José Sanz-Santos

Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations

The presence of somatic mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in patients with advanced nonsmall cell lung cancer (NSCLC) correlates with a good response to tyrosine kinase inhibitors. The usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the detection of EGFR mutations in cells recovered from malignant mediastinal nodes in patients with NSCLC was assessed. All patients with lung adenocarcinoma or unspecified NSCLC referred for staging with EBUS-TBNA were included. Nodes with a short-axis diameter of >5 mm were sampled, and genomic DNA from metastatic tumour cells was obtained for analysis of exons 19 and 21. The impact of sampling on management was assessed. EGFR gene analysis of the EBUS-TBNA sample was feasible in 26 (72.2%) out of the 36 patients with lymph node metastasis. Somatic mutations of the EGFR gene were detected in tissue obtained through EBUS-TBNA in two (10%) out of 20 patients with metastasic lung adenocarcinoma. Malignant tissue samples obtained by EBUS-TBNA from patients with nodal metastasis of NSCLC are suitable for the detection of EGFR mutations in most cases, and this technique demonstrates mutated neoplastic cells in a tenth of patients with adenocarcinoma.

Contribution of cell blocks obtained through endobronchial ultrasound-guided transbronchial needle aspiration to the diagnosis of lung cancer.

BackgroundConventional smears of samples obtained by endobronchial ultrasound with real-time transbronchial needle aspiration (EBUS-TBNA) have proven useful in lung cancer staging, but the value of additional information from cell-block processing of EBUS-TBNA samples has only been marginally investigated. This study focussed on the contribution of cell block analysis to the diagnostic yield in lung cancer.MethodsPatients referred for lung cancer diagnosis and/or staging by means of EBUS-TBNA were enrolled, the adequacy of the obtained samples for preparing cell blocks was assessed, and the additional pathologic or genetic information provided from cell block analysis was examined.ResultsIn 270 lung cancer patients referred for EBUS-TBNA (mean age, 63.3 SD 10.4 years) 697 aspirations were performed. Cell blocks could be obtained from 334 aspirates (47.9%) and contained diagnostic material in 262 (37.6%) aspirates, providing information that was additional to conventional smears in 50 of the 189 samples with smears that were non-diagnostic, corresponding 21 of these blocks to malignant nodes, and allowing lung cancer subtyping of 4 samples. Overall, cell blocks improved the pathologic diagnosis attained with conventional smears in 54 of the 697 samples obtained with EBUS-TBNA (7.7%). Cell blocks obtained during EBUS-TBNA also made epithelial growth factor receptor mutation analysis possible in 39 of the 64 patients with TBNA samples showing metastatic adenocarcinoma (60.1%). Overall, cell blocks provided clinically significant information for 83 of the 270 patients participating in the study (30.7%).ConclusionsCell-block preparation from EBUS-TBNA samples is a simple way to provide additional information in lung cancer diagnosis. Analysis of cell blocks increases the diagnostic yield of the procedure by nearly seven per cent and allows for genetic analysis in a sixty per cent of the patients with metastatic adenocarcinoma.

La ultrasonografía endobronquial lineal como instrumento de diagnóstico inicial en el paciente con ocupación mediastínica

BACKGROUND AND OBJECTIVE Linear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven useful for sampling mediastinal masses and nodes and for staging lung cancer. The aim of this study was to assess the usefulness of this diagnostic tool in patients with indications of mediastinal disease that could not be diagnosed by noninvasive methods or white light bronchoscopy. PATIENTS AND METHODS All patients undergoing linear EBUS-TBNA for the diagnosis of mediastinal masses and/or adenopathy at our endoscopy unit were included in the study. Diagnoses obtained by linear EBUS-TBNA or any surgical technique performed after a nondiagnostic EBUS-TBNA were considered as final. RESULTS In the study population of 128 patients with a mean (SD) age of 62.0 (11.2) years, a total of 294 TBNAs were performed on 12 masses and 282 nodes. Satisfactory samples were obtained in 11 cases (91.7%) from masses and in 233 cases (82.6%) from nodes. Linear EBUS-TBNA was diagnostic, obviating the need for mediastinoscopy in 115 patients (diagnostic sensitivity, 89.8%). The technique confirmed the diagnosis in 85 of the 94 patients with cancer (90.4%), in 8 of the 10 patients with tuberculosis (80.0%), and in the 5 patients with sarcoidosis. CONCLUSIONS Linear EBUS-TBNA is a useful diagnostic tool in patients with mediastinal disease for whom a pathologic diagnosis is not achieved by noninvasive methods or white light bronchoscopy.

