Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Low bleeding rates following transbronchial lung cryobiopsy in unclassifiable interstitial lung disease.

BACKGROUND AND OBJECTIVE: Bronchoscopic transbronchial lung cryobiopsy (TBLC) is a guideline-endorsed alternative to surgical lung biopsy for tissue diagnosis in unclassifiable interstitial lung disease (ILD). The reported incidence of post-procedural bleeding has varied widely. We aimed to characterize the incidence, severity and risk factors for clinically significant bleeding following TBLC using an expert-consensus airway bleeding scale, in addition to other complications and diagnostic yield. METHODS: A retrospective cohort study of consecutive adult outpatients with unclassifiable ILD who underwent TBLC following multidisciplinary discussion at a single centre in the UK between July 2016 and December 2021. TBLC was performed under general anaesthesia with fluoroscopic guidance and a prophylactic endobronchial balloon. RESULTS: One hundred twenty-six patients underwent TBLC (68.3% male; mean age 62.7 years; FVC 86.2%; DLCO 54.5%). Significant bleeding requiring balloon blocker reinflation for >20 min, admission to ICU, packed red blood cell transfusion, bronchial artery embolization, resuscitation or procedural abandonment, occurred in 10 cases (7.9%). Significant bleeding was associated with traction bronchiectasis on HRCT (OR 7.1, CI 1.1-59.1, p = 0.042), a TBLC histological pattern of UIP (OR 4.0, CI 1.1-14, p = 0.046) and the presence of medium-large vessels on histology (OR 37.3, CI 6.5-212, p < 0.001). BMI ≥30 (p = 0.017) and traction bronchiectasis on HRCT (p = 0.025) were significant multivariate predictors of longer total bleeding time (p = 0.017). Pneumothorax occurred in nine cases (7.1%) and the 30-day mortality was 0%. Diagnostic yield was 80.6%. CONCLUSION: TBLC has an acceptable safety profile in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding following TBLC.

Integral mediastinal staging in patients with NON-SMALL cell lung cancer and risk factors for occult N2 disease.

BACKGROUND: In patients with non-small cell lung cancer (NSCLC), the presence of abnormal hiliar lymph nodes (clinical N1; cN1), central tumor location and/or tumor size (diameter >3 cm) increases the risk of occult mediastinal metastasis (OMM). This study investigates prospectively the diagnostic value of an integral mediastinal staging (IMS) strategy that combines EndoBronchial Ultrasound-TransBronchial Needle Aspiration (EBUS-TBNA) and Video-Assisted Mediastinoscopy (VAM) in patients with NSCLC at risk of OMM. METHODS: Patients with NSCLC and radiologically normal mediastinum assessed non-invasively by positron emission tomography and computed tomography of the chest (PET-CT), and OMM risk factors (cN1, central tumor and/or >3 cm) underwent EBUS-TBNA followed by VAM if the former was negative. Those with negative IMS underwent resection surgery of the tumor. RESULTS: EBUS-TBNA identified OMM in 2 out of the 49 patients evaluated (4%) and VAM in 1 of the 47 patients with negative EBUS (2%). Two patients with a negative IMS had OMM at surgery. Overall, the prevalence of OMM was 10%. EBUS-TBNA has a sensitivity of 40%, a negative predictive value (NPV) of 93.6%, and negative likelihood ratio of 0.60 (95%CI:0.30-1.16). The risk of not diagnosing OMM after EBUS was 6% and after IMS was 4.4%. CONCLUSION: Integral mediastinal staging in patients with NSCLC and clinical risk factors for OMM, does not seem to provide added diagnostic value to that of EBUS-TBNA, except perhaps in patients with cN1 disease who deserve further research.

EBUS-TBNA in Extrathoracic Malignancies: Diagnostic and Prognostic Implications.

