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.

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.

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.

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.

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.

Morphologic changes leading to bronchiolitis obliterans in a patient with delayed non-infectious lung disease after allogeneic bone marrow transplantation.

A 37-year-old man developed delayed non-infectious lung disease after undergoing bone marrow transplantation (BMT) for acute myeloid leukaemia. Over a 15-month period, the progression of morphologic changes from cellular interstitial pneumonia to bronchiolitis obliterans organizing pneumonia and cicatricial bronchiolitis obliterans was documented. Pulmonary function tests, high-resolution CT, bronchoalveolar lavage, lung biopsy and extensive microbiological studies were used as diagnostic tools either at onset and during the follow-up. This represents the first reported case in which a model--supported by longitudinal biopsy results--for the evolution of histologic lesions toward bronchiolitis obliterans after BMT is suggested; therapeutic implications are discussed.

Eosinophilic pleural effusion due to mesalamine. Report of a rare occurrence.

Mesalamine-induced lung toxicity has often been described. We report on a case of a patient who underwent mesalamine treatment, though in the absence of established criteria required for diagnosing Crohn's disease (CD) or ulcerative colitis (UC). He developed an adverse respiratory reaction to the drug, thus definitely proving its lung damaging capacity. The clinical presentation included eosinophilic pleural effusion, a feature never previously described in association with mesalamine intake.

Delayed non-infectious lung disease in allogeneic bone marrow transplant recipients.

BACKGROUND AND AIM OF THE WORK: The studies on late-onset non-infectious respiratory complications after allogeneic bone marrow transplantation (allo-BMT) have been mainly focused on bronchiolitis obliterans to date. The aim of this work was to analyze the incidence, clinico-pathologic characteristics and outcome of the entire spectrum of entities falling into the group of delayed non-infectious lung disease (DLD). METHODS: Retrospective chart review was carried out of 112 patients who underwent allo-BMT for hematologic malignancies between April 1995 and November 1998 at a single Institution. The categorization of the pulmonary disease was made by analyzing clinical data, bronchoalveolar lavage (BAL), high-resolution computed tomography (HRCT) and histology when possible. RESULTS: DLD occurred in 10 (10%) out of 97 recipients who survived at least 100 days following allo-BMT and was defined as bronchiolitis obliterans (BO; 4 cases), acute lung injury (ALI; 1 case) and subacute cellular interstitial pneumonia (SCIP; 5 cases). The BAL-profile was characterized by a marked increase of the neutrophil percentage in BO cases and of the lymphocyte (predominantly CD8+) percentage in parenchymal DLDs (SCIP, ALI). HRCT proved to be helpful to correctly identify BO cases, whereas histology was always needed to better define DLD presenting with an interstitial and/or alveolar pattern. The predominant airway involvement as well as the acute-onset of a respiratory illness with histological evidence of diffuse alveolar damage were associated with a worse prognosis because of a poor response to the immunosuppressive treatment. CONCLUSIONS: DLDs represent a group of entities heterogeneous in regard to variables such as onset and clinical behaviour (acute, subacute or chronic), predominant pattern of lung involvement (airway or parenchymal), response to treatment. Although immunopathologic mechanisms related to c-GVHD probably have a relevant pathogenic importance in this setting, the possible role of associated events (eg, drug toxicity and infections) at least in priming the lung damage need to be better clarified for its therapeutical implications.

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.

Evolution of physicians' attitudes towards practice guidelines.

OBJECTIVES: To assess changes in physicians' attitudes towards practice guidelines and towards the role of empirical evidence in their development. METHODS: The findings from two surveys carried out in 1993 and 1997 on the same random sample from two Italian medical specialty societies were compared. In both studies, physicians were mailed a questionnaire asking their views on the goals and role of practice guidelines in influencing clinical decision-making, and the role of empirical evidence versus subjective clinical experience in their development. RESULTS: One hundred and seventy physicians participated in both surveys. An increasing proportion of physicians accepted that cost containment could be a legitimate goal of practice guidelines (from 26% in 1993 to 40% in 1997; P = 0.010). More clinicians (43% in 1993 and 57% in 1997; P < 0.01) supported the use of empirical evidence, as opposed to subjective clinical experience, as the primary basis for practice guidelines. Although only a tiny minority of physicians (6% in 1993 and 1997) supported the view that practice guidelines should reflect patient preferences, an increased proportion of physicians supported the participation of representatives from outside the medical profession in their development. The level of support increased from 6% in 1993 to 26% in 1997 (P < 0.001) in the case of consumers, from 24% to 38% (P = 0.015) for patient involvement and from 16% to 33% (P = 0.003) in the case of health care administrators. CONCLUSIONS: The documented changes suggest that more clinicians acknowledge the role of empirical evidence and the need for a dialogue with other professionals and patient groups in the development of practice guidelines than was the case in the recent past.

On the crustacean hosts of larval acanthocephalan parasites of fishes from a coastal lagoon of River Po Delta.

A total of 4664 crustaceans of 2 species of gammarids (Gammarus insensibilis Stock, G. aequicauda Martynon) were collected and examined in search of larval helminth parasites. Larvae of Telosentis exiguus Von Linstow 1901 (Acanthocephala) were found in 6 out of 2806 G. insensibilis so far examined. This is the first record of an intermediate host for T. exiguus, of which a definitive host in Italy has already been indicated by us in Atherina boyeri.

[How have opinions of medical oncologists changed regarding compared guidelines? Findings from two surveys conducted in 1993-1997]. / Come sono cambiate le opinioni degli oncologici medici nei confronti delle linee-guida? Confronto tra i risultati di due studi condotti nel 1993 e 1997.

OBJECTIVES: To assess changes in physicians' attitudes toward practice guidelines and towards the role of empirical evidence in the development of recommendations for clinical practice. DESIGN: Comparison of findings from two surveys carried out in Italy in 1993 and 1997 on the same random sample of 300 physicians from two specialty societies dealing with cancer care. RESULTS: As for goals, the only change was the increasing (from 26% in 1993 to 40% in 1997; p = 0.010) number of physicians indicating cost containment. More clinicians (43% in 1993 vs 58% in 1997; p < 0.01) stated that guidelines should be based primarily on empirical evidence, rather than on clinical experience, and that the Ministry of Health should have a role in issuing guidelines (from 21% in 1993 to 46% in 1997; p < 0.001). Physicians supporting the participation of representatives from outside the medical profession in developing guidelines increased from 6% in 1993 to 26% in 1997 (p < 0.001) for consumers, from 24% to 38% (p = 0.015) for patients, and from 16% to 33% (p = 0.003) for health care administrators. CONCLUSIONS: Overall, these changes indicate that an increasing number of clinicians acknowledge the role of empirical evidence and the need for a confrontation with other professional and societal components as to what should be done in clinical practice.

[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.

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.