Comparison of Bisulfite Pyrosequencing and Methylation-Specific qPCR for Methylation Assessment.

Different methodological approaches are available to assess DNA methylation biomarkers. In this study, we evaluated two sodium bisulfite conversion-dependent methods, namely pyrosequencing and methylation-specific qPCR (MS-qPCR), with the aim of measuring the closeness of agreement of methylation values between these two methods and its effect when setting a cut-off. Methylation of tumor suppressor gene p16/INK4A was evaluated in 80 lung cancer patients from which cytological lymph node samples were obtained. Cluster analyses were used to establish methylated and unmethylated groups for each method. Agreement and concordance between pyrosequencing and MS-qPCR was evaluated with Pearson's correlation, Bland-Altman, Cohen's kappa index and ROC curve analyses. Based on these analyses, cut-offs were derived for MS-qPCR. An acceptable correlation (Pearson's R2 = 0.738) was found between pyrosequencing (PYRmean) and MS-qPCR (NMP; normalized methylation percentage), providing similar clinical results when categorizing data as binary using cluster analysis. Compared to pyrosequencing, MS-qPCR tended to underestimate methylation for values between 0 and 15%, while for methylation >30% overestimation was observed. The estimated cut-off for MS-qPCR data based on cluster analysis, kappa-index agreement and ROC curve analysis were much lower than that derived from pyrosequencing. In conclusion, our results indicate that independently of the approach used for estimating the cut-off, the methylation percentage obtained through MS-qPCR is lower than that calculated for pyrosequencing. These differences in data and therefore in the cut-off should be examined when using methylation biomarkers in the clinical practice.

Predictive value of a series of inflammatory markers in COPD for lung cancer diagnosis: a case-control study.

BACKGROUND: There is a relationship between Chronic Obstructive Pulmonary Disease (COPD) and the development of lung cancer (LC). The aim of this study is to analyse several blood markers and compare their concentrations in patients with only COPD and LC + COPD. METHODS: Case-control study with cases presenting combined LC and COPD and two control groups (patients presenting only COPD and patients presenting only LC). We also included LC patients with descriptive purposes. In both groups, peripheral blood analyses of TNF-α, IL-6, IL-8, total leukocyte, lymphocyte and neutrophil counts, neutrophil-to-lymphocyte ratio, total platelet count, mean platelet volume, platelet-to-lymphocyte ratio, alpha 1-antitripsin (A1AT), IgE, C-reactive protein, fibrinogen, cholesterol and bilirubin were performed. We developed univariate and multivariate analyses of these markers, as well as a risk score variable, and we evaluated its performance through ROC curves. RESULTS: We included 280 patients, 109 cases (LC + COPD), 83 controls (COPD) and 88 LC without COPD. No differences were observed in the distribution by sex, age, BMI, smoking, occupational exposure, lung function, GOLD stage or comorbidity. Patients with LC + COPD had significantly higher levels of neutrophils [OR 1.00 (95%CI 1.00-1.00), p = 0.03] and A1AT [OR 1.02 (95%CI 1.01-1.03), p = 0.003] and lower cholesterol levels [OR 0.98 (95%CI 0.97-0.99), p = 0.009] than COPD controls. We developed a risk score variable combining neutrophils, A1AT and cholesterol, achieving a sensitivity of 80%, a negative predictive value of 90.7% and an area under the curve of 0.78 (95%CI 0.71-0.86). CONCLUSIONS: COPD patients who also have LC have higher levels of neutrophils and A1AT and lower of cholesterol. These parameters could be potentially predicting biomarkers of LC in COPD patients.

Lung cancer risk and do-it-yourself activities. A neglected risk factor for lung cancer.

BACKGROUND: The aim of this study was to assess the relationship between do-it-yourself activities entailing the exposure to carcinogenic substances and the risk of lung cancer. METHODS: We pooled individual data from different case-control studies conducted in Northwestern Spain which investigated residential radon and lung cancer. Cases had an anatomopathologically confirmed primary lung cancer and controls were selected at the pre-surgery unit with uncomplicated surgeries. Both cases and controls were older than 30 years with no previous cancer history. All participants were interviewed face-to-face using a specific questionnaire. Painting, model building, furniture refinishing and woodworking or home carpentry were the do-it-yourself activities considered risky due to exposure to carcinogenic agents. RESULTS: We included 1528 cases and 1457 controls. Practicing do-it-yourself risk activities was more frequent among cases: 16.0% were exposed to carcinogenic exposures during leisure time, compared to 11.8% for controls. The overall adjusted OR for lung cancer risk among individuals who practiced do-it-yourself risk activities, was 1.77 (95% CI: 1.36-2.31); this was 2.17 (95% CI: 1.51-3.11) when the analysis was restricted to individuals who performed these activities for at least 10 years. These risks were greater when the analyses were carried out exclusively among never-smokers, with the respective ORs being 2.04 (95% CI: 1.38-3.01) and 3.10 (95% CI: 1.78-5.40). CONCLUSION: These results support the hypothesis that do-it-yourself activities involving exposure to certain carcinogens are associated with an increased risk of lung cancer, both in ever and never-smokers.