PURPOSE: In patients with extrathoracic malignancies (EM) the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the assessment of abnormal mediastinal lymph nodes (MLN) is controversial. The aim of this study was to assess the diagnostic yield and prognostic significance of EBUS-TBNA in these patients. METHODS: Retrospective analysis of patients with EM and abnormal MLN detected by Computed Tomography (CT) and/or Positron Emission Tomography (PET). RESULTS: A total of 161 patients with EM and abnormal MLN were included (93 males, 58%). The most common EM was melanoma (19%) and gastrointestinal cancer (17%). Assessed lymph nodes were mediastinal in 70% of cases and hilar in 30%. The most frequently sampled lymph nodes were subcarinal (45%) and lower right paratracheal (21%). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EBUS-TBNA for the diagnosis of malignancy were 88%, 100%, 100% and 87%, respectively. These values were similar regardless the type of EM except for head and neck tumors where the NPV was particularly low (67%). The diagnosis of neoplastic involvement by EBUS-TBNA implied a worse prognosis in terms of overall survival (p < 0.02) and cancer-specific survival (p < 0.001). CONCLUSIONS: In patients with EM and abnormal MLN, EBUS-TBNA has a high diagnostic yield. However, the NPV decrease in patients with head and neck tumors. Neoplastic MLN detected by EBUS-TBNA has prognostic implications in these patients.

Safety and Feasibility of Transbronchial Cryobiopsy in Mechanically Ventilated Patients

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Pathological response to neoadjuvant therapy with chemotherapy vs chemoradiotherapy in stage III NSCLC-contribution of IASLC recommendations.

BACKGROUND: Neoadjuvant treatment (NT) with chemotherapy (Ch) is a standard option for resectable stage III (N2) NSCLC. Several studies have suggested benefits with the addition of radiotherapy (RT) to NT Ch. The International Association for the Study of Lung Cancer (IASLC) published recommendations for the pathological response (PHR) of NSCLC resection specimens after NT. AIM: To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy (ChRT). METHODS: We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020. After NT, all patients were evaluated for radiological response (RR) according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons. All histological samples were examined by the same two pathologists. PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes. RESULTS: Forty patients underwent NT ChRT and 27 NT Ch. Fifty-six (83.6%) patients underwent surgery (35 ChRT and 21 Ch). The median time from ChRT to surgery was 6 wk (3-19) and 8 wk (3-21) for Ch patients. We observed significant differences in RR, with disease progression in 2.5% and 14.8% of patients with ChRT and Ch, respectively, and partial response in 62.5% ChRT vs 29.6% Ch (P = 0.025). In PHR we observed ≤ 10% viable cells in the tumor in 19 (54.4%) and 2 cases (9.5%), and in the resected lymph nodes (RLN) 30 (85.7%) and 7 (33.3%) in ChRT and Ch, respectively (P = 0.001). Downstaging was greater in the ChRT compared to the Ch group (80% vs 33.3%; P = 0.002). In the univariate analysis, NT ChRT had a significant impact on partial RR [odds ratio (OR) 12.5; 95% confidence interval (CI): 1.21 - 128.61; P = 0.034], a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5% increased probability for achieving downstaging (OR 8; 95%CI: 2.34-27.32; P = 0.001). CONCLUSION: We found significant benefits in RR and PHR by adding RT to Ch as NT. A longer follow-up is necessary to assess the impact on clinical outcomes.

EBUS-TBNA Cytological Samples for Comprehensive Molecular Testing in Non-Small Cell Lung Cancer.

Clinical guidelines promote the identification of several targetable biomarkers to drive treatment decisions in advanced non-small cell lung cancer (NSCLC), but half of all patients do not have a viable biopsy. Specimens from endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) are an alternative source of material for the initial diagnosis of NSCLC, however their usefulness for a complete molecular characterization remains controversial. EBUS-TBNA samples were prospectively tested for several biomarkers by next-generation sequencing (NGS), nCounter, and immunohistochemistry (PD-L1). The primary objectives were to assess the sensitivity of EBUS-TBNA samples for a comprehensive molecular characterization and to compare its performance to the reference standard of biopsy samples. Seventy-two EBUS-TBNA procedures were performed, and 42 NSCLC patients were diagnosed. Among all cytological samples, 92.9% were successfully genotyped by NGS, 95.2% by nCounter, and 100% by immunohistochemistry. There were 29 paired biopsy samples; 79.3% samples had enough tumor material for genomic genotyping, and 96.6% for PD-L1 immunohistochemistry. A good concordance was found between both sources of material: 88.9% for PD-L1, 100% for NGS and nCounter. EBUS-TBNA is a feasible alternative source of material for NSCLC genotyping and allows the identification of patient candidates for personalized therapies with high concordance when compared with biopsy.

Mediastinitis focal con trombosis arterial pulmonar asociada tras EBUS-TBNA / Focal Mediastinitis and Pulmonary Arterial Thrombosis after EBUS-TBNA

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Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services.