Utilidad de una consulta monográfica de diagnóstico rápido de cáncer de pulmón. Aportaciones de la ecobroncoscopia

OBJECTIVE To analyse the results obtained in the diagnosis and staging of lung cancer (LC) by a Lung Cancer Rapid Diagnosis Unit (LC-RDU) in which real-time endobronchial ultrasound-guided transbronchial needle aspiration (RT-EBUS guided-TBNA) is performed as part of the clinical evaluation of the patient prior to treatment. METHOD A four year observational study was conducted on a group of patients evaluated due to suspicion of LC in an LC-RDU. The times and the techniques required for the diagnosis and identifying the level of the disease in the initial staging were recorded. RESULTS Out of a total of 678 patients seen in the LC-RDU, the diagnosis in 352 was confirmed in one or more histopathology samples. In 170 patients (48.2%) the diagnosis was made with biopsies and/ or cytology samples obtained by fibrobronchoscopy, and RT-EBUS guided-TBNA confirmed the clinical suspicion in 70 patients (19.9%). In the 280 patients with SCLC, 166 RT-EBUS guided-TBNA were performed for staging (59.3%), and in 105 of them the technique only showed local disease (37.5%). Therapeutic surgery was performed on 83 of these patients, and was radical in 73 cases (87.9%). CONCLUSION In half of the patients referred to the LC-RDU due to suspected LC, the diagnosis was confirmed in 75% of cases using endoscopic techniques. RT-EBUS guided-TBNA was the diagnostic technique in 20% of the cases, for staging in more than half of them, and led to reduced waiting times for the diagnosis and starting treatment.

Usefulness of a lung cancer rapid diagnosis specialist clinic. Contribution of ultrasound bronchoscopy

Abstract Objective To analyse the results obtained in the diagnosis and staging of lung cancer (LC) by a Lung Cancer Rapid Diagnosis Unit (LC-RDU) in which real-time endobronchial ultrasound-guided transbronchial needle aspiration (RT-EBUS guided-TBNA) is performed as part of the clinical evaluation of the patient prior to treatment. Method A four year observational study was conducted on a group of patients evaluated due to suspicion of LC in an LC-RDU. The times and the techniques required for the diagnosis, the treatment period and the level of the disease in the initial staging were recorded. Results Out of a total of 678 patients seen in the LC-RDU, the diagnosis in 352 was confirmed in one or more histopathology tests. In 170 patients (48.2%) the diagnosis was made with biopsies and/ or cytology samples obtained by fibrobronchoscopy, and RT-EBUS guided-TBNA confirmed the clinical suspicion in 70 patients (19.9%). In the 280 patients with NSCLC, 166 RT-EBUS guided-TBNA were performed for staging (59.3%), and in 105 of them the technique only showed local disease (37.5%). Eighty-three of these patients underwent therapeutic surgery, which was radical in 73 cases (87.9%). Conclusion In half of the patients referred to the LC-RDU due to suspected LC, the diagnosis was confirmed in 75% of cases using endoscopic techniques. RT-EBUS guided-TBNA, which was the diagnostic technique in 20% of the cases and for staging in more than half of them, led to reduced waiting times to diagnosis and onset to treatment.

Results of Bronchial Artery Embolization for the Treatment of Hemoptysis Caused by Neoplasm

PURPOSE To describe experience with bronchial artery embolization (BAE) in a cohort of patients with cancer. MATERIALS AND METHODS All consecutive patients with cancer and at least one episode of hemoptysis that required BAE during a 14-year period were included in this observational retrospective review. The endpoints of the study were immediate success, recurrence of hemoptysis, mortality resulting from hemoptysis, and all-cause mortality. RESULTS Immediate control of bleeding was achieved in 31 of 40 patients (77.5%). Recurrence requiring BAE occurred in eight patients (20%). Cumulative hemoptysis control rate was 0.90 (95% confidence interval [CI], 0.80-1.0) at 1 month and 0.65 (95% CI, 0.44-0.86) at 6 months. Probability of survival was 0.75 (95% CI, 0.62-0.88) at 1 month, 0.42 (95% CI, 0.27-0.57) at 6 months, 0.36 (95% CI, 0.21-0.51) at 12 months, and 0.08 (95% CI, 0.0-0.18) at 3 years. CONCLUSIONS BAE is an effective and safe technique in the treatment of hemoptysis in patients with cancer. Nevertheless, mortality resulting from hemoptysis and recurrence rate are high among these patients secondary to progression of the underlying disease.

REPRESENTATIVENESS OF NODAL SAMPLING WITH ENDOBRONCHIAL ULTRASONOGRAPHY IN NON-SMALL-CELL LUNG CANCER STAGING

The objective of our study was to determine the procedure-related requirements of mediastinal node sampling with endobronchial ultrasonography with real-time transbronchial needle aspiration (EBUS-TBNA) that would provide negative predictive value (NPV) for the identification of stage III disease in non-small-cell lung cancer (NSCLC) high enough to consider the technique equivalent to cervical mediastinoscopy. Representative EBUS-TBNA was defined as a sampling procedure obtaining satisfactory samples from normal nodes in regions 4R, 4L and 7 or diagnosing malignancy in mediastinal nodes. NPV was estimated using the results of postsurgical staging in patients who underwent surgery as a reference. Two-hundred ninety-six patients staged with EBUS-TBNA were included. Representative samples from regions 4R, 4L and 7 showing nonmalignant cytology were obtained from 98 patients (33.1%) and EBUS-TBNA detected N2/N3 disease in 150 (50.7%). Accordingly, an EBUS-TBNA procedure accomplishing the representativeness criteria required for sampling was attained in 248 of the participating patients (83.8%). The NPV of the procedure in this setting was 93.6%, with false-negative results only found in 5 patients, four of them with nodal metastasis out of the reach of EBUS-TBNA (regions 5, 8 and 9). In conclusion, representative sampling of regions 4R, 4L and 7 is achieved in more than 80% of patients staged using EBUS-TBNA, and in the procedures that attain this requirement a NPV >90% for mediastinal malignancy is reached, a figure equivalent to cervical mediastinoscopy.