Lung cancer and residential radon in never-smokers: A pooling study in the Northwest of Spain.

BACKGROUND: Using a pooled case-control study design, including only never-smokers, we have assessed the association of residential radon exposure with the subsequent occurrence of lung cancer. We also investigated whether residential radon poses a different risk specifically for adenocarcinoma. METHODS: We pooled individual data from different case-control studies conducted in recent years in Northwestern Spain which investigated residential radon and lung cancer. All participants were never-smokers. Cases had a confirmed biopsy of primary lung cancer. Hospital controls were selected at pre-surgery units, presenting for non-complex surgical procedures. They were interviewed using a standardized instrument. Residential radon was measured using alpha track detectors at the Galician Radon Laboratory at the University of Santiago de Compostela. RESULTS: A total of 1415 individuals, 523 cases and 892 controls were included. We observed an odds ratio of 1.73 (95%CI: 1.27-2.35) for individuals exposed to ≥ 200 Bq/m3 compared with those exposed to ≤100 Bq/m3. Lung cancer risk for adenocarcinoma was 1.52 (95%CI: 1.14-2.02) using the same categories for radon exposure. CONCLUSIONS: Residential radon is a clear risk factor for lung cancer in never-smokers. Our data suggest that radon exposure is associated with all histological types of lung cancer and also with adenocarcinoma, which is currently the most frequent histological type for this disease.

Predictive factors and prognostic effect of telomere shortening in pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: The abnormal shortening of telomeres is a mechanism linking ageing to idiopathic pulmonary fibrosis (IPF) that could be useful in the clinical setting. The objective of this study was to identify the IPF patients with higher risk for telomere shortening and to investigate the outcome implications. METHODS: Consecutive Spanish patients were included at diagnosis and followed up for 3 years. DNA blood samples from a Mexican cohort were used to validate the results found in Spanish sporadic IPF. Prior to treatment, telomere length was measured through quantitative polymerase chain reaction (qPCR) and Southern blot. Outcome was assessed according to mortality or need for lung transplantation. A multivariate regression logistic model was used for statistical analysis. RESULTS: Family aggregation, age of <60 years and the presence of non-specific immunological or haematological abnormalities were associated with a higher probability of telomere shortening. Overall, 66.6% of patients younger than 60 years with telomere shortening died or required lung transplantation, independent of functional impairment at diagnosis. By contrast, in patients older than 60 years with telomere shortening, the negative impact of telomere shortening in outcome was not significant. CONCLUSION: Our data indicate that young sporadic IPF patients (<60 years) with some non-specific immunological or haematological abnormalities had higher risk of telomere shortening, and furthermore, they presented a poorer prognosis.

Chronic Obstructive Pulmonary Disease in Lung Cancer Patients: Prevalence, Underdiagnosis, and Clinical Characterization.

BACKGROUND: Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are associated with increased morbidity and mortality. The differential clinical and functional features among LC patients with or without COPD have not been defined. OBJECTIVES: The aims of this study were to examine the prevalence and underdiagnosis rate of COPD in LC patients and to compare the clinical and functional features of LC patients with and without COPD. METHODS: We designed a multicenter hospital-based study including all LC cases diagnosed from January 2014 to August 2016. We assessed epidemiological, clinical, radiological, functional, and histological variables in all cases. RESULTS: We recruited 602 patients with LC, most of them men (77.9%), with a median age of 67 ± 15 years. The COPD prevalence among LC patients was 51.5%, with a underdiagnosis rate of 71.6%. The LC+COPD patients were older and the proportion of men was higher compared with the LC-only patients. The LC+COPD patients had more pack-years, more squamous LC, a lower monoxide transfer coefficient (KCO), and higher Charlson index scores than patients with LC only. The median survival of LC-only patients was 37% longer than that of LC+COPD patients (22 vs. 16 months), but this difference was not statistically significant. CONCLUSIONS: Among LC patients, COPD is prevalent and underdiagnosed. Patients with LC+COPD more often have squamous LC, have greater comorbidities, and have a lower KCO. More effort should be made for an early diagnosis of COPD to select patients at higher risk of developing LC.