BACKGROUND: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. METHODS: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. RESULTS: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. CONCLUSIONS: The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images.

Is invasive mediastinal staging necessary in intermediate risk patients with negative PET/CT?

BACKGROUND: Tumor involvement of mediastinal lymph nodes is of high importance in non-small cell lung cancer (NSCLC). Invasive mediastinal staging is recommended in selected patients without evidence of mediastinal involvement on staging by imaging. In the present study we aimed to evaluate the effectiveness of invasive mediastinal staging in reducing pN2, its impact on survival and the risk factors for occult pN2. METHODS: Patients with NSCLC tumors larger than 3 cm, central tumors or cN1 cases treated in our institution between 2013 and 2018 were prospectively included in the study. Incidence of pN2 and overall survival was compared among invasively staged (IS) and non-invasively staged groups (NIS). Multivariate analysis was performed to identify risk factors of pN2. RESULTS: A total of 201 patients were included in the study, 79 (39.3%) of whom were not invasively staged (NIS group) and 122 (60.7%) were invasively staged (IS group). Incidence of cN1 and mean PET/CT uptake was different among both groups. Prevalence of pN2 was similar in both groups (7.6% in NIS vs. 12.6% in IS; P>0.05). Median survival in IS-pN2 patients was 11 months longer than in NIS-pN2 group (33.6 vs. 22.5 months; P=0.245). cN1 emerged as the only a risk factor for pN2. CONCLUSIONS: Invasive staging does not reduce the incidence of pN2. However, this finding could be biased because in our series cN1 patients were more often staged and cN1 has been detected as a risk factor for pN2. In addition patient better selection after invasive staging might have an impact on overall survival. To conclude, invasive mediastinal staging in intermediate risk patients for positive mediastinal nodes is justified.

Impact of a systematic evaluation of connective tissue disease on diagnosis approach in patients with interstitial lung diseases.

To date, there is no clear agreement regarding which is the best method to detect a connective tissue disease (CTD) during the initial diagnosis of interstitial lung diseases (ILD). The aim of our study was to explore the impact of a systematic diagnostic strategy to detect CTD-associated ILD (CTD-ILD) in clinical practice, and to clarify the significance of interstitial pneumonia with autoimmune features (IPAF) diagnosis in ILD patients.Consecutive patients evaluated in an ILD Diagnostic Program were divided in 3 groups: IPAF, CTD-ILD, and other ILD forms. Clinical characteristics, exhaustive serologic testing, high resolution computed tomography (HRCT) images, lung biopsy specimens, and follow-up were prospectively collected and analyzed.Among 139 patients with ILD, CTD was present in 21 (15.1%), 24 (17.3%) fulfilled IPAF criteria, and 94 (67.6%) were classified as other ILD forms. Specific systemic autoimmune symptoms such as Raynaud phenomenon (19%), inflammatory arthropathy (66.7%), and skin manifestations (38.1%) were more frequent in CTD-ILD patients than in the other groups (all P < .001). Among autoantibodies, antinuclear antibody was the most frequently found in IPAF (42%), and CTD-ILD (40%) (P = .04). Nonspecific interstitial pneumonia, detected by HRCT scan, was the most frequently seen pattern in patients with IPAF (63.5%), or CTD-ILD (57.1%) (P < .001). In multivariate analysis, a suggestive radiological pattern by HRCT scan (odds ratio [OR] 15.1, 95% confidence interval [CI] 4.7-48.3, P < .001) was the strongest independent predictor of CTD-ILD or IPAF, followed by the presence of clinical features (OR 14.6, 95% CI 4.3-49.5, P < .001), and serological features (OR 12.4, 95% CI 3.5-44.0, P < .001).This systematic diagnostic strategy was useful in discriminating an underlying CTD in patients with ILD. The defined criteria for IPAF are fulfilled by a considerable proportion of patients referred for ILD.

Linfoepitelioma-like primario pulmonar en paciente no asiático / Primary Pulmonary Lymphoepithelioma-Like Carcinoma in a Non-Asian Patient

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Auscultation of Velcro Crackles is Associated With Usual Interstitial Pneumonia.

