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BACKGROUND: Benign airway stenosis (BAS) represents a significant burden on patients, providers, and healthcare systems. Spray cryotherapy (SCT) has been proposed as an adjunctive treatment to reduce BAS recurrence. We sought to examine safety and practice variations of the latest SCT system when used for BAS. METHODS: We conducted a retrospective multicenter cohort study in seven academic institutions within the Interventional Pulmonary Outcomes Group. All patients who underwent at least one SCT session with a diagnosis of BAS at the time of procedure at these institutions were included. Demographics, procedure characteristics, and adverse events were captured through each center's procedural database and electronic health record. RESULTS: A total of 102 patients underwent 165 procedures involving SCT from 2013 to 2022. The most frequent etiology of BAS was iatrogenic (n = 36, 35%). In most cases, SCT was used prior to other standard BAS interventions (n = 125; 75%). The most frequent SCT actuation time per cycle was five seconds. Pneumothorax complicated four procedures, requiring tube thoracostomy in two. Significant post-SCT hypoxemia was noted in one case, with recovery by case conclusion and no long-term effects. There were no instances of air embolism, hemodynamic compromise, or procedural or in-hospital mortality. CONCLUSION: SCT as an adjunctive treatment for BAS was associated with a low rate of complications in this retrospective multicenter cohort study. SCT-related procedural aspects varied widely in examined cases, including actuation duration, number of actuations, and timing of actuations relative to other interventions.
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Criocirugía , Crioterapia , Humanos , Estudios Retrospectivos , Estudios de Cohortes , Constricción Patológica/etiología , Crioterapia/efectos adversos , Criocirugía/efectos adversosRESUMEN
BACKGROUND: Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy (PDT) delivered via navigational bronchoscopy is feasible and safe for ablation of peripheral lung tumors. METHODS: Two studies evaluated PDT in patients with solid peripheral lung tumors followed by clinical follow-up (nonresection study, N=5) or lobectomy (resection study, N=10). Porfimer sodium injection was administered 40 to 50 hours before navigational bronchoscopy. Lesion location was confirmed by radial probe endobronchial ultrasonography. An optical fiber diffuser was placed within or adjacent to the tumor under fluoroscopic guidance; laser light (630 nm wavelength) was applied at 200 J/cm of diffuser length for 500 seconds. Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors at 3 and 6 months postprocedure (nonresection study) and pathologically (resection study). RESULTS: There were no deaths, discontinuations for adverse events, or serious or grade ≥3 adverse events related to study treatments. Photosensitivity reactions occurred in 8 of 15 patients: 6 mild, 1 moderate, 1 severe (elevated porphyrins noted in blood after treatment). Among 5 patients with clinical follow-up, 1 had complete response, 3 had stable disease, and 1 had progressive disease at 6 months follow-up. Among 10 patients who underwent lobectomy, 1 had no evidence of tumor at resection (complete response), 3 had 40% to 50% tumor cell necrosis, 2 had 20% to 35%, and 4 had 5% to 10%. CONCLUSION: PDT for nonthermal ablation of peripheral lung tumors was feasible and safe in this small study. Further study is warranted to evaluate efficacy and corroborate the safety profile.
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Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Fotoquimioterapia/efectos adversos , Estudios de Factibilidad , Éter de Dihematoporfirina/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Luz , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
Background: Current medical society guidelines recommend a procedural number for obtaining electromagnetic navigational bronchoscopy (ENB) competency and for institutional volume for training. Objective: To assess learning curves and estimate the number of ENB procedures for interventional pulmonology (IP) fellows to reach competency. Methods: We conducted a prospective multicenter study of IP fellows in the United States learning ENB. A tool previously validated in a similar population was used to assess IP fellows by their local faculty and two blinded independent reviewers using virtual recording of the procedure. Competency was determined by performing three consecutive procedures with a competency score on the assessment tool. Procedural time, faculty global rating scale, and periprocedural complications were also recorded. Results: A total of 184 ENB procedures were available for review with assessment of 26 IP fellows at 16 medical centers. There was a high correlation between the two blinded independent observers (rho = 0.8776). There was substantial agreement for determination of procedural competency between the faculty assessment and blinded reviewers (kappa = 0.7074; confidence interval, 0.5667-0.8482). The number of procedures for reaching competency for ENB bronchoscopy was determined (median, 4; mean, 5; standard deviation, 3.83). There was a wide variation in the number of procedures to reach competency, ranging from 2 to 15 procedures. There were six periprocedural complications reported, four (one pneumomediastinum, three pneumothorax) of which occurred before reaching competence and two pneumothoraces after achieving competence. Conclusion: There is a wide variation in acquiring competency for ENB among IP fellows. Virtual competency assessment has a potential role but needs further studies.
