ABSTRACT
About 4% to 7% of the non-small-cell lung cancer patients have anaplastic lymphoma kinase (ALK) rearrangements, and specific targeted therapies improve patients' outcomes significantly. ALK gene fusions are detected by immunohistochemistry or fluorescent in situ hybridization as gold standards in South America. Next-generation sequencing-based assays are a reliable alternative, able to perform simultaneous detection of multiple events from a single sample. We analyzed 4240 non-small-cell lung cancer samples collected in 37 hospitals from Chile, Brazil, and Peru, where ALK rearrangements were determined as part of their standard of care (SofC) using either immunohistochemistry or fluorescent in situ hybridization. A subset of 1450 samples was sequenced with the Oncomine Focus Assay (OFA), and the concordance with the SofC tests was measured. An orthogonal analysis was performed using a real-time quantitative PCR echinoderm microtubule-associated protein-like 4-ALK fusion detection kit. ALK fusion prevalence is similar for Chile (3.67%; N = 2142), Brazil (4.05%; N = 1013), and Peru (4.59%; N = 675). Although a comparison between OFA and SofC assays showed similar sensitivity, OFA had significantly higher specificity and higher positive predictive value, which opens new opportunities for a more specific determination of ALK gene rearrangements.
Subject(s)
Anaplastic Lymphoma Kinase/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Gene Fusion , High-Throughput Nucleotide Sequencing/methods , Lung Neoplasms/genetics , Oncogene Proteins, Fusion/genetics , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Carcinoma, Non-Small-Cell Lung/epidemiology , Chile/epidemiology , Female , Gene Rearrangement , Humans , Immunohistochemistry/methods , In Situ Hybridization, Fluorescence/methods , Lung Neoplasms/epidemiology , Male , Middle Aged , Peru/epidemiology , Prospective Studies , Retrospective Studies , Standard of Care , Young AdultABSTRACT
Molecular testing for genomic variants is recommended in advanced non-small cell lung cancer (NSCLC). Standard tissue biopsy is sometimes infeasible, procedurally risky, or insufficient in tumor tissue quantity. We present the analytical validation and concordance study of EGFR variants using a new 17-gene liquid biopsy assay (NCT02762877). Of 144 patients enrolled with newly diagnosed or progressive stage IV nonsquamous NSCLC, 140 (97%) had liquid assay results, and 117 (81%) had both EGFR blood and tissue results. Alterations were detected in 58% of liquid samples. Overall tissue-liquid concordance for EGFR alterations was 94.0% (95% CI 88.1%, 97.6%) with positive percent agreement of 76.7% (57.7%, 90.1%) and negative percent agreement of 100% (95.8%, 100%). Concordance for ALK structural variants was 95.7% (90.1%, 98.6%). This assay detected alterations in other therapeutically relevant genes at a rate similar to tissue analysis. These results demonstrate the analytical and clinical validity of this 17-gene assay.
ABSTRACT
Lipoid pneumonia is an unusual cause of aspiration pneumonia with diverse radiologic manifestations. One of these are pulmonary nodules in which the main differential diagnosis is pulmonary carcinoma. We report an 85 years old male, an 85 years old female and a 34 years old male in whom percutaneous biopsies of suspicious nodules were compatible with lipoid pneumonia.
Subject(s)
Humans , Male , Female , Adult , Aged, 80 and over , Pneumonia, Lipid/diagnostic imaging , Pneumonia, Lipid/pathology , Biopsy , Tomography, X-Ray ComputedABSTRACT
Lipoid pneumonia is an unusual cause of aspiration pneumonia with diverse radiologic manifestations. One of these are pulmonary nodules in which the main differential diagnosis is pulmonary carcinoma. We report an 85 years old male, an 85 years old female and a 34 years old male in whom percutaneous biopsies of suspicious nodules were compatible with lipoid pneumonia.
Subject(s)
Pneumonia, Lipid/diagnostic imaging , Adult , Aged, 80 and over , Biopsy , Female , Humans , Male , Pneumonia, Lipid/pathology , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Bronchoscopy is a minimally invasive procedure used for the diagnosis of lung cancer. AIM: To report our experience with bronchoscopy and transbronchial biopsies for the diagnosis of potentially malignant pulmonary lesions. MATERIAL AND METHODS: Revision of electronic records from patients who underwent transbronchial biopsies seeking for lung cancer. The diagnostic yield of the procedure was evaluated using pathology reports or a 24 months follow up. RESULTS: 261 patients were included. Bronchoscopy was diagnostic in 65% of cases. Lesions mean diameter was 51 mm (range 9-120 mm). Diagnostic yield for lesions less than 30 mm was 59%, for lesions less than 35 mm was 61%, and for lesions over 40 mm was 69%. The presence of malignant lesions and their location in the superior or middle lobe were associated with a better predictive value of the procedure. TNM staging was IIIB/IV in 80% of the patient at the time of diagnosis. CONCLUSIONS: The diagnostic yield of bronchoscopy is influenced by the etiology and location of lung lesions.
