In recent years, there has been increased interest in the vascular component of airway remodelling in chronic bronchial inflammation, such as asthma and COPD, and in its role in the progression of ...disease. In particular, the bronchial mucosa in asthmatics is more vascularised, showing a higher number and dimension of vessels and vascular area. Recently, insight has been obtained regarding the pivotal role of vascular endothelial growth factor (VEGF) in promoting vascular remodelling and angiogenesis. Many studies, conducted on biopsies, induced sputum or BAL, have shown the involvement of VEGF and its receptors in the vascular remodelling processes. Presumably, the vascular component of airway remodelling is a complex multi-step phenomenon involving several mediators. Among the common asthma and COPD medications, only inhaled corticosteroids have demonstrated a real ability to reverse all aspects of vascular remodelling. The aim of this review was to analyze the morphological aspects of the vascular component of airway remodelling and the possible mechanisms involved in asthma and COPD. We also focused on the functional and therapeutic implications of the bronchial microvascular changes in asthma and COPD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract The tumor microenvironment can polarize innate immune cells to a proangiogenic phenotype. Decidual natural killer (dNK) cells show an angiogenic phenotype, yet the role for NK innate ...lymphoid cells in tumor angiogenesis remains to be defined. We investigated NK cells from patients with surgically resected non-small cell lung cancer (NSCLC) and controls using flow cytometric and functional analyses. The CD56+ CD16- NK subset in NSCLC patients, which represents the predominant NK subset in tumors and a minor subset in adjacent lung and peripheral blood, was associated with vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and interleukin-8 (IL-8)/CXCL8 production. Peripheral blood CD56+ CD16- NK cells from patients with the squamous cell carcinoma (SCC) subtype showed higher VEGF and PlGF production compared to those from patients with adenocarcinoma (AdC) and controls. Higher IL-8 production was found for both SCC and AdC compared to controls. Supernatants derived from NSCLC CD56+ CD16- NK cells induced endothelial cell chemotaxis and formation of capillary-like structures in vitro , particularly evident in SCC patients and absent from controls. Finally, exposure to transforming growth factor-β1 (TGFβ1 ), a cytokine associated with dNK polarization, upregulated VEGF and PlGF in peripheral blood CD56+ CD16- NK cells from healthy subjects. Our data suggest that NK cells in NSCLC act as proangiogenic cells, particularly evident for SCC and in part mediated by TGFβ1.
Video-assisted thoracic surgery (VATS) has become the standard for lung cancer diagnosis and treatment. However, this surgical technique requires specific and dedicated training. In the past 20 ...years, several simulator systems have been developed to promote VATS training. Advances in virtual reality may facilitate its integration into the VATS training curriculum. The present review aims to first provide a comprehensive overview of the simulators for thoracoscopic surgery, focused especially on simulators for lung lobectomy; second, it explores the role and highlights the possible efficacy of these simulators in the surgical trainee curriculum.
A literature search was conducted in the PubMed, EMBASE, Science Direct, Scopus and Web of Science databases using the following keywords combined with Boolean operators "AND" and "OR": virtual reality, VR, augmented reality, virtual simulation, mixed reality, extended reality, thoracic surgery, thoracoscopy, VATS, video-assisted thoracoscopic surgery, simulation, simulator, simulators, training, and education. Reference lists of the identified articles were hand-searched for additional relevant articles to be included in this review.
Different types of simulators have been used for VATS training: synthetic lung models (dry simulators); live animals or animal tissues (wet simulators); and simulators based on virtual or augmented reality. Their role in surgical training has been generally defined as useful. However, not enough data are available to ascertain which type is the most appropriate.
Simulator application in the field of medical education could revolutionize the regular surgical training curriculum. Further studies are required to better define their impact on surgeons' training programs and, finally, on patients' quality of care.