Alcohol consumption and lung cancer risk in never smokers: a pooled analysis of case-control studies.

Background: Lung cancer is the deadliest cancer in developed countries but the etiology of lung cancer risk in never smokers (LCRINS) is largely unknown. We aim to assess the effects of alcohol consumption, in its different forms, on LCRINS. Methods: We pooled six multi-center case-control studies developed in the northwest of Spain. Cases and controls groups were composed of never smokers. We selected incident cases with anatomopathologically confirmed lung cancer diagnoses. All participants were personally interviewed. We performed two groups of statistical models, applying unconditional logistic regression with generalized additive models. One considered the effect of alcohol type consumption and the other considered the quantity of each alcoholic beverage consumed. Results: A total of 438 cases and 863 controls were included. Median age was 71 and 66, years, respectively. Adenocarcinoma was the predominant histological type, comprising 66% of all cases. We found that any type of wine consumption posed an OR of 2.20 OR 95%CI 1.12-4.35), and spirits consumption had an OR of 1.90 (95%CI 1.13-3.23). Beer consumption had an OR of 1.33 (95%CI 0.82-2.14). These results were similar when women were analyzed separately, but for men there was no apparent risk for any alcoholic beverage. The dose-response analysis for each alcoholic beverage revealed no clear pattern. Conclusions: Wine and spirits consumption might increase the risk of LCRINSs, particularly in females. These results have to be taken with caution given the limitations of the present study.

Residential radon, EGFR mutations and ALK alterations in never-smoking lung cancer cases.

The aim of this study was to assess if residential radon exposure might cause EGFR mutations or ALK rearrangements in never-smokers.We designed a multicentre case-control study in a radon-prone area (Galicia, Spain); only lung cancer cases were included in the study. We obtained residential radon measurements and clinical information for all the participants. We compared the median values of residential radon between patients with EGFR mutations or ALK rearrangements versus those without them.323 patients were included. Median age was 70 years and 19.5% were males. 42 and 15% of patients were EGFR- and ALK-positive, respectively. The most frequent EGFR alterations were exon 19 deletions and exon 21 (L858R) single-point substitution mutations. ALK-positive patients were 10 years younger than ALK-negative patients. Residential radon levels were two-fold higher in patients with exon 19 deletions compared with patients with exon 21 (L858R) single-point substitution mutations (216 versus 118 Bq·m-3; p=0.057). There were no differences in residential radon levels by EGFR mutation status. ALK-positive patients (n=12) essentially had two-fold residential radon levels compared with ALK-negative patients (290 versus 164 Bq·m-3, respectively).Residential radon may have a role in the molecular signature of lung cancer in never-smokers, although more studies with larger sample sizes are needed to support this hypothesis.

Small cell lung cancer in never-smokers.

Our aim was to describe the characteristics of a case-series of never-smoker small cell lung cancer (SCLC) cases.Cases of SCLC were selected from a prospective, multicenter, hospital-based case-control study performed in Spain. Participants were never-smokers older than 30 years with an anatomo-pathological confirmation of primary lung cancer. We collected clinical and epidemiological variables according to the study's protocol.We included 19 SCLC cases, 18 females (94.7%), median age 75 years (interquartile range (IQR) 70-80 years). Median residential radon concentration was 195 Bq·m(-3) (IQR 130-229 Bq·m(-3)). 10 patients had limited disease and nine had extended disease. Median survival was 242 days (IQR 94-496 days); 1- and 2-year survival were 36.8% and 17.6%, respectively. Survival was much higher for individuals with limited disease than for those with extended disease (median 336 versus 235 days; 1-year survival 50% versus 22.2% and 2-year survival 27% versus 0%, respectively). Performance status at diagnosis was closely related to survival.SCLC is an infrequent, highly aggressive disease in never-smokers. Survival is poor, even for limited disease. Age at diagnosis in SCLC is higher than that observed for never-smokers with adenocarcinoma. Residential radon exposure is higher than the action levels recommended by the World Health Organization.

