Virginia Leiro-Fernández

The Endobronchial Ultrasound-Guided Transbronchial Needle Biopsy Learning Curve for Mediastinal and Hilar Lymph Node Diagnosis

The learning curve required for the endobronchial ultrasoundguided transbronchial needle biopsy (EBUS-TBNA) of mediastinal or hilar lymph nodes is unclear, and the evidence is scarce and contradictory. 1 4 Two of the evidentiary studies 2 , 3 only analyzed the learning curve of EBUS-TBNA for lung cancer diagnosis and staging and did not include the use of this technique in the study of lymph nodes affected by other pathologies. Other factors that might be infl uenced by learning have also not been examined. 2 4 To address these issues, we conducted a prospective study to describe the learning curve of an experienced bronchoscopy team in a unselected sample of patients with mediastinal or hilar lymph nodes. Team performance was analyzed not only in terms of the diagnostic yield of the procedure, but also to evaluate procedure length, number of lymph node passes performed to obtain adequate samples, and number of lymph nodes studied per patient. We included unselected consecutive patients with mediastinal or hilar lymph node . 10 mm in the short axis on CT scan or . 5 mm in the presence of PET scan-positive uptake. The study involved a team of two bronchoscopists with . 10 years experience in diagnostic bronchoscopy, including conventional transbronchial needle biopsy. The bronchoscopists had previously conducted extensive theoretical training and several practical workshops and performed between fi ve and 10 supervised procedures. The learning curve was evaluated by analyzing consecutive groups of 20 patients, the number of adequate samples obtained, and the diagnostic accuracy of the procedure. We also recorded the other variables shown in Table 1 . Over a period of 13 months, EBUS-TBNA was performed for 215 lymph nodes in 120 patients (71 with lung cancer, 16 with extrapulmonary carcinomas, seven with lymphomas, and 26 with several nonmalignant pathologies). Table 1 shows these values in groups of 20 consecutive patients. No serious complications were reported. The present study demonstrated that the diagnostic effectiveness of EBUS-TBNA clearly improved with an increasing number of procedures performed, allowing for access to a greater number of lymph nodes without increasing the length of the procedure by reducing the number of punctures in each nodal station. Analyzing the studies included in systematic reviews and published meta-analyses, 5 , 6 the diagnostic accuracy of EBUS-TBNA is between 85% and 98%. Accordingly, and based on our fi ndings, we could argue that the minimal diagnostic yield is achieved with procedure 60 but can be improved and even reach optimal results after 100 patients. We hope that this study and others in the same line help scientifi c societies to establish specifi c recommendations for learning linear EBUS-TBNA. 1 , 7

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. Residential radon exposure increases risk of lung cancer in never-smokers, ETS exposure may raise radon effect http://ow.ly/xRVte For editorial comments see page 850.

N-acetyltransferase 2 polymorphisms and risk of anti-tuberculosis drug-induced hepatotoxicity in Caucasians.

OBJECTIVE To analyse slow-acetylation N-acetyltransferase 2 (NAT2) polymorphisms for their association with the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH). DESIGN A case-control study including Caucasian patients with tuberculosis (TB) treated with isoniazid, rifampicin and pyrazinamide. NAT2 genotype results were compared between ATDH cases and controls and with a healthy Spanish control population of Caucasian origin. RESULTS Fifty cases and 67 controls were included in the study. Slow, intermediate and rapid NAT2 genotypes were found in respectively 72%, 18% and 10% of cases compared with 65.7%, 25.4% and 9% of controls (P> 0.05). On comparing NAT2 genotypes among cases with those among healthy controls (n = 1312), we found more slow NAT2 genotypes and fewer intermediate genotypes among cases (respectively 72% and 18% in cases vs. 54.8% and 38.1% in controls; OR 2.07, 95%CI 1.12-2.79, P = 0.016 and OR 0.37, 95%CI 0.18-0.75, P = 0.003). CONCLUSIONS We could not demonstrate an increased risk of ATDH related to the presence of slow NAT2 polymorphisms among this Caucasian TB cohort. However, we found a significantly greater frequency of slow and a significantly lower frequency of intermediate NAT2 genotypes among the ATDH cases compared with the healthy control population.

Efectividad a corto y largo plazo de un programa tutelado de formación en espirometrías para profesionales de atención primaria

INTRODUCTION Despite the importance of spirometry, its use and quality are limited in the Primary Care setting. There are few accredited training programs that have demonstrated improvement in the quality of spirometric studies. In this paper, we analyze the short- and long-term effectiveness of a supervised training program for performing and interpreting spirometries. METHODOLOGY Ours is an intervention study with before and after measurements. The target population included teams of physicians and nursing staff at 26 health-care centers in the area of Vigo (Galicia, Spain). The structured training program involved 2 theoretical and practical training sessions (that were 2months apart), an intermediate period of 30 supervised spirometries performed in the respective centers and weekly e-mail exercises. Effectiveness was evaluated using exercises at the beginning (test 1) and the end (test 2) of the 1st day, 2nd day (test 3) and one year later (test 4), as well as the analysis of spirometries done in month1, month2 and one year later. Participants also completed a survey about their satisfaction. RESULTS 74 participants initiated the program; 72 completed the program, but only 45 participated in the one-year evaluation. Mean test scores were: 4.1±1.9 on test 1; 7.5±1.6 on test 2; 8.9±1.3 on test 3, and 8.8±1.4 on test 4. During month1, the percentage of correctly done/interpreted tests was 71%, in month two it was 91% and after one year it was 83% (P<.05). CONCLUSIONS A training program based on theoretical and practical workshops and a supervised follow-up of spirometries significantly improved the ability of Primary Care professionals to carry out and interpret spirometric testing, although the quality of the tests diminished over time.