Subject(s)
Adenocarcinoma/pathology , Bronchoscopy/methods , Carcinoma, Squamous Cell/pathology , Lung Neoplasms/pathology , Lung/pathology , Adenocarcinoma/secondary , Aged , Anesthesia, Local , Biopsy/methods , Biopsy, Needle , Carcinoma, Squamous Cell/secondary , Cohort Studies , Female , Fluoroscopy/methods , Follow-Up Studies , Humans , Lung Neoplasms/secondary , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Smoking/pathologyABSTRACT
Background: Bronchoscopy is a minimally invasive procedure used for the diagnosis of lung cancer. Aim: To report our experience with bronchoscopy and transbronchial biopsies for the diagnosis of potentially malignant pulmonary lesions. Material and Methods: Revision of electronic records from patients who underwent transbronchial biopsies seeking for lung cancer. The diagnostic yield of the procedure was evaluated using pathology reports or a 24 months follow up. Results: 261 patients were included. Bronchoscopy was diagnostic in 65% of cases. Lesions mean diameter was 51 mm (range 9-120 mm). Diagnostic yield for lesions less than 30 mm was 59%, for lesions less than 35 mm was 61%, and for lesions over 40 mm was 69%. The presence of malignant lesions and their location in the superior or middle lobe were associated with a better predictive value of the procedure. TNM staging was IIIB/IV in 80% of the patient at the time of diagnosis. Conclusions: The diagnostic yield of bronchoscopy is influenced by the etiology and location of lung lesions.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma/pathology , Bronchoscopy/methods , Carcinoma, Squamous Cell/pathology , Lung Neoplasms/pathology , Lung/pathology , Adenocarcinoma/secondary , Anesthesia, Local , Biopsy, Needle , Biopsy/methods , Carcinoma, Squamous Cell/secondary , Cohort Studies , Fluoroscopy/methods , Follow-Up Studies , Lung Neoplasms/secondary , Neoplasm Staging , Predictive Value of Tests , Smoking/pathologyABSTRACT
BACKGROUND: Flexible bronchoscopy is a useful diagnostic tool with a relative low rate of complications. AIM: To analyze post procedure risk of complications after flexible bronchoscopy with transbronchial or bronchial biopsy. MATERIAL AND METHODS: The electronic database of a bronchoscopy unit at a general Hospital was analyzed. All procedures performed between 2009 and 2011 were reviewed and complications recorded. The primary outcome measure was the risk for complications defined as the percentage of procedures complicated by hemorrhage, pneumothorax, desaturation < 80% and other complications. We used a logistic regression model to explore the association between each procedure characteristic and complication. RESULTS: One thousand seventy nine procedures were included in the analysis. Eight percent had complications. Among these, the frequency of hemorrhage was 5.9% and pneumothorax was 0.3%. Factors associated with complications were exclusive use of topical anesthesia with an odds ratio (OR) of 1.72 (confidence intervals (CI): 1.04-2.86), regular or bad intolerance to the procedure with an OR 4.70 (CI: 3.00-7.38) and performing biopsies of the upper lobes with an OR of 1.76 (CI: 1.04-2.97). CONCLUSIONS: Exclusive use of topical anesthesia, performing biopsies of the upper lobes and procedure tolerance were risk factors associated with complications following bronchoscopic biopsies.
Subject(s)
Bronchoscopy/adverse effects , Bronchoscopy/statistics & numerical data , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
INTRODUCTION: The population of immunocompromised patients has increased in recent decades. Many of these patients eventually present infectious complications including pneumonia, which is a diagnostic that must to be prompt and accurate. OBJECTIVE: To review the basis of the diagnosis of pneumonia in the immunocompromised patient. Sorted by the methodology of Bayesian inference, very relevant in the diagnostic attribution, we review the main basis of the diagnosis of pneumonia of immunocompromised patients: the epidemiology, the clinical history including the type of immunosuppression that weigh the likelihood of attribution a priori of an etiologic agent, and finally, the findings in the image (or likelihood function). CONCLUSION: Although in general the findings are not pathognomonic and there is much overlap in the images, there are several features that orient in one direction or another. Proper assessment of the prior probability and the likelihood function is allowing ultimately a good diagnostic proposition.
