Breakthroughs in lung cancer management

In the present issue of Anales del Sistema Sanitario de Navarra, Rico et al summarize the progress in key areas of the radiotherapeutic strategies to fight against advanced lung cancer1. Progress in radiotherapy strategies for lung cancer management has been remarkable in the last decade. We will devote some comments in the present editorial to these achievements. Nevertheless, radiotherapy (RT) has been only one of the many areas that have benefited from successful basic, translational and clinical research in lung cancer during the last decade. In the following paragraphs, we will very briefly mention some of these breakthroughs and seminal achievements that have improved the survival prospects of lung cancer patients in the decade from 2010 to 2020

Radiologic features of small pulmonary nodules detected in initially negative screening CT examinations: a step towards personalized screening strategies?

Results of the National Lung Screening Trial (NLST) have invigorated the discussion around performing lung cancer screening using low-dose computed tomography (LDCT) of the chest. The NLST trial demonstrated a clear benefit of LDCT screening in reducing lung cancer and all-cause mortality, by showing reduced lung cancer mortality in high-risk individuals by about 20%, and allcause mortality by 6.7%, compared to a control group of subjects receiving chest radiographs

Adrenomedullin expression in a rat model of acute lung injury induced by hypoxia and LPS

Adrenomedullin (ADM) is upregulated independently by hypoxia and LPS, two key factors in the pathogenesis of acute lung injury (ALI). This study evaluates the expression of ADM in ALI using experimental models combining both stimuli: an in vivo model of rats treated with LPS and acute normobaric hypoxia (9% O2) and an in vitro model of rat lung cell lines cultured with LPS and exposed to hypoxia (1% O2). ADM expression was analyzed by in situ hybridization, Northern blot, Western blot, and RIA analyses. In the rat lung, combination of hypoxia and LPS treatments overcomes ADM induction occurring after each treatment alone. With in situ techniques, the synergistic effect of both stimuli mainly correlates with ADM expression in inflammatory cells within blood vessels and, to a lesser extent, to cells in the lung parenchyma and bronchiolar epithelial cells. In the in vitro model, hypoxia and hypoxia LPS treatments caused a similar strong induction of ADM expression and secretion in epithelial and endothelial cell lines. In alveolar macrophages, however, LPS-induced ADM expression and secretion were further increased by the concomitant exposure to hypoxia, thus paralleling the in vivo response. In conclusion, ADM expression is highly induced in a variety of key lung cell types in this rat model of ALI by combination of hypoxia and LPS, suggesting an essential role for this mediator in this syndrom

Effects of acute hypoxia and lipopolysaccharide on nitric oxide synthase-2 expression in acute lung injury

The potential role of nitric oxide synthase-2 (NOS2) in acute lung injury (ALI) has gained increasing attention. This study evaluates the effects of hypoxia, an important feature of ALI, on NOS2 expression in a rat model of ALI caused by exposure to hypoxia and LPS. Exposure to hypoxia alone had no effect on the expression of NOS2 in rat lungs. LPS treatment resulted in a significant increase in NOS2 in the lungs, which was further enhanced by concomitant exposure to hypoxia. Immunohistochemical analysis and in situ hybridization showed no changes in the expression of NOS2 in lung resident cells under any conditions. The increase in NOS2 levels is mainly due to the influx of NOS2-expressing inflammatory cells. By morphologic analysis, these inflammatory cells were identified as neutrophils, lymphocytes, and monocytes. In vitro experiments of lung epithelial and endothelial cell lines showed no detectable expression of NOS2 with any of the treatments. In a macrophage cell line, LPS-induced NOS2 expression was not affected by the concomitant exposure to hypoxia. In conclusion, LPS increases NOS2 expression in rat lungs through the recruitment of NOS2-producing leukocytes. Simultaneous exposure to LPS and hypoxia results in a greater influx of inflammatory cells that further enhances NOS2 expression

Preliminary Experience With the Use of Electromagnetic Navigation for the Diagnosis of Peripheral Pulmonary Nodules and Enlarged Mediastinal Lymph Nodes

Electromagnetic navigation is a new technique that can be used with bronchoscopy to obtain samples of small peripheral nodular lesions and enlarged mediastinal lymph nodes. It is very versatile in that it enables both transbronchial biopsies and fine-needle aspiration to be performed. We describe 2 cases in which navigation with the superDimension/ Bronchus system combined with traditional diagnostic techniques facilitated a definitive diagnosis by bronchoscopy. Electromagnetic navigation can obviate the need for more invasive diagnostic procedures such as surgery, thus saving time and money and avoiding complications

Effects of Small-Sided Games vs. Interval Training in Aerobic Fitness and Physical Enjoyment in Young Elite Soccer Players