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The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.
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Detección Precoz del Cáncer , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Tamizaje MasivoRESUMEN
Photodynamic therapy (PDT) is an FDA approved treatment for lung cancer. In the United States the photosensitizer porfimer sodium (Photofrin®, Pinnacle Biologics) is intravenously introduced at 2mg/kg. After approximately 48 h, illumination to activate the photosensitizer is initiated, with 630nm red light at 200J/cm, delivered by fiber-optic catheter, brought to the tumor endo- bronchially, and delivered for 500 s. This will create, in the presence of oxygen, a Type II Photodynamic Reaction (PDR) which generates singlet oxygen species that are tumor ablative. Classically, PDT for lung cancer has been employed for symptomatic central and obstructing tumors with great success. This case report describes an innovative approach to treat a peripheral, early stage lung cancer employing magnetic navigation and endobronchial treatment. We report on a 79 year old male with numerous comorbidities including pulmonary fibrosis, who was found to have a biopsy proven peripheral and solitary non-small cell cancer. Due to prior SBRT (stereotactic body radiation therapy) with dose levels causing radiation fibrosis, he was not a candidate for repeat SBRT, and he was not a surgical candidate due to comorbidities. Tumor control with PDT was achieved without treatment related morbidity. This report details our findings.
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Neoplasias Pulmonares , Fotoquimioterapia , Anciano , Éter de Dihematoporfirina/uso terapéutico , Humanos , Pulmón/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
BACKGROUND: Bronchial thermoplasty is a device-based treatment for subjects ≥ 18 years of age with severe asthma poorly controlled with inhaled corticosteroids and long-acting beta-agonists. The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma (PAS2) study collected data on patients with severe asthma undergoing this procedure. RESEARCH QUESTION: What are the 5-year efficacy and safety results in patients with severe asthma who have undergone bronchial thermoplasty? STUDY DESIGN AND METHODS: This was a prospective, open-label, observational, multicenter study conducted in the United States and Canada. Subjects 18 to 65 years of age who were taking inhaled corticosteroids ≥ 1,000 µg/d (beclomethasone or equivalent) and long-acting beta-agonists ≥ 80 µg/d (salmeterol or equivalent) were included. Severe exacerbations, hospitalization, ED visits, and medication usage were evaluated for the 12 months prior to and at years 1 through 5 posttreatment. Spirometry was evaluated at baseline and at years 1 through 5 posttreatment. RESULTS: A total of 284 subjects were enrolled at 27 centers; 227 subjects (80%) completed 5 years of follow-up. By year 5 posttreatment, the proportion of subjects with severe exacerbations, ED visits, and hospitalizations was 42.7%, 7.9%, and 4.8%, respectively, compared with 77.8%, 29.4%, and 16.1% in the 12 months prior to treatment. The proportion of subjects on maintenance oral corticosteroids decreased from 19.4% at baseline to 9.7% at 5 years. Analyses of subgroups based on baseline clinical and biomarker characteristics revealed a statistically significant clinical improvement among all subgroups. INTERPRETATION: Five years after treatment, subjects experienced decreases in severe exacerbations, hospitalizations, ED visits, and corticosteroid exposure. All subgroups demonstrated clinically significant improvement, suggesting that bronchial thermoplasty improves asthma control in different asthma phenotypes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01350336; URL: www. CLINICALTRIALS: gov.