Subject(s)
Immunocompromised Host/immunology , Pneumonia/microbiology , Bayes Theorem , Female , Humans , Likelihood Functions , Male , Pneumonia/diagnostic imaging , Pneumonia/immunology , RadiographyABSTRACT
Introduction: The population of immunocompromised patients has increased in recent decades. Many of these patients eventually present infectious complications including pneumonia, which is a diagnostic that must to be prompt and accurate. Objective: To review the basis of the diagnosis of pneumonia in the immunocompromised patient. Sorted by the methodology of Bayesian inference, very relevant in the diagnostic attribution, we review the main basis of the diagnosis of pneumonia of immunocompromised patients: the epidemiology, the clinical history including the type of immunosuppression that weigh the likelihood of attribution a priori of an etiologic agent, and finally, the findings in the image (or likelihood function). Conclusion: Although in general the findings are not pathognomonic and there is much overlap in the images, there are several features that orient in one direction or another. Proper assessment of the prior probability and the likelihood function is allowing ultimately a good diagnostic proposition.
Introducción: La población de pacientes inmunocomprometidos se ha incrementado en las últimas décadas. Gran parte de estos pacientes presenta en algún momento complicaciones infecciosas, entre ellas la neumonía, lo que constituye un desafío diagnóstico que debe ser rápido y acertado. Objetivo: Revisar las bases del diagnóstico de las neumonías del paciente inmunocomprometido. Ordenados por la metodología de la inferencia Bayesiana, muy relevante en la atribución diagnóstica, destacamos y revisamos los pilares fundamentales en el diagnóstico de las neumonías del inmunocomprometido: la epidemiología, los antecedentes clínicos incluyendo el tipo de inmunodepresión, que pesan en la probabilidad de atribución a priori de un agente etiológico, y finalmente, los hallazgos en la imagen (o función de verosimilitud). Conclusión: Los hallazgos de imagen que, aunque en general no son patognomónicos y existe mucha superposición, presentan algunas características que orientan en una u otra dirección. La adecuada valoración de la probabilidad a priori y la función de verosimilitud son las que permiten en definitiva una buena proposición diagnóstica.
Subject(s)
Female , Humans , Male , Immunocompromised Host/immunology , Pneumonia/microbiology , Bayes Theorem , Likelihood Functions , Pneumonia/immunology , PneumoniaABSTRACT
Background: Flexible bronchoscopy is a useful diagnostic tool with a relative low rate of complications. Aim: To analyze post procedure risk of complications after flexible bronchoscopy with transbronchial or bronchial biopsy. Material and Methods: The electronic database of a bronchoscopy unit at a general Hospital was analyzed. All procedures performed between 2009 and 2011 were reviewed and complications recorded. The primary outcome measure was the risk for complications de fined as the percentage of procedures complicated by hemorrhage, pneumothorax, desaturation < 80% and other complications. We used a logistic regression model to explore the association between each procedure characteristic and complication. Results: One thousand seventy nine procedures were included in the analysis. Eight percent had complications. Among these, the frequency of hemorrhage was 5.9% and pneumothorax was 0.3%. Factors associated with complications were exclusive use of topical anesthesia with an odds ratio (OR) of 1.72 (confidence intervals (CI): 1.04-2.86), regular or bad intolerance to the procedure with an OR 4.70 (CI: 3.00-7.38) and performing biopsies of the upper lobes with an OR of 1.76 (CI: 1.04-2.97). Conclusions: Exclusive use of topical anesthesia, performing biopsies of the upper lobes and procedure tolerance were risk factors associated with complications following bronchoscopic biopsies.
Subject(s)
Female , Humans , Male , Middle Aged , Bronchoscopy/adverse effects , Bronchoscopy/statistics & numerical data , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Pulmonary diseases are common among HIV infected patients. The prevalence of the different diseases varies greatly. AIM: To identify the different pulmonary diseases that affect a Chilean population of HIV infected patients and to identify factors associated with in hospital mortality. MATERIAL AND METHODS: Retrospective review of the clinical records of all HIV infected patients with lung diseases discharged from our institution during a period of 3.5 years. Collection of demographic and biomedical data. RESULTS: One hundred seventy one patients (aged 35.7 years, 86% men) had 236 episodes of lung diseases. Only 13.5% of the patients were receiving antiretroviral therapy and 18% were on pneumocystis prophylaxis. Infectious diseases accounted for 87% of the discharges, neoplasm for 5.1%. Pneumocystis jirovecii infection was responsible for 37.7% of the episodes, community acquired pneumonia was seen in 24.1% and mycobacterial diseases in 14.4%. Two or more conditions were present in 13.6%. Death during hospital stay occurred in 19.5%. Multivariate analysis identified pneumothorax as the only significant independent predictor of in-hospital mortality in patients with pneumocystis pneumonia, while nosocomial pneumonia was the only predictor of death among patients with non-pneumocystis pulmonary diseases. CONCLUSIONS: Infectious diseases were the main cause of hospitalization among Chilean HIV infected patients. Mortality among these patients remains high. Appropriate antiretroviral therapy and prophylaxis may alter pulmonary disease prevalence in the future. Every effort should be made to avoid the development of pneumothorax and nosocomial pneumonia.