Despite some significant therapeutic breakthroughs leading to immunotherapy, a high percentage of patients with non-small cell lung cancer (NSCLC) do not respond to treatment on relapse, thus ...experiencing poor prognosis and survival. The unsatisfying results could be related to the features of the tumor immune microenvironment and the dynamic interactions between a tumor and immune infiltrate. Host–tumor interactions strongly influence the course of disease and response to therapies. Thus, targeting host-associated factors by restoring their physiologic functions altered by the presence of a tumor represents a new therapeutic approach to control tumor development and progression. In NSCLC, the immunogenic tumor balance is shifted negatively toward immunosuppression due to the release of inhibitory factors as well as the presence of immunosuppressive cells. Among these cells, there are myeloid-derived suppressor cells, regulatory T cells that can generate a tumor-permissive milieu by reprogramming the cells of the hosts such as tumor-associated macrophages, tumor-associated neutrophils, natural killer cells, dendritic cells, and mast cells that acquire tumor-supporting phenotypes and functions. This review highlights the current knowledge of the involvement of host-related factors, including innate and adaptive immunity in orchestrating the tumor cell fate and the primary resistance mechanisms to immunotherapy in NSCLC. Finally, we discuss combinational therapeutic strategies targeting different aspects of the tumor immune microenvironment (TIME) to prime the host response. Further research dissecting the characteristics and dynamic interactions within the interface host–tumor is necessary to improve a patient fitness immune response and provide answers regarding the immunotherapy efficacy, with the aim to develop more successful treatments for NSCLC.
•We tested the EORTC QLQ-C30 SumScore in a large lung cancer patient’s population.•HRQOL after surgery is worse compared the preoperative values.•The Summary Score is more sensitive than the General ...Health Score.•The SumScore can be used as a parsimonious patient-reported-outcome measure.
We tested the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) summary score (SumSC) to detect changes in the HRQOL after Non-small-cell lung cancer (NSCLC) surgery and compared its performance to the traditional scales.
EORTC QLQ-C30 data was obtained from 326 consecutive pre-operative patients submitted for anatomical lung resections for NSCLC.66 patients completed post-operative assessments 3 months after surgery. The data was analysed to evaluate the ability of the SumSC compared to the traditional scales to 1 preoperatively differentiate between clinical groups 2; detect post-op changes and to 3 compare pre and post-op changes in clinically different groups.The importance of perioperative changes was measured by calculating the effect size (ES).
Of the 326 patients, those older than 70 years, with higher DLCO value and Performance Status (PS) ≤1 had a significantly better preoperative SumScore.
Physical function (PF) showed a large and significant decline (ES 0.91). Role and social function also showed a significant and medium decline (ES 0.62 and 0.41).
Postoperatively some symptoms scales showed significant increases in the values, implying worse symptoms with the largest increase in dyspnoea (ES -0.88). The change in General Health score (GH) was not significant after surgery (ES 0.26, p = 0.062).
The SumSc, decreased significantly postoperatively. In particular, medium or large postoperative declines of SumSc were observed in both males and females, in patients with lower FEV1, lower performance score, and in those older than 70 years. Interestingly the decline of SumSc was observed irrespective of the preoperative DLCO level.
The Summary Score was more sensitive to changes in subjects' HRQOL, than the GH score. The SumSc can be used as a parsimonious and easy to interpreted patient-reported-outcome measure in multi-institutional database and future clinical trials.
Studies investigating microRNAs as potential biomarkers for cancer, immune-related diseases, or cardiac pathogenic diseases, among others, have exponentially increased in the last years. In ...particular, altered expression of specific miRNAs correlates with the occurrence of several diseases, making these molecules potential molecular tools for non-invasive diagnosis, prognosis, and response to therapy. Nonetheless, microRNAs are not in clinical use yet, due to inconsistencies in the literature regarding the specific miRNAs identified as biomarkers for a specific disease, which in turn can be attributed to several reasons, including lack of assay standardization and reproducibility. Technological limitations in circulating microRNAs measurement have been, to date, the biggest challenge for using these molecules in clinical settings. In this review we will discuss pre-analytical, analytical, and post-analytical challenges to address the potential technical biases and patient-related parameters that can have an influence and should be improved to translate miRNA biomarkers to the clinical stage. Moreover, we will describe the currently available methods for circulating miRNA expression profiling and measurement, underlining their advantages and potential pitfalls.