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Asma , Termoplastia Bronquial , Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Asma/cirugía , Termoplastia Bronquial/métodos , Humanos , Estudios Prospectivos , Calidad de VidaRESUMEN
BACKGROUND: The discovery that early diagnosis can reduce the mortality of lung cancer provides firm evidence that early surgical intervention is effective. However, surgical resection is available only to those who are healthy enough to tolerate the procedure. Vapor ablation may provide an additional method of treating the lung cancer patient, and has been studied in humans for emphysema treatment. In swine, we previously demonstrated that bronchoscopically delivered thermal vapor ablation (BTVA) could be accurately applied, was uniform, anatomically confined, and was tolerated by the animal. To provide evidence that BTVA may be a feasible method of treatment in humans, and since human and swine lungs have differing airway and segmental anatomy, we extended our studies to deceased human lungs to determine if anatomically confined and uniform ablations could be obtained with levels of energy comparable with our swine and human emphysema studies. METHODS: We obtained fresh, deceased human lungs and performed BTVA with increasing energy in subsegmental regions of lung containing tumors as well as non-tumor-containing areas in order to determine if uniform ablations with sharp boundaries could be obtained in human lung. RESULTS: We found that all ablations were anatomically contained. The frequency of uniform ablation effect was dependent on the total energy delivered and was achieved at a greater frequency than those with sharp boundaries. If a lung tumor was contained within the anatomy of the subsegment, the ablation zone completely surrounded the tumor. CONCLUSION: We conclude that BTVA may have a future role in the treatment of lung cancer and should be investigated further in clinical trials.
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Técnicas de Ablación/métodos , Broncoscopía/métodos , Neoplasias Pulmonares/cirugía , Pulmón/cirugía , Vapor , Cadáver , HumanosRESUMEN
BACKGROUND: Infections have been linked to inadequately reprocessed flexible bronchoscopes, and recent investigations determined that pathogen transmission occurred even when bronchoscope cleaning and disinfection practices aligned with current guidelines. This multisite, prospective study evaluated the effectiveness of real-world bronchoscope reprocessing methods, using a systematic approach. METHODS: This study involved direct observation of reprocessing methods for flexible bronchoscopes, multifaceted evaluations performed after manual cleaning and after high-level disinfection, and assessments of storage conditions. Visual inspections of ports and channels were performed using lighted magnification and borescopes. Contamination was detected using microbial cultures and tests for protein, hemoglobin, and adenosine triphosphate (ATP). Researchers assessed reprocessing practices, and storage cabinet cleanliness was evaluated by visual inspection and ATP tests. RESULTS: Researchers examined 24 clinically used bronchoscopes. After manual cleaning, 100% of bronchoscopes had residual contamination. Microbial growth was found in 14 fully reprocessed bronchoscopes (58%), including mold, Stenotrophomonas maltophilia, and Escherichia coli/Shigella species. Visible irregularities were observed in 100% of bronchoscopes, including retained fluid; brown, red, or oily residue; scratches; damaged insertion tubes and distal ends; and filamentous debris in channels. Reprocessing practices were substandard at two of three sites. CONCLUSIONS: Damaged and contaminated bronchoscopes were in use at all sites. Inadequate reprocessing practices may have contributed to bioburden found on bronchoscopes. However, even when guidelines were followed, high-level disinfection was not effective. A shift toward the use of sterilized bronchoscopes is recommended. In the meantime, quality management programs and updated reprocessing guidelines are needed.
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Bacterias , Broncoscopios , Desinfección/métodos , Equipo Reutilizado/normas , Esterilización/métodos , Ultrasonografía Intervencional/instrumentación , Bacterias/clasificación , Bacterias/aislamiento & purificación , Broncoscopios/microbiología , Broncoscopios/normas , Contaminación de Equipos/prevención & control , Humanos , Control de Infecciones/métodos , Técnicas Microbiológicas/métodos , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Mejoramiento de la CalidadRESUMEN
Although average survival rates for lung cancer have improved, earlier and better diagnosis remains a priority. One promising approach to assisting earlier and safer diagnosis of lung lesions is bronchoalveolar lavage (BAL), which provides a sample of lung tissue as well as proteins and immune cells from the vicinity of the lesion, yet diagnostic sensitivity remains a challenge. Reproducible isolation of lung epithelia and multianalyte extraction have the potential to improve diagnostic sensitivity and provide new information for developing personalized therapeutic approaches. We present the use of a recently developed exclusion-based, solid-phase-extraction technique called SLIDE (Sliding Lid for Immobilized Droplet Extraction) to facilitate analysis of BAL samples. We developed a SLIDE protocol for lung epithelial cell extraction and biomarker staining of patient BALs, testing both EpCAM and Trop2 as capture antigens. We characterized captured cells using TTF1 and p40 as immunostaining biomarkers of adenocarcinoma and squamous cell carcinoma, respectively. We achieved up to 90% (EpCAM) and 84% (Trop2) extraction efficiency of representative tumor cell lines. We then used the platform to process two patient BAL samples in parallel within the same sample plate to demonstrate feasibility and observed that Trop2-based extraction potentially extracts more target cells than EpCAM-based extraction.