A Pseudo-Outbreak of Pseudomonas putida and Stenotrophomonas maltophilia in a Bronchoscopy Unit.

BACKGROUND: Endoscopes represent the medical devices most commonly linked to health care-associated outbreaks and pseudo-outbreaks. Most of the recent outbreaks and pseudo-outbreaks have resulted from contaminated automated endoscope reprocessors (AER) or the use of damaged or malfunctioning bronchoscopes or contaminated equipment. OBJECTIVES: We investigated a pseudo-outbreak of Pseudomonas putida and Stenotrophomonas maltophilia recovered from bronchial washing (BW) specimens obtained during bronchoscopy in a bronchoscopy unit. METHODS: Samples were obtained from environmental surfaces in the endoscopy suite, bronchoscopes, and bronchoscopic dispensable material, and specimens of cleaning solutions, cleaning brushes, the AER, and the ultrasound system were sent for bacterial culture. Medical records were reviewed to identify possible infections after a bronchoscopy. RESULTS: P. putida and S. maltophilia were isolated from BW samples of 39 patients. The bronchoscopy models Olympus BF-1T160 and BF-160 were contaminated. Both bronchoscopes and other contaminated material (cleaning brushes, diluted cleaning solutions, and the sink) were isolated, but new cases continued to appear. The AER was recently installed, and new connections were used for the water lines and new tubes were connected to the AER. Initially, specimens were obtained from the external circuits and the internal walls of the AER. Finally, cultures were made from the filters on the water lines, and growth of P. putida and S. maltophilia was found. The investigation revealed that the BW specimens were contaminated because sterile saline was injected by means of the biopsy port of the bronchoscope and was recovered through the same channel by means of the proximal suction port. No patients developed clinical signs or symptoms of infection, but the positive cultures did lead to treatment of 21 patients. CONCLUSIONS: We described a pseudo-outbreak related to a contaminated bronchoscope because of inadequate installation of the AER for used new water lines and because the new tubes were connected to the AER. The antibacterial filters of the AER used tap water, and this may have contained low levels of microorganisms. No serious clinical complications derived from this pseudo-outbreak.

Lung cancer in never-smokers: a case-control study in a radon-prone area (Galicia, Spain).

The aim of the study was to assess the effect of residential radon exposure on the risk of lung cancer in never-smokers and to ascertain if environmental tobacco smoke modifies the effect of residential radon. We designed a multicentre hospital-based case-control study in a radon-prone area (Galicia, Spain). All participants were never-smokers. Cases had an anatomopathologically confirmed primary lung cancer and controls were recruited from individuals undergoing minor, non-oncological surgery. Residential radon was measured using alpha track detectors. We included 521 individuals, 192 cases and 329 controls, 21% were males. We observed an odds ratio of 2.42 (95% CI 1.45-4.06) for individuals exposed to ≥200 Bq·m(-3) compared with those exposed to <100 Bq·m(-3). Environmental tobacco smoke exposure at home increased lung cancer risk in individuals with radon exposure>200 Bq·m(-3). Individuals exposed to environmental tobacco smoke and to radon concentrations>200 Bq·m(-3) had higher lung cancer risk than those exposed to lower radon concentrations and exposed to environmental tobacco smoke. Residential radon increases lung cancer risk in never-smokers. An association between residential radon exposure and environmental tobacco smoke on the risk of lung cancer might exist.

Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study.

We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78-2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93-5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer.

Is the diagnostic yield of mediastinal lymph node cryobiopsy (cryoEBUS) better for diagnosing mediastinal node involvement compared to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)? A systematic review.