Atrial fibrillation (AF) after thoracic surgery is a continuing source of morbidity and mortality. The effect of postoperative AF on long-term survival however has not been studied. Our aim was to ...evaluate the impact of AF on early outcome and on survival > 5 years after pulmonary lobectomy for lung cancer.
From 1996 to June 2009, 454 consecutive patients undergoing lobectomy for lung cancer were enrolled and followed-up until death or study end (October 2010). Patients with postoperative AF were identified; AF was investigated with reference to its predictors and to short- and long-term survival (> 5 years).
Hospital mortality accounted for 7 patients (1.5%), while postoperative AF occurred in 45 (9.9%). Independent AF predictors were: preoperative paroxysmal AF (odds ratio OR 5.91; 95%CI 2.07 to 16.88), postoperative blood transfusion (OR 3.61; 95%CI 1.67 to 7.82) and postoperative fibro-bronchoscopy (OR 3.39; 95%CI 1.48 to 7.79). Patients with AF experienced higher hospital mortality (6.7% vs. 1.0%, p = 0.024), longer hospitalization (15.3 ± 10.1 vs. 12.2 ± 5.2 days, p = 0.001) and higher intensive care unit admission rate (13.3% vs. 3.9%, p = 0.015). The median follow-up was 36 months (maximum: 179 months). Among the 445 discharged subjects with complete follow-up, postoperative AF was not an independent predictor of mortality; however, among the 151 5-year survivors, postoperative AF independently predicted poorer long-term survival (HR 3.75; 95%CI 1.44 to 9.08).
AF after pulmonary lobectomy for lung cancer, in addition to causing higher hospital morbidity and mortality, predicts poorer long-term outcome in 5-year survivors.
Purpose
To establish the feasibility of performing percutaneous biopsy of lung lesions guided by fusion PET/CT-CBCT and to evaluate whether the metabolic information provided by a prior PET/CT scan ...add incremental benefits for diagnosis.
Methods
We retrospectively reviewed data from 180 patients who underwent CBCT-guided lung biopsy (group 1—90 cases) or PET/CT-CBCT fusion-guided lung biopsy (group 2—90 cases). Technical and clinical success was calculated. We also evaluated the agreement between biopsy and definitive histology and the possibility to carrying out immunehistochemical and molecular biology analyses.
Results
Technical success was achieved in 84/90 (93.3%) cases for group 1 and 89/90 (98.9%) for group 2 cases (
p
0.054). Clinical success was achieved in 80/94 (95.2%) cases for group 1 and 88/89 (98.9%) cases for group 2. Sensitivity, specificity, positive and negative predictive values and accuracy rate were, respectively, 94.5%, 100.0%, 100.0%, 73.3% and 95.2% for group 1 and 98.6%, 100.0%, 100.0%, 94.4% and 98.9% for group 2 (
p
0.167). Agreement between biopsy and definitive histology was reached in 85.7% for group 1 and in 96.2% for group 2 (
p
0.211). Immunohistochemical and molecular biology investigations were possible in 66.7% for group 1 and in 77.0% for group 2 (
p
0.297). No major complication occurred.
Conclusions
PET/CT-CBCT-guided lung biopsy is a feasible technique. In our retrospective case series, we found a higher clinical success rate, but no statistical difference was found.
In the COVID-19 era the tracheal complications due to prolonged mechanical ventilation have significantly increased. Acquired tracheoesophageal fistula is one of those in ventilated COVID-19 ...patients. Thus, the knowledge of their management in such fragile patient is crucial. We report a case of tracheoesophageal fistula in a 56-year-old female under prolonged mechanical ventilation for COVID-19 bilateral pneumonia and discuss its management. A surgical approach was proposed. By a collar-shaped transverse cervicotomic access, we transected the trachea at level of fistula en-bloc with the tracheostoma. The esophageal lesion was longitudinally repaired in two-layers. Protective left strap muscle was sandwiched between esophagus and trachea. The tracheal end-to-end anastomosis was completed without a re-tracheostoma. Even if surgical approach of tracheoesophageal fistula in COVID-19 patients has not been tested before, surgery remains the treatment of choice according to the multidisciplinary board.
Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH ...production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and β-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid.
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