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Líquido del Lavado Bronquioalveolar/citología , Células Epiteliales/química , Inmunohistoquímica/métodos , Neoplasias Pulmonares/diagnóstico , Manejo de Especímenes/métodos , Biomarcadores de Tumor/análisis , Línea Celular Tumoral , Humanos , Inmunohistoquímica/instrumentación , Manejo de Especímenes/instrumentaciónRESUMEN
IMPORTANCE: Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. OBJECTIVE: To determine the effectiveness and safety of endobronchial coil treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. INTERVENTIONS: Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. MAIN OUTCOMES AND MEASURES: The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St George's Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. RESULTS: Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs -7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to ∞; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to ∞]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to ∞]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to ∞; 1-sided P < .001), and the between-group St George's Respiratory Questionnaire score improved -8.9 points (97.5% CI, -∞ to -6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. CONCLUSIONS AND RELEVANCE: Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01608490.
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Tolerancia al Ejercicio , Prótesis e Implantes/efectos adversos , Enfisema Pulmonar/fisiopatología , Enfisema Pulmonar/terapia , Anciano , Broncoscopía , Femenino , Volumen Espiratorio Forzado , Hospitalización , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Neumonía/etiología , Calidad de Vida , Método Simple Ciego , Resultado del TratamientoRESUMEN
BACKGROUND: Bronchoscopy is frequently used for the evaluation of suspicious pulmonary lesions found on computed tomography, but its sensitivity for detecting lung cancer is limited. Recently, a bronchial genomic classifier was validated to improve the sensitivity of bronchoscopy for lung cancer detection, demonstrating a high sensitivity and negative predictive value among patients at intermediate risk (10-60 %) for lung cancer with an inconclusive bronchoscopy. Our objective for this study was to determine if a negative genomic classifier result that down-classifies a patient from intermediate risk to low risk (<10 %) for lung cancer would reduce the rate that physicians recommend more invasive testing among patients with an inconclusive bronchoscopy. METHODS: We conducted a randomized, prospective, decision impact survey study assessing pulmonologist recommendations in patients undergoing workup for lung cancer who had an inconclusive bronchoscopy. Cases with an intermediate pretest risk for lung cancer were selected from the AEGIS trials and presented in a randomized fashion to pulmonologists either with or without the patient's bronchial genomic classifier result to determine how the classifier results impacted physician decisions. RESULTS: Two hundred two physicians provided 1523 case evaluations on 36 patients. Invasive procedure recommendations were reduced from 57 % without the classifier result to 18 % with a negative (low risk) classifier result (p < 0.001). Invasive procedure recommendations increased from 50 to 65 % with a positive (intermediate risk) classifier result (p < 0.001). When stratifying by ultimate disease diagnosis, there was an overall reduction in invasive procedure recommendations in patients with benign disease when classifier results were reported (54 to 41 %, p < 0.001). For patients ultimately diagnosed with malignant disease, there was an overall increase in invasive procedure recommendations when the classifier results were reported (50 to 64 %, p = 0.003). CONCLUSIONS: Our findings suggest that a negative (low risk) bronchial genomic classifier result reduces invasive procedure recommendations following an inconclusive bronchoscopy and that the classifier overall reduces invasive procedure recommendations among patients ultimately diagnosed with benign disease. These results support the potential clinical utility of the classifier to improve management of patients undergoing bronchoscopy for suspect lung cancer by reducing additional invasive procedures in the setting of benign disease.