The purpose of this study was to compare the effects of Small-Sided Games (SSG) vs. Interval Training (IT) in soccer training on aerobic fitness and physical enjoyment in youth elite soccer players during the last 8 weeks of the season. Seventeen U-16 male soccer players (age = 15.5 ? 0.6 years, and 8.5 years of experience) of a Spanish First Division club academy were randomized to 2 different groups for 6 weeks: SSG group (n = 9) and IT group (n = 8). In addition to the usual technical and tactical sessions and competitive games, the SSG group performed 11 sessions with different SSGs, whereas the IT group performed the same number of sessions of IT. Players were tested before and after the 6-week training intervention with a continuous maximal multistage running field test and the counter movement jump test (CMJ). At the end of the study, players answered the physical activity enjoyment scale (PACES). During the study, heart rate (HR) and session perceived effort (sRPE) were assessed. SSGs were as effective as IT in maintaining the aerobic fitness in elite young soccer players during the last weeks of the season. Players in the SSG group declared a greater physical enjoyment than IT (P = 0.006; ES = 1.86 ? 1.07). Coaches could use SSG training during the last weeks of the season as an option without fear of losing aerobic fitness while promoting high physical enjoyment.publishersversionPeer reviewe

Trasplante pulmonar

A lung transplant is usually the final therapeutic option for patients with respiratory insufficiency. In spite of the many advances in immunology and the management of complications, mortality and morbidity associated with this transplant are far higher than with others. Acute rejection is an almost universal problem in the first year, while obliterative bronchitis reduces long term survival. Respiratory infections also play a significant role in the complications associated with lung transplants due to the constant exposure of the graft to the outside. However, the success of this therapeutic option, which basically depends on a suitable selection of donor and recipient, are evident, above all with respect to quality of life

Use of Gene Therapy in a Subcutaneous Murine Model of Lung Cancer

OBJECTIVE: To assess the effectiveness of in vivo gene therapy to treat subcutaneous tumors generated from murine lung cancer cells. MATERIAL AND METHODS: C57BL/6 mice received subcutaneus injections of 5×105 cells from the murine Lewis lung cancer cell line. By 10 days, subcutaneous tumors of approximately 5 mm diameter were formed. At that point, treatment was provided by intratumor injection of a replication-defective recombinant adenovirus carrying the gene for thymidine kinase (AdCMV-Tk) or interleukin (IL) 12 (AdCMV-IL12), or by injection of syngeneic dendritic cells previously transduced with adenovirus containing the IL-12 gene (DC-IL12). Control groups were treated with saline or adenovirus containing the gene for β-galactosidase (AdCMV-LacZ), which functions as a reporter gene and does not have a therapeutic effect. The number of animals in each group ranged from 14 to 25 in experiments using adenovirus and from 10 to 12 in experiments using dendritic cells. Tumor size was followed for 3 weeks in the case of treatment with adenovirus and 4 weeks for treatment with dendritic cells. RESULTS: A significant reduction in subcutaneous tumor growth was observed in the groups treated with AdCMVTk, AdCMV-IL12, and DC-IL12 compared with control groups treated with saline or AdCMV-LacZ. The difference was statistically significant from day 7 of treatment in the AdCMV-Tk group, from day 9 in the AdCMV-IL12 group, and from day 10 in the DC-IL12 group, and in all cases it was maintained until the end of the follow-up period. CONCLUSIONS: Gene therapy with AdCMV-Tk, AdCMVIL12, or DC-IL12 is effective in our model of subcutaneous tumors arising from cells of the Lewis lung cancer cell line. The treatment leads to a significant reduction in tumor growth compared with control groups

Hyperleptinaemia, respiratory drive and hypercapnic response in obese patients

Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance to leptin has been consistently associated with obesity. Raised leptin levels have been reported in subjects with sleep apnoea or obesity-hypoventilation syndrome. The aim of the present study was to assess, by multivariate analysis, the possible association between respiratory centre impairment and levels of serum leptin. In total, 364 obese subjects (body mass index >or=30 kg.m(-2)) underwent the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), minute ventilation), fasting leptin levels, body composition and anthropometric measures. Subjects with airways obstruction on spirometry were excluded. Out of the 346 subjects undergoing testing, 245 were included in the current analysis. Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension, percentage body fat and minimal nocturnal saturation were predictors for baseline P(0.1). The hypercapnic response test was performed by 186 subjects; log leptin levels were predictors for hypercapnic response in males, but not in females. Hyperleptinaemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of the amount of body fat. These data suggest the extension of leptin resistance to the respiratory centre

Outpatient Management of Malignant Pleural Effusion Using a Tunneled Pleural Catheter: Preliminary Experience

Inpatient management of malignant pleural effusion includes the placement of a conventional thoracostomy tube for drainage and talc slurry pleurodesis and/or a surgical approach consisting of video-assisted thoracoscopic talc insufflation. Both techniques require prolonged hospital stays of up to 1 week. Unfortunately, life expectancy in patients with this disease does not usually exceed 6 months, and so the primary aim of any palliative intervention intended to improve quality of life should be to avoid hospital admissions and to relieve pain as far as possible. Of the few outpatient alternatives to hospital management the most frequently used is repeated thoracentesis. We describe the outpatient management of malignant pleural effusion by placement of a tunneled pleural catheter in a patient with stage IIIB lung adenocarcinoma. In our opinion, the use of this catheter offers a viable alternative to conventional therapy and is better tolerated