Auscultation of Velcro crackles has been proposed as a key finding in physical lung examination in patients with interstitial lung diseases (ILDs), especially in idiopathic pulmonary fibrosis (IPF). However, no studies have been carried out to assess the association of Velcro crackles with other clinical variables.We evaluated a cohort of 132 patients, prospectively and consecutively included in our ILD diagnostic program at a tertiary referral center. All patients were auscultated during the physical examination. The patients were divided into 2 groups: "presence" or "nonpresence" of bilateral Velcro crackles.Of all patients assessed, 83 (63%) presented Velcro crackles in the respiratory auscultation. Patients with Velcro crackles usually had more frequently cough and dyspnea at the moment of diagnosis. Forced vital capacity (P = 0.002) and lung diffusion capacity for carbon monoxide (P = 0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (P = 0.01). All patients with usual interstitial pneumonia (UIP) in high-resolution computed tomography and all patients with final IPF diagnosis presented Velcro crackles. In multivariate analysis, the presence of Velcro crackles was independently associated with an UIP pattern.In patients suspected of having ILD, the auscultation of Velcro crackles was associated with UIP, a possibility which must be taken into consideration in early ILD detection in primary care.

Utilidad de la criobiopsia en el diagnóstico de la enfermedad pulmonar intersticial difusa: análisis de rentabilidad y coste / Cryobiopsy in the Diagnosis of Diffuse Interstitial Lung Disease: Yield and Cost-Effectiveness Analysis

Introducción: En los pacientes con enfermedad pulmonar intersticial difusa (EPID) que presentan datos clínicos y radiológicos inconsistentes es recomendable la realización de una biopsia pulmonar quirúrgica (BPQ). La criobiopsia es una técnica endoscópica reciente menos invasiva que la BPQ que podría jugar un papel relevante en el diagnóstico de las EPID. El objetivo del presente estudio es analizar la rentabilidad diagnóstica, las complicaciones y los costes económicos derivados del uso de la criobiopsia en el diagnóstico de las EPID. Métodos: Estudio observacional retrospectivo en el que se incluyeron pacientes afectados de EPID tributarios de biopsia pulmonar, a los que se les practicaron criobiopsias desde enero de 2011 a enero de 2014. El procedimiento se realizó mediante videobroncoscopio, bajo anestesia general y ventilación mecánica. Se analizó la rentabilidad diagnóstica, las complicaciones producidas y los costes económicos derivados de esta técnica. Resultados: Se analizaron las muestras de criobiopsia de un total de 33 pacientes. Se obtuvo un diagnóstico específico en 26, lo que representa una rentabilidad diagnóstica del 79%. Cinco pacientes hubieran requerido BPQ para confirmación histológica, aunque en 4 de ellos no pudo realizarse por presentar comorbilidades graves. Las complicaciones más frecuentes fueron el neumotórax (12%) y el sangrado moderado (21%). No hubo complicaciones graves. Considerando que a los pacientes con diagnóstico específico se les evitó unaBPQ, la criobiopsia representó unahorro económico estimado dehasta 59.846 Euros. Conclusiones: La criobiopsia es una técnica segura y potencialmente útil en el diagnóstico de las EPID que permite, además, un ahorro económico considerable

Background: Assessment of patients with suspected interstitial lung disease (ILD) includes surgical lung biopsy (SLB) when clinical and radiological data are inconclusive. However, cryobiopsy is acquiring an important role in the ILD diagnostic process. The objective of this study was to evaluate the diagnostic yield, safety and economic costs of the systematic use of cryobiopsy in the assessment of patients with suspected ILD. Methods: This was a retrospective observational study of patients who had undergone transbronchial cryobiopsy for evaluation of ILD from January 2011 to January 2014. The procedures were performed with a video bronchoscope using a cryoprobe for the collection of lung parenchyma specimens, which were analyzed by pathologists. Diagnostic yield, complications and economic costs ofthis technique were analyzed Results: Criobiopsy specimens from a total of 33 patients were included. A specific diagnosis was obtained in 26, producing a diagnostic yield of 79%. In 5 patients, SLB was required for a histopathological confirmation of disease, but the procedure could not be performed in 4, due to severe comorbidities. The most frequent complications were pneumothorax (12%) and grade i (9%) or grade ii (21%) bleeding. There were no life-threatening complications. The systematic use of cryobiopsy saved up to 59,846 Euros. Conclusion: Cryobiopsy is a safe and potentially useful technique in the diagnostic assessment