Linear Endobronchial Ultrasound as the Initial Diagnostic Tool in Patients With Indications of Mediastinal Disease

Abstract Introduction Linear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven useful for sampling mediastinal masses and nodes and staging lung cancer. The aim of this study was to assess the usefulness of this diagnostic tool in patients with indications of mediastinal disease that could not be diagnosed by noninvasive methods or white light bronchoscopy. Patients and Methods All patients undergoing linear EBUS-TBNA for the diagnosis of mediastinal masses and/or adenopathy at our endoscopy unit were included in the study. Diagnoses obtained by linear EBUSTBNA or any surgical technique performed after a nondiagnostic EBUS-TBNA were considered as final. Results In the study population of 128 patients with a mean (SD) age of 62.0 (11.2) years, a total of 294 TBNAs were performed on 12 masses and 282 nodes. Satisfactory samples were obtained in 11 cases (91.7%) from masses and in 233 cases (82.6%) from nodes. Linear EBUS-TBNA was diagnostic, obviating the need for mediastinoscopy in 115 patients (diagnostic sensitivity, 89.8%). The technique confirmed the diagnosis in 85 of the 94 patients with cancer (90.4%), in 8 of the 10 patients with tuberculosis (80.0%), and in the 5 with sarcoidosis. Conclusions Linear EBUS-TBNA is a useful diagnostic tool in patients with mediastinal disease for whom a pathologic diagnosis is not achieved by noninvasive methods or white light bronchoscopy.

Bronchial stump aspergillosis after lobectomy for lung cancer as an unusual cause of false positive fluorodeoxyglucose positron emission tomography and computed tomography: a case report

IntroductionBronchial stump aspergillosis is a rare entity characterized by cough and hemoptysis.Case presentationWe report the case of a 58-year-old Caucasian woman who developed bronchial stump aspergillosis two years after a left upper lobe resection for lung cancer. Bronchial stump aspergillosis was diagnosed as a result of a focus of increased fluorodeoxyglucose activity in a follow-up positron emission tomography and computed tomography scan. She was treated with oral antifungal therapy and presented with good evolution after three months of treatment.ConclusionBronchial stump aspergillosis is an unusual complication after pulmonary resection. Clinicians should be aware of it when a local recurrence of cancer around the bronchial stump is suspected based on a positive positron emission tomography and computed tomography finding.

Determinants of false-negative results in non-small-cell lung cancer staging by endobronchial ultrasound-guided needle aspiration

OBJECTIVES False-negative results of endobronchial ultrasound-guided transbronchial needle aspiration in non-small-cell lung cancer staging have shown significant variability in previous studies. The aim of this study was to identify procedure- and tumour-related determinants of endobronchial ultrasound-guided transbronchial needle aspiration false-negative results. METHODS We conducted a prospective study that included non-small-cell lung cancer patients staged as N0/N1 by endobronchial ultrasound-guided transbronchial needle aspiration and undergoing therapeutic surgery. The frequency of false-negative results in the mediastinum was calculated. Procedure-related, first, and tumour-related, second, determinants of false-negative results in stations reachable and non-reachable by endobronchial ultrasound were determined by multivariate logistic regression. RESULTS False-negative endobronchial ultrasound-guided transbronchial needle aspiration results were identified in 23 of 165 enrolled patients (13.9%), mainly in stations reachable by endobronchial ultrasound (17 cases, 10.3%). False-negative results were related to the extensiveness of endobronchial ultrasound sampling: their prevalence was low (2.4%) when sampling of three mediastinal stations was satisfactory, but rose above 10% when this requirement was not fulfilled (P = 0.043). In the multivariate analysis, abnormal mediastinum on computer tomography/positron emission tomography [odds ratio (OR) 7.77, 95% confidence interval (CI) 2.19-27.51, P = 0.001] and extensiveness of satisfactory sampling of mediastinal stations (OR 0.37, 95% CI 0.16-0.89, P = 0.026) were statistically significant risk factors for false-negative results in stations reachable by endobronchial ultrasound. False-negative results in non-reachable nodes were associated with a left-sided location of the tumour (OR 10.11, 95% CI 1.17-87.52, P = 0.036). CONCLUSIONS The presence of false-negative ultrasound-guided transbronchial needle aspiration results were observed in nearly 15% of non-small-cell lung cancer patients but in only 3% when satisfactory samples were obtained from three mediastinal stations. False-negative results in stations reachable by endobronchial ultrasound were associated with the extensiveness of sampling, and in stations out of reach of endobronchial ultrasound with left-sided tumours. These results suggest that satisfactory sampling of at least three mediastinal stations by EBUS-TBNA may be a quality criterion to be recommended for EBUS-TBNA staging.