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Broncoscopía/métodos , Toma de Decisiones Clínicas , Genómica/métodos , Neoplasias Pulmonares/clasificación , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Bronchoscopy is often the initial diagnostic procedure performed in patients with pulmonary lesions suggestive of lung cancer. A bronchial genomic classifier was previously validated to identify patients at low risk for lung cancer after an inconclusive bronchoscopy. In this study, we evaluated the potential of the classifier to reduce invasive procedure utilization in patients with suspected lung cancer. METHODS: In two multicenter trials of patients undergoing bronchoscopy for suspected lung cancer, the classifier was measured in normal-appearing bronchial epithelial cells from a mainstem bronchus. Among patients with low and intermediate pretest probability of cancer (n = 222), subsequent invasive procedures after an inconclusive bronchoscopy were identified. Estimates of the ability of the classifier to reduce unnecessary procedures were calculated. RESULTS: Of the 222 patients, 188 (85%) had an inconclusive bronchoscopy and follow-up procedure data available for analysis. Seventy-seven (41%) patients underwent an additional 99 invasive procedures, which included surgical lung biopsy in 40 (52%) patients. Benign and malignant diseases were ultimately diagnosed in 62 (81%) and 15 (19%) patients, respectively. Among those undergoing surgical biopsy, 20 (50%) were performed in patients with benign disease. If the classifier had been used to guide decision making, procedures could have been avoided in 50% (21 of 42) of patients undergoing further invasive testing. Further, among 35 patients with an inconclusive index bronchoscopy who were diagnosed with lung cancer, the sensitivity of the classifier was 89%, with 4 (11%) patients having a false-negative classifier result. CONCLUSIONS: Invasive procedures after an inconclusive bronchoscopy occur frequently, and most are performed in patients ultimately diagnosed with benign disease. Using the genomic classifier as an adjunct to bronchoscopy may reduce the frequency and associated morbidity of these invasive procedures. TRIAL REGISTRY: ClinicalTrials.gov; Nos. NCT01309087 and NCT00746759; URL: www.clinicaltrials.gov.
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Bronquios/patología , Broncoscopía/efectos adversos , Pruebas Genéticas/métodos , Neoplasias Pulmonares , Anciano , Biopsia/métodos , Broncoscopía/métodos , Femenino , Genómica/métodos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Objective. Endobronchial ultrasound (EBUS) utility in diagnosis in malignant and granulomatous mediastinal disease has been well demonstrated. We propose to examine the role of EBUS transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of subacute pulmonary histoplasmosis (SPH) with mediastinal lymphadenopathy in an area where histoplasmosis is endemic. Methods. A retrospective review was performed in a single academic institution between 2009 and 2012 of patients referred for EBUS-TBNA who had radiographic imaging and clinical symptomatology suspicious for SPH. Seven patients were reviewed. TBNA results showing granulomatous disease with areas of necrosis in the appropriate clinical setting were considered to be adequate for the diagnosis of SPH when alternative diagnosis was excluded. Patients underwent further clinical follow-up of 12 months to determine the final diagnosis. Results. All seven patients were felt to have SPH diagnosis reached by a combination of clinical presentation, EBUS-TBNA results, fungal serologies, and antigen testing. None of the patients needed further invasive procedures. Conclusions. EBUS-TBNA is a minimally invasive tool that can be used to support a diagnosis of SPH in patients with a high degree of clinical suspicion. EBUS-TBNA should be considered as an adjunctive diagnostic procedure for patients with SPH in an appropriate clinical setting.
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The vegetable leafminer (VLM), Liriomyza sativae (Diptera: Agromyzidae) is a serious pest of vegetable crops and ornamentals worldwide. In cropping systems with inappropriate management strategies, development of resistance to insecticides in leafminers is probable. Chlorpyrifos is a commonly used pesticide for controlling leafminers in Iran, but resistance to this insecticide in leafminers has not been characterized. In order to develop strategies to minimize resistance in the field and greenhouse, a laboratory selected chlorpyrifos resistant strain of L. sativae was used to characterize resistance and determine the rate of development and stability of resistance. Selecting for resistance in the laboratory after 23 generations yielded a chlorpyrifos resistant selected strain (CRSS) with a resistance ratio of 40.34, determined on the larval stage. CRSS exhibited no cross-resistance to other tested insecticides except for diazinon. Synergism and biochemical assays indicated that esterases (EST) had a key role in metabolic resistance to chlorpyrifos, but glutathione S-transferase (GST) and mixed function oxidase (MFO) were not mediators in this resistance. In CRSS acetylcholinesterase (AChE) was more active than the susceptible strain, Sharif (SH). AChE in CRSS was also less sensitive to inhibition by propoxur. The kinetics parameters (Km and Vmax) of AChE indicated that affinities and hydrolyzing efficiencies of this enzyme in CRSS were higher than SH. Susceptibility to chlorpyrifos in L. sativae was re-gained in the absence of insecticide pressure. Synergism, biochemical and cross-resistance assays revealed that overactivity of metabolic enzymes and reduction in target site sensitivity are probably joint factors in chlorpyrifos resistance. An effective insecticide resistance management program is necessary to prevent fast resistance development in crop systems.