INTRODUCTION: New tools such as cryobiopsy of mediastinal lymph nodes (cryoEBUS) have been described to improve the diagnostic usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The literature suggests that this novel procedure could be associated with greater diagnostic usefulness than conventional EBUS-TBNA. METHODS: To develop a systematic analysis and meta-analysis on the diagnostic diagnostic yield and safety of cryobiopsy of hilar and mediastinal adenopathies compared to EBUS-TBNA. RESULTS: Seven studies that had included a total of 555 patients were considered in this review, with 365 (65.7%) of these patients having an etiology of malignant lymph node involvement. The overall diagnostic usefulness of cryoEBUS was higher compared to EBUS-TBNA (92% vs. 80%). However, when the results were analysed according to the specific aetiologies of the adenopathies, cryoEBUS was especially useful in cases of lymphomas or non-pulmonary carcinomas (83% vs. 42%) and in cases that were benign (87% vs. 60.1%), with no significant differences being found in specific cases of lung cancer. For lymphoma, cryoEBUS was diagnostic in 87% of cases compared to 12% for EBUS-TBNA and in addition, also allowed the characterisation of every lymphoma subtype. Genetic studies and immunohistochemical determination of PD-L1 was possible in almost all (97%) of the samples obtained by cryoEBUS, while this was only possible in 79% of those obtained by EBUS-TBNA. The most frequent complication was light bleeding, which was described in up to 85% of cases in some series. CONCLUSION: CryoEBUS could represent a promising technique in the diagnostic algorithm used for mediastinal and hilar involvement. Although cryoEBUS did not significantly improve the diagnosis of lung cancer compared to EBUS-TBNA, the results were significantly better in patients with benign pathologies and other tumour types, including lymphomas. In addition, it seems that the samples obtained by cryoEBUS better defined the histological subtypes of lymphoma and allowed complete molecular characterisation in cases of lung cancer. The technique has proven to be safe and no serious complications were described after the procedure.

High Levels of IL-1ß, TNF-α and MIP-1α One Month after the Onset of the Acute SARS-CoV-2 Infection, Predictors of Post COVID-19 in Hospitalized Patients.

The pandemic caused by SARS-CoV-2 infection has left behind a new symptomatology called post COVID-19, or "long COVID". The pathophysiological mechanisms still remain controversial; however, a link between persistent inflammation and these sequelae has been suggested. Herein, we longitudinally assessed up- and downstream molecules of the NLRP3 inflammasome's pathway in three study groups: healthy donors (HC, n = 14) and donors with a confirmed SARS-CoV-2 infection who had been hospitalized, the latter divided into post COVID-19 (PC, n = 27) and non-post COVID-19 patients (nPC, n = 27) based on the presence or absence of symptomatology at month 6, respectively. Plasma cytokines (IL-1ß, IL-3, IL-6, IL-8, IL-18, IP-10, MIG, TNF-α, IFN-γ, MIP-1α and MIP-1ß) and total peroxide (TPX) levels were quantified at baseline and at months 1 and 6 after the onset of the infection. Baseline values were the highest for both TPX and cytokines that progressively decreased thereafter the acute infection. IL-1ß, MIP-1α and TNF-α at month 1 were the only cytokines that showed a significant difference between nPC and PC. These findings suggest that a persistent inflammatory state one month after the onset of SARS-CoV-2 infection related to specific cytokines (IL-1ß, MIP-1α, and TNF-α) might guide to predicting post COVID-19 symptomatology.

Intramural hematoma of the pulmonary artery and hemopneumomediastinum after endobronchial ultrasound-guided transbronchial needle aspiration.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and effective technique for the sampling of mediastinal and hilar adenopathies. We describe the first reported case of pulmonary artery intramural hematoma after EBUS-TBNA puncture of this artery. The complication was visualized by ultrasound and resolved spontaneously.

Biological Biomarkers in Respiratory Diseases. / Biomarcadores biológicos en las enfermedades respiratorias.

In recent years, personalized or precision medicine has made effective inroads into the management of diseases, including respiratory diseases. The route to implementing this approach must invariably start with the identification and validation of biological biomarkers that are closely related to the diagnosis, treatment, and prognosis of respiratory patients. In this respect, biological biomarkers of greater or lesser reliability have been identified for most respiratory diseases and disease classes, and a large number of studies are being conducted in the search for new indicators. The aim of this review is to update the reader and to analyze the existing scientific literature on the existence and diagnostic, therapeutic, and prognostic validity of the most important biological biomarkers in the main respiratory diseases, and to identify future challenges in this area.

Different Faces of Idiopathic Pulmonary Fibrosis With Preserved Forced Vital Capacity.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials. METHODS: Spanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed. RESULTS: 225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO <60% and consistent UIP radiological pattern. CONCLUSIONS: Patients with preserved FVC but presenting UIP radiological pattern and moderate-severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.

Mediastinal staging for non-small cell lung cancer.

