expanding, completely polyurethane-covered, metallic stent which has been designed to be successfully used even in the treatment of non-neoplastic airway strictures as it is supposed to be removable. We recently observed the collapse of an Alveolus tracheal stent, causing dyspnea and hemopthysis, in a 63-yr-old female patient with post-intubation tracheal stenosis. Such a complication, which to our knowledge has never been previously reported with metallic stent use, forced us to remove the stent.

Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib.

BACKGROUND: The aim of the study was to assess whether loss of PTEN and expression of insulin-like growth factor receptor 1 (IGFR-1) could be responsible for intrinsic resistance to the tyrosine kinase inhibitor (TKI) gefitinib. PATIENTS AND METHODS: One hundred and twenty-four gefitinib-treated patients with advanced non-small-cell lung cancer (NSCLC) were analyzed for PTEN and IGFR-1 expression by immunohistochemistry. RESULTS: IGFR-1 was evaluated in 77 patients and resulted positive in 30 (39.0%). IGFR-1 expression was not significantly associated with clinical or biological characteristics. No difference in response to gefitinib treatment (16.7% versus 12.8%, P = 0.74) and time to progression (2.6 versus 3.06 months, P = 0.83) was observed between IGFR-1+ and IGFR-1-. Median survival was significantly longer in IGFR-1+ patients (17.8 versus 7.3 months, P = 0.013). PTEN expression was successfully evaluated in 93 cases. Loss of PTEN was detected in 19 tumors (20.4%) and was not associated with any clinical or biological characteristic. No difference in terms of response, time to progression and survival was observed between PTEN+ and PTEN- patients. In multivariable analysis IGFR-1 negative status was significantly associated with higher risk of death (hazard ratio 2.21, P = 0.012). CONCLUSIONS: IGFR-1 expression and loss of PTEN are not associated with intrinsic resistance to gefitinib. Clinical relevance of these two biomarkers as determinant for acquired resistance, and the prognostic role of IGFR-1 expression in patients not exposed to TKIs should be evaluated further.

Acute exacerbation of idiopathic pulmonary fibrosis: report of a series.

This study describes five cases presenting an acute clinical course of pulmonary fibrosis, in the absence of specific precipitating factors. A retrospective chart review of five patients with histologically proved usual interstitial pneumonia was carried out in 2001-2002. Clinical data, bronchoalveolar lavage (BAL) findings, high resolution computed tomography and histological features were reported. On admission all cases presented hypoxemia and dyspnoea, while some showed an increase of carbohydrate antigen 19.9 or laboratory tests typical of infection, although appropriate cultures were all negative. Altogether, four subjects died and only one is on follow-up. A pattern of diffuse ground-glass or alveolar opacification superimposed on reticular and linear findings was evident on lung imaging in all cases. Marked neutrophilia, together with type II reactive cells hyperplasia, was detected on BAL. Histological findings, from open lung biopsy or autopsy, showed all the aspects of usual interstitial pneumonia with superimposed features of acute lung injury, such as diffuse alveolar damage, with or without hyaline membranes, type II reactive cells hyperplasia and numerous fibroblastic foci. This study also underlines the diagnostic value of bronchoalveolar lavage versus open lung biopsy.

Acute interstitial pneumonia: report of a series.

Four cases of acute interstitial pneumonia (AIP) are described with special emphasis on clinical background, lung imaging and bronchoalveolar lavage findings. A retrospective chart review of four patients with histologically-proven AIP, diagnosed between 1998 and 2000, was carried out. Clinical data, bronchoalveolar lavage (BAL) findings, high-resolution computed tomography (HRCT) and histological features were analysed. Three patients died and only one is in follow-up. HRCT showed areas of ground glass attenuation and alveolar consolidation in all patients. Histology, documented by open lung biopsy or autopsy specimens, was consistent with the organising form of diffuse alveolar damage pattern. BAL findings were characteristic, with a huge neutrophilia associated with scattered atypical type II pneumocytes collected in clusters with extracellular amorphous material (fragments of hyaline membranes) observed in two out of three cases. In this paper, four cases of acute interstitial pneumonia are reported in detail. The poor prognosis associated with this entity has been confirmed and the possible diagnostic role of the bronchoalveolar lavage is emphasised.

Urinary desmosine excretion in acute exacerbations of COPD: a preliminary report.

Desmosine (DES) is an elastin-derived, cross-link amino acid, which is not metabolized; hence, its urinary levels reflect elastin breakdown. We hypothesized that elastin degradation should increase as a result of increased lung inflammation during an acute exacerbation of COPD and should decrease after recovery. To test this hypothesis we measured DES in three urine samples from nine COPD subjects during the first 5 days of an acute exacerbation and at 2 months after recovery. We also measured forced expiratory volume in 1 sec (FEV1) to monitor the effects ofthe exacerbation on ventilatory function. The mean (SD) FEV1 was 45 (15)% predicted during the exacerbation and 57.8 (16)% predicted 2 months later (P=0.00001). The mean (SD) DES excretion was 25.3 (9) microg g(-1) creatinine at day 1;23.5 (9) at day 3 and 24 (9) at day 5 of the exacerbation. The mean (SD) urinary DES excretion 60 days after discharge was 20.9 (7) microg g(-1) creatinine (P=0.049) in comparison with the mean of the three acute-phase values. The size of the increase in desmosine excretion during exacerbation is small, 3.2 microg g(-1) creatinine or 16% of the recovery desmosine value. We conclude that there is a small but statistically significant increase in lung elastin breakdown in the body during an acute exacerbation of COPD.

[Evaluation of the appropriateness of hospital use: the case of IRCCS Ospedale Maggiore di Milano, Italy]. / Valutazione dell'appropriatezza dell'attività di ricovero dell'Ospedale Maggiore di Milano IRCCS mediante l'utilizzo del metodo PRUO.

In 1999 an Italian version of the AEP was applied to some units of the IRCCS Ospedale Maggiore di Milano and a modified AEP version was used to evaluate the day hospital activity. The main aims of the study were: to establish the appropriateness of the utilisation of beds and of day hospital activity and to calculate the costing of the misuse of hospital resources. 267 admission days were evaluated and 31.5% were not appropriated; whereas of 3,248 days of stay 37% were found not appropriated. The day hospital activity was evaluated through 300 record referred to 570 days of treatment and 13% of them were not appropriated. The cost of the 1,201 not appropriated hospital days was over 351.000. The not appropriated level of hospital utilisation in the IRCCS Ospedale Maggiore di Milano is similar to what is reported in national and international literature. Our study highlights some limits in the application of the AEP protocol at high specialised hospital units.