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.

Exposición a radón residencial y cáncer de pulmón en nunca fumadores. Resultados preliminares del estudio LCRINS

INTRODUCTION AND OBJECTIVE Residential radon is the second most important risk factor for lung cancer and the first among never-smokers. The objective of this study is to report the concentrations of residential radon in a series of never-smoker cases recruited in a multicenter study of cases and controls in northwestern Spain. In this study, all the hospitals in the Spanish province of Galicia and one from Asturias participated. PATIENTS AND METHODS The present article includes a series of cases with residential radon measurements. All the subjects were personally interviewed, 3 ml of blood were taken from each, and they were each given instructions about how to place a residential radon detector in their homes. RESULTS Sixty-nine case subjects were recruited, 84% of whom were women with a mean age of 71, and 81% of whom had adenocarcinoma. The average concentration of residential radon in the cases was 237 Bq/m(3), while the average concentration in the Galician population is 79 Bq/m(3). No relationship was observed between the concentration of residential radon and either sex or age at the time of diagnosis of the cases, but there was a tendency towards having a greater concentration in those diagnosed with small-cell and large-cell carcinoma. CONCLUSIONS The concentrations of residential radon in the cases included are very high at about three times the average concentration of residential radon to which the general population of Galicia is exposed.

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. Residential radon might cause genetic alterations in driver genes for lung cancer in never-smokers http://ow.ly/1u4P302JdBs

Thoracic Ultrasound-Assisted Selection for Pleural Biopsy With Abrams Needle

BACKGROUND: Closed pleural biopsy (CPB) in patients with malignant pleural effusion is less sensitive than cytology. Ultrasound-assisted CPB allows biopsies to be performed in the lower thoracic parietal pleura, where secondary spread from pleural metastases is initially more likely to be found. We analyzed whether choosing the point of entry for CPB with thoracic ultrasound assistance influences the diagnostic yield in malignant pleural effusion. METHODS: This prospective study included patients who underwent CPB performed by an experienced pulmonologist in 2008–2010 (group A) and thoracic ultrasound was used to select the biopsy site. The results were compared with a historical series of CPB performed by the same pulmonologist without the assistance of thoracic ultrasound (group B). An Abrams needle was used in all cases. We analyzed the obtaining of pleural tissue and the diagnostic yield. RESULTS: We included 114 CPBs from group A (23% tuberculous pleural effusion, 27% malignant pleural effusion) and 67 CPBs from group B (24% tuberculous pleural effusion, 30% malignant pleural effusion) (P = .70). Pleural tissue was obtained in 96.5% of the group A CPBs and 89.6% of the group B CPBs (P = .05). The diagnostic yields of CPB for tuberculous pleural effusion and malignant pleural effusion in group A were 89.5% and 77.4%, respectively, and 91.7% and 60%, respectively, in group B (P = .80 for tuberculous pleural effusion, and P = .18 for malignant pleural effusion). CONCLUSIONS: Selecting the point of entry for CPB using thoracic ultrasound increases the likelihood of obtaining pleural tissue and the diagnostic yield, but without statistical significance. We recommend ultrasound-assisted CPB to investigate pleural effusion, since the diagnostic yield of a pleural biopsy with an Abrams needle increased by > 17% in subjects with malignant pleural effusion.

Prognostic value of aberrant hypermethylation in pleural effusion of lung adenocarcinoma

Lung adenocarcinoma is one of the most frequent causes of malignant pleural effusions (MPE). The presence of MPE bears a poor prognosis. Although epigenetic changes are commonly related to human neoplasia, scarce date is available on patients with MPE. We aimed to estimate the prognostic value of DNA methylation of tumor suppressor genes from pleural fluid. Thirty patients with MPE due to lung adenocarcinoma were prospectively included. Methylation-specific (MS) PCR was used to study the methylation status of the promoter region of tumor suppressor genes p16/INK4a, MGMT, BRCA1 and RARβ in pleural fluid. Clinical data and survival were collected. Survival analysis was performed using Kaplan-Meier plots and Cox regression. Hypermethylation in at least one gene was detected in 25 patients (83.3%). On multivariate analysis factors significantly associated with shorter survival were the lack of hypermethylation in any of the studied genes (hazard ratio = 9.3; p = 0.001), Charlson index ≥ 3 (hazard ratio = 9.6, p = 0.002) and no oncological treatment (hazard ratio = 11.1; p < 0.001). Analysis of aberrant promoter hypermethylation of tumor suppressor genes may be useful in predicting prognosis, but further studies are needed to validate our findings.

Residential radon and lung cancer characteristics in never smokers

Abstract Purpose: The aim of this study is to assess if there is a relationship between residential radon and lung cancer histological types and patients’ age at diagnosis. Materials and methods: We conducted a multicenter hospital-based case-control study with eight participating hospitals. We included 216 never-smoking cases with primary lung cancer and 329 never-smoking controls. Controls were frequency matched with cases on age and sex distribution. Of them, 198 cases (91.7%) and 275 controls (83.5%) had residential radon measurements. Results: Lung cancer risk reached statistical significance only for adenocarcinoma (Odds ratio [OR] 2.19; 95% Confidence interval [CI] 1.44–3.33), for other histologies the results were marginally significant. Residential radon level was higher for patients diagnosed before 50 and 60 years old than for older lung cancer cases. Conclusions: Residential radon in never smokers seems to be a risk factor for all lung cancer histologies. Individuals diagnosed at a younger age have a higher residential radon concentration, suggesting an accumulative effect on lung cancer appearance.