The staging of mediastinal lymph nodes for lung cancer is crucial for planning treatments or reinterventions. In potentially curable patients the aim of mediastinal staging is to exclude the presence of malignancy in mediastinal lymph nodes with a high level of accuracy while also considering clinical factors and the balance of the benefits and risks of tissue sampling techniques. Mediastinal staging is based on computed tomography (CT) and positron emission tomography (PET) and can be sufficient when no mediastinal abnormalities are present and the probability of unforeseen N2 disease is low. In the case of bulky lymph nodes with a high probability of malignancy in PET-CT, tissue confirmation is not normally required. If mediastinal sampling is needed it can be achieved by endosonographic techniques, including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) or a combination of the two. Positive results do not need further confirmation. In the case of negative results, surgical techniques still play a role in the selected cases discussed by multidisciplinary lung cancer committees. New mediastinal surgical techniques including video-assisted cervical mediastinoscopy (VACM), video-assisted mediastinoscopic lymphadenectomy (VAMLA), and transcervical extended mediastinal lymphadenectomy (TEMLA) have been shown to be useful in selected patients. Final pathological staging is based on lymph node removal during surgery and can be achieved by taking one of two approaches: lymph node sampling or systematic lymph node sampling. The accuracy of PET-CT and mediastinal endosonography is lower for mediastinal restaging than it is for surgical techniques; their false positive and false negative (FN) rate is high and so, they require histological confirmation. Here we explain and revise the results from the most recent studies and current international guidelines.

Cost Effectiveness of Malignant Pleural Effusion with Indwelling Catheter: Systematic Review.

Background: The current cost of treatment of malignant pleural effusion (MPE) with an indwelling pleural catheter (IPC) is unclear. Objective: We propose a review of the scientific evidence on the cost and effectiveness of this therapeutic option. Methods: Systematic review of the literature on the cost and effectiveness of the treatment of MPE by IPC, according to the PRISMA methodology and quality according to the scientific guidelines. Results: A total of 4 articles, 152 patients, and 159 IPCs were included. The use of IPC was associated with improvement in symptoms and quality of life. The most common complications were infections (empyema in 20.9% of patients and cellulitis in 17.3%); 9% of cases were hospitalized due to complications, and <2% required subsequent procedures. The average cost of IPC (set/drainage bottles) ranged from €2,025.6 to €1,200.5 if it was placed on an outpatient basis, €1,100 if survival was <6 weeks, and €4,028 in patients with mesothelioma. Complications increased the cost, and taking into account follow-up visits, additional tests, and days of admission for complications, the cost was >€5,000. Compared with pleurodesis, the cost of IPC was significantly lower when patient survival was <14 weeks, but not when survival was longer or home care was required. Conclusions: The use of IPC is associated with good control of MPE and seldom requires many subsequent procedures; however, it is also associated with a certain rate of complications, which may increase costs. However, ambulatory management may help reduce costs, which are directly related to the type of tumor, the duration of survival, and the need for specialized treatment.

Multivariate study of predictive factors for clearly defined lung lesions without visible endobronchial lesions in transbronchial biopsy.

BACKGROUND: Although the diagnostic validity and predictive factors for the diagnostic yield of transbronchial biopsy (TBB) of clearly defined pulmonary lesions with no visible endobronchial lesion have been analyzed in numerous studies, very few have used multivariate analysis techniques to evaluate the validity of TBB as a diagnostic tool or to analyze the independent influence of clearly dependent variables, such as the bronchus sign and lesion size. METHODS: We retrospectively analyzed all cases in which this type of lesion underwent TBB under fluoroscopic control between 2006 and 2008. The analyzed variables included lesion size, localization, the presence of the bronchus sign, and the final result obtained. We performed a descriptive analysis of the TBB results and a multivariate analysis of the predictive factors for the results using logistic regression techniques. RESULTS: A total of 273 patients (206 males, 75.5%) were included in the study. The average lesion diameter was 34 (± 16) mm, with 24% 2 cm or smaller. Twenty-eight percent of the lesions were localized in the lower lobes and 32% in the peripheral third of the lung. The bronchus sign was present in 28% of the patients. Seventy-eight percent of the patients had primary or metastatic malignant lung lesions, the rest were benign lesions of diverse etiology. TBB was diagnostic in 45.4% of cases. In the multivariate analysis, the only independent predictors of outcome were malignant etiology (OR = 4.8; 95% CI = 2.210.4), diameter >20 mm (OR = 3.6; 95% CI = 1.8-7.3), and the presence of the bronchus sign (OR = 2.4; 95% CI = 1.3-4.3). CONCLUSIONS: TBB of lesions clearly delimited without an endobronchial lesion can lead to diagnosis in almost half of the patients. The nature of the lesion, diameter >20 mm, and the presence of the bronchus sign are independent predictors of outcome.