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Cloropirifos/toxicidad , Dípteros/efectos de los fármacos , Insecticidas/toxicidad , Acetilcolinesterasa/genética , Animales , Dípteros/enzimología , Dípteros/genética , Resistencia a los Insecticidas/genéticaRESUMEN
BACKGROUND: Various methods for ablating peripheral lung lesions are being investigated; however, none have been successfully adapted for delivery via bronchoscopy. Vapor ablation is currently being used to bronchoscopically create lung volume reduction in emphysema patients. OBJECTIVES: In this study, an adaptation of that technology is evaluated for potential treatment of lung lesions in a live pig model. METHODS: In 5 anesthetized healthy pigs, vapor of varying energy levels was delivered bronchoscopically to 66 different lung subsegments with airway diameters of 2-5 mm. Two hours after treatment, a necropsy was performed and the ablated regions were assessed for ablation and tissue structure disruption. In 6 additional pigs, vapor was applied to 3 subsegments each. To evaluate the progression of the response to treatment, 2 were kept alive for 10 days, 2 for 21 days, and 2 for 32 days. RESULTS: Histopathological evaluation of the sections demonstrated that vapor is capable of creating a uniform field of necrosis following the subsegment anatomical boundary. The reliability of a uniform field is dependent on the level of energy delivered. An energy level that reliably creates a uniform field of necrosis was applied in chronic animals. The animals tolerated the procedure and posttreatment care. No cardiac arrhythmias, hemorrhage, stroke, respiratory distress, or pneumothorax occurred during or after treatment. CONCLUSIONS: Vapor ablation is a potentially safe and efficient means of ablating a targeted region of the lung. We hypothesize that vapor may be useful in treating lesions of the lung in humans.
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Técnicas de Ablación , Broncoscopía/métodos , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Complicaciones Posoperatorias/diagnóstico , Técnicas de Ablación/efectos adversos , Técnicas de Ablación/métodos , Animales , Modelos Animales , Periodo Posoperatorio , Porcinos , Resultado del TratamientoRESUMEN
BACKGROUND: Bronchoscopy is frequently nondiagnostic in patients with pulmonary lesions suspected to be lung cancer. This often results in additional invasive testing, although many lesions are benign. We sought to validate a bronchial-airway gene-expression classifier that could improve the diagnostic performance of bronchoscopy. METHODS: Current or former smokers undergoing bronchoscopy for suspected lung cancer were enrolled at 28 centers in two multicenter prospective studies (AEGIS-1 and AEGIS-2). A gene-expression classifier was measured in epithelial cells collected from the normal-appearing mainstem bronchus to assess the probability of lung cancer. RESULTS: A total of 639 patients in AEGIS-1 (298 patients) and AEGIS-2 (341 patients) met the criteria for inclusion. A total of 43% of bronchoscopic examinations were nondiagnostic for lung cancer, and invasive procedures were performed after bronchoscopy in 35% of patients with benign lesions. In AEGIS-1, the classifier had an area under the receiver-operating-characteristic curve (AUC) of 0.78 (95% confidence interval [CI], 0.73 to 0.83), a sensitivity of 88% (95% CI, 83 to 92), and a specificity of 47% (95% CI, 37 to 58). In AEGIS-2, the classifier had an AUC of 0.74 (95% CI, 0.68 to 0.80), a sensitivity of 89% (95% CI, 84 to 92), and a specificity of 47% (95% CI, 36 to 59). The combination of the classifier plus bronchoscopy had a sensitivity of 96% (95% CI, 93 to 98) in AEGIS-1 and 98% (95% CI, 96 to 99) in AEGIS-2, independent of lesion size and location. In 101 patients with an intermediate pretest probability of cancer, the negative predictive value of the classifier was 91% (95% CI, 75 to 98) among patients with a nondiagnostic bronchoscopic examination. CONCLUSIONS: The gene-expression classifier improved the diagnostic performance of bronchoscopy for the detection of lung cancer. In intermediate-risk patients with a nondiagnostic bronchoscopic examination, a negative classifier score provides support for a more conservative diagnostic approach. (Funded by Allegro Diagnostics and others; AEGIS-1 and AEGIS-2 ClinicalTrials.gov numbers, NCT01309087 and NCT00746759.).