Prolonged remission of disseminated atypical adenomatous hyperplasia under gefitinib.

Abstract:Atypical adenomatous hyperplasia (AAH) is a putative precursor of bronchioloalveolar carcinoma (BAC) and adenocarcinoma of the lung, developing from terminal respiratory unit cells. AAH and BAC lesions typically present as ground-glass opacities at spiral chest computed tomography. Epidermal growth factor receptor polysomy/mutations, conferring higher sensitivity to Gefitinib, are frequent in BAC but less common in AAH. We describe an interesting case of disseminated AAH showing a sustained remission under Gefitinib therapy

Pulmonary availability of isotretinoin in rats after inhalation of a powder aerosol

Repeated oral administration of chemopreventive retinoids such as isotretinoin over extended periods of time is associated with intolerable systemic toxicity. Here isotretinoin was formulated as a powder aerosol, and its delivery to the lungs of rats was studied with the aim to explore the possibility of minimizing adverse effects associated with its oral administration. Rats received isotretinoin orally (0.5, 1 or 10 mg kg–1) or by inhalation (theoretical dose ~1 or ~10 mg kg–1) in a nose-only inhalation chamber. Isotretinoin was quantitated by high-pressure liquid chromatography in plasma and lung tissue. The ratios of mean area of concentration-vs-time curve (AUC) values in the lungs over mean AUCs in the plasma for isotretinoin following single or repeated aerosol exposure surpassed those determined for the oral route by factors of between two (single low-dose) and five (single high-dose). Similarly, the equivalent ratios for the maximal peak concentrations in lungs and plasma obtained after aerosol exposure consistently exceeded those seen after oral administration, suggesting that lungs were exposed to higher isotretinoin concentrations after aerosol inhalation than after oral administration of similar doses. Repeated high doses of isotretinoin by inhalation resulted in moderate loss of body weight, but microscopic investigation of ten tissues including lung and oesophagus did not detect any significant aerosol-induced damage. The results suggest that administration of isotretinoin via powder aerosol inhalation is probably superior to its application via the oral route in terms of achieving efficacious drug concentrations in the lungs. © 2000 Cancer Research Campaig

Toll-like receptor 3 as a new marker to detect high risk early stage Non-Small-Cell Lung Cancer patients

Immune and epithelial cells express TLR3, a receptor deputed to respond to microbial signals activating the immune response. The prognostic value of TLR3 in cancer is debated and no data are currently available in NSCLC, for which therapeutic approaches that target the immune system are providing encouraging results. Dissecting the lung immune microenvironment could provide new prognostic markers, especially for early stage NSCLC for which surgery is the only treatment option. In this study we investigated the expression and the prognostic value of TLR3 on both tumor and immune compartments of stage I NSCLCs. In a cohort of 194 NSCLC stage I, TLR3 immunohistochemistry expression on tumor cells predicted a favorable outcome of early stage NSCLC, whereas on the immune cells infiltrating the tumor stroma, TLR3 expression associated with a poor overall survival. Patients with TLR3-positive immune infiltrating cells, but not tumor cells showed a worse prognosis compared with all other patients. The majority of TLR3-expressing immune cells resulted to be macrophages and TLR3 expression associates with PD-1 expression. TLR3 has an opposite prognostic significance when expressed on tumor or immune cells in early stage NCSCL. Analysis of TLR3 in tumor and immune cells can help in identifying high risk stage I patients for which adjuvant treatment would be beneficial

Unexpected detection of SARS-CoV-2 antibodies in the prepandemic period in Italy

There are no robust data on the real onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and spread in the prepandemic period worldwide. We investigated the presence of SARS-CoV-2 receptor-binding domain (RBD)–specific antibodies in blood samples of 959 asymptomatic individuals enrolled in a prospective lung cancer screening trial between September 2019 and March 2020 to track the date of onset, frequency, and temporal and geographic variations across the Italian regions. SARS-CoV-2 RBD-specific antibodies were detected in 111 of 959 (11.6%) individuals, starting from September 2019 (14%), with a cluster of positive cases (>30%) in the second week of February 2020 and the highest number (53.2%) in Lombardy. This study shows an unexpected very early circulation of SARS-CoV-2 among asymptomatic individuals in Italy several months before the first patient was identified, and clarifies the onset and spread of the coronavirus disease 2019 (COVID-19) pandemic. Finding SARS-CoV-2 antibodies in asymptomatic people before the COVID-19 outbreak in Italy may reshape the history of pandemic

Pleural plaques in lung cancer screening by low-dose computed tomography : prevalence, association with lung cancer and mortality

Background: To report the prevalence of pleural plaques in a lung cancer screening trial by low-dose computed tomography (LDCT) and to test the association with incidence of lung cancer and mortality. Methods: The LDCT of 2303 screenees were retrospectively reviewed with the specific aim of describing the prevalence and features of pleural plaques. Self-administered questionnaire was used to assess asbestos exposure. Frequency of lung cancer, lung cancer mortality, and overall mortality were detailed according to presence of pleural findings. Statistical analyses included comparison of mean or median, contingency tables, and Cox model for calculation of hazard ratio (HR) and its 95% confidence interval (CI). Results: Among male screenees, 31/1570 (2%) showed pleural abnormalities, 128/1570 (8.2%) disclosed asbestos exposure, 23/31 (74.2%) subjects with pleural plaques consistently denied exposure to asbestos. There was a trend for higher frequency of lung cancer among subjects with pleural plaques (9.7% vs 4.2%). Lung cancer in subjects with pleural plaques was always diagnosed in advanced stage. Subjects with pleural plaques showed HR 5.48 (95% CI 1.61-18.70) for mortality from lung cancer. Conclusions: Pleural plaques are a risk factor for lung cancer mortality that can be detected in lung cancer screening by LDCT, also in subjects that are not aware of asbestos exposure. Trial registration