Collagen 3D matrices as a model for the study of cell behavior in pulmonary fibrosis.

Purpose: Idiopathic pulmonary fibrosis (IPF) is a complex progressive chronic lung disease where epithelial to mesenchymal interaction, extracellular matrix (ECM) contact, and pro-fibrotic cytokines dynamics take part in the development of the disease. The study of IPF in the widespread in vitro two-dimensional (2 D) culture fails to explain the interaction of cells with the changing environment that occurs in fibrotic lung tissue. A three-dimensional (3 D) co-culture model might shed light on the pathogenesis of IPF by mimicking the fibrotic environment. Materials and Methods: Fibroblasts from nine IPF were isolated and embedded in collagen matrices with the alveolar epithelial human cell line (A549) on the top. Cells were also cultured in 2 D with and without TGF-ß1 as a conventional model to compare with. Both types of cells were isolated separately. Protein and gene expression of the main fibrotic markers were measured by qPCR, Western blot, and ELISA. Results: IPF fibroblasts to myofibroblasts differentiation was observed in the 3 D model and in cells stimulated with TGF-ß1. In addition, ECM-related genes were highly up-regulated in the 3 D collagen matrix. A549 co-cultured 3 D with IPF fibroblasts showed EMT activation, with down-regulation of E-cadherin (CDH1). However, other pro-fibrotic genes as VIM, TGFB1, and MMP7 were up-regulated in A549 co-cultured 3 D with fibroblasts. Conclusions: 3 D-collagen matrices might induce fibroblasts' fibrotic phenotype as in the classic TGF-ß1 model, by up-regulating genes associated with matrix production. In addition, IPF lung fibroblasts seem to exert a pro-fibrotic influence in A549 cells when they are co-cultured. These results suggest that an improved 3 D co-culture model might serve as an important tool to study the fibrotic process and its regulation.

Outcomes of surgical resection after neoadjuvant chemoimmunotherapy in locally advanced stage IIIA non-small-cell lung cancer.

OBJECTIVES: This analysis aimed to evaluate perioperative outcomes of surgical resection following neoadjuvant treatment with chemotherapy plus nivolumab in resectable stage IIIA non-small-cell lung cancer. METHODS: Eligible patients received neoadjuvant chemotherapy (paclitaxel + carboplatin) plus nivolumab for 3 cycles. Reassessment of the tumour was carried out after treatment and patients with at least stable disease as best response underwent pulmonary resection. After surgery, patients received adjuvant treatment with nivolumab for 1 year. Surgical data were collected from the NADIM database and patient charts were reviewed for additional surgical details. RESULTS: Among 46 patients who received neoadjuvant treatment, 41 (89.1%) underwent surgery. Two patients rejected surgery and 3 did not fulfil resectability criteria. There were 35 lobectomies (85.3%), 3 of which were sleeve lobectomies (9.4%), 3 bilobectomies (7.3%) and 3 pneumonectomies (7.3%). Video-assisted thoracoscopy was the initial approach in 51.2% of cases, with a conversion rate of 19% (n = 4). There was no operative mortality at either 30 or 90 days. The most common complications were prolonged air leak (n = 8), pneumonia (n = 5) and arrhythmia (n = 4). Complete resection (R0) was achieved in all patients who underwent surgery, downstaging was observed in 37 patients (90.2%) and major pathological response in 34 patients (82.9%). CONCLUSIONS: Surgical resection following induction therapy with chemotherapy plus nivolumab appears to be safe and offers appropriate oncological outcomes. Perioperative morbidity and mortality rates in our study were no higher than previously reported in this setting. A minimally invasive approach is, therefore, feasible.

The Spanish Society of Pulmonology and Thoracic Surgery Lung Cancer Cooperative Group-II registry. A descriptive study.

INTRODUCTION AND OBJECTIVES: The seventh edition of the TNM classification, together with undeniable advantages, has limitations. The International Association for the Study of Lung Cancer (IASLC) Staging Committee has designed an international prospective study to improve this classification. A group of thoracic surgeons and pulmonologists was established in the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) Oncology area, and created a registry of new lung cancer (LC) cases to participate in this project. The aim of this paper is to describe the main characteristics of the patients included. MATERIALS AND METHODS: Prospective, observational, multicentre, multiregional data collection (epidemiological, clinical, therapeutic and, especially, anatomical extension) study, according to the IASLC protocol, to analyse its prognostic value. RESULTS: Two thousand, four hundred and nineteen patients (83.6% men) from 28 hospitals were included. Ninety-six percent of the men and 54% of the women were smokers or ex-smokers. Chest/abdominal computed tomography (CT) scanning was performed in over 90% and positron emission tomography (PET)/CT scanning in 51.5% of cases. Among the 1035 patients who underwent surgery, 77% had early stages (ia to iib), and 61.6% of those treated using other methods had stage iv. Respiratory comorbidity was higher in men (47.9% versus 21.4%). The most common histological subtype was adenocarcinoma (34%), especially in non-smoking women (69.5%). CONCLUSIONS: The proportion of women and adenocarcinomas, as well as those resected at an early stage, increased among LC cases in Spain.

Syncope and facial blushing due to giant intrapulmonary bronchogenic cyst.

A 43-year-old man presented with dizziness, head instability, and facial reddening, always in relation to body posture and without fever or systemic manifestations. Chest radiography revealed a large cavity with an air-fluid level in the right upper hemithorax. A right upper lobectomy was performed to remove a large bronchogenic cyst. The presentation with cardiac but no respiratory symptoms is uncommon but should be considered in the differential diagnosis of patients with intrathoracic cysts.