Search Results (47)

Background/Objectives: Lung cancer is a highly diverse disease, and reliable preclinical models that accurately reflect tumor characteristics are essential for studying lung cancer biology and testing new therapies. This study aimed to establish patient-derived tumor organoids (PDTOs) using small biopsy samples and surgical specimens to create a model system that preserves the genetic and histological features of the original tumors. Methods: PDTOs were generated from 163 lung cancer specimens, including 109 samples obtained using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or bronchoscopy, 52 surgical specimens, and 2 pleural fluid samples. The organoid establishment rate beyond passage three was assessed, and histological subtypes and genetic profiles were analyzed using immunohistochemical staining and targeted exome sequencing. Results: The overall PDTO establishment rate was 34.4% (56/163), and 44.6% (25/56) of these organoids retained the histological and genetic features of the parental tumors. Genetic analysis identified key mutations, including KRAS G12C, EGFR L858R, MET exon 14 skipping mutation, and ROS1 fusion. PDTOs successfully formed tumors in mice while maintaining the genetic characteristics of the original tumors. Co-culture of PDTOs with cancer-associated fibroblasts (CAFs) resulted in increased resistance to paclitaxel. In the co-culture model of PDTOs with immune cells, dose-dependent growth inhibition of PDTOs was observed in response to immune checkpoint inhibitors. Conclusions: PDTOs established from small biopsy and surgical specimens serve as a valuable model for studying lung cancer biology, tumor microenvironment interactions, and drug response. This model has the potential to improve personalized treatment strategies. Full article

Background/Objectives: Recent advances in the treatment of non-small cell lung cancer (NSCLC) have shifted from conventional chemotherapy to targeted therapies aimed at specific genetic mutations, particularly in the adenocarcinoma subtype. These therapies have improved overall survival and quality of life. However, some patients still face barriers to accessing these treatments due to challenges in diagnosing advanced-stage NSCLC. Limited tumor cellularity in small biopsies and cytological samples hinders the ability to perform further molecular analyses. Additionally, the increasing number of genetic alterations requiring testing complicates the diagnostic process. To overcome this challenge, we propose combining endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with next-generation sequencing (NGS) and immunohistochemistry for PD-L1. Methods: A total of 120 EBUS-TBNA samples were consecutively collected during the first year of integrating NGS at a reference hospital in Castilla y León, Spain. Depending on the histology and patient characteristics, a total of 67 NGS analyses and 116 PD-L1 determinations were performed. Results: The cytological sample obtained in these cases successfully achieved the triple objective proposed by the NCCN for lung cancer (diagnosis, staging, and molecular analysis in a single procedure) in 97% of instances. Conclusions: Our study highlights the effectiveness of EBUS-TBNA as a comprehensive, cost-effective, and safe diagnostic tool for NSCLC, successfully achieving the triple objective of diagnosis, staging, and molecular analysis in 97% of cases. The procedure consistently provided high-quality samples for NGS and PD-L1 testing, with minimal complications, reinforcing its value as a reliable approach for optimizing personalized treatment strategies. Full article

Background: The evolution of interventional pulmonology has necessitated the refinement of anesthetic techniques to ensure the safety and efficacy of procedures such as endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), particularly when performed outside the conventional operating room setting. The management of anesthesia in patients with significant comorbidities, classified as American Society of Anesthesiologists (ASA) class III, presents distinct challenges. In this context, the transtracheal block emerges as a viable alternative to total intravenous anesthesia (TIVA) for these high-risk procedures. Objectives: This study aims to evaluate the comparative safety and efficacy of opioid-based intravenous analgesia versus a regimen combining sedative agents with transtracheal block in the administration of anesthesia for EBUS TBNA in high-risk patients. Design: We conducted a randomized observational study involving 57 elective EBUS-TBNA patients classified as ASA class III. Methods: Participants were allocated into two cohorts: one receiving intravenous opioid analgesia and the other receiving a combination of sedative agents with transtracheal block. Collected data encompassed patient demographics, medical history, incidence of adverse events during anesthesia, indicators of sympathetic nervous system activation, patient satisfaction levels, and the procedural conditions as assessed by the operator. Results: Opioid anesthesia was associated with increased desaturation (95.7% vs. 60.6%; p < 0.05) and higher pain-related sympathetic responses (VAS and SCI at 40–100; p < 0.05). No differences in other adverse events, patient satisfaction, or procedural conditions were noted. Conclusions: In summary, the study indicates that transtracheal block combined with sedatives may be a safer anesthetic alternative to opioid-based regimens for high-risk EBUS-TBNA patients, reducing desaturation and pain-related sympathetic activity without affecting satisfaction or procedural efficacy. Full article

We describe the case of a 67-year-old man with lung cancer, who developed pulmonary tuberculosis (TB) following chemotherapy and subsequently exhibited a paradoxical reaction on positron emission tomography/computed tomography (PET/CT) after initiating antituberculosis therapy. While pulmonary consolidations improved with antituberculosis treatment, newly detected hypermetabolic mediastinal lymph nodes appeared on PET/CT. Based on the clinical course, we provisionally concluded that the mediastinal lymphadenopathy represented a paradoxical reaction. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) confirmed the diagnosis of TB. Clinicians added steroids and continued the antituberculosis medication, and follow-up PET/CT showed complete resolution of these lesions. This case highlights the importance of recognizing paradoxical reactions to antituberculosis therapy, when restaging PET/CT reveals divergent findings, with some tumor foci responding and other lesions appearing to be progressing. Full article

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a cornerstone in minimally invasive thoracic lymph node sampling. In lung cancer staging, precise assessment of lymph node position is crucial for clinical decision-making. This study aimed to demonstrate a new deep learning method to classify thoracic lymph nodes based on their anatomical location using EBUS images. Bronchoscopists labeled lymph node stations in real-time according to the Mountain Dressler nomenclature. EBUS images were then used to train and test a deep neural network (DNN) model, with intraoperative labels as ground truth. In total, 28,134 EBUS images were acquired from 56 patients. The model achieved an overall classification accuracy of 59.5 ± 5.2%. The highest precision, sensitivity, and F1 score were observed in station 4L, 77.6 ± 13.1%, 77.6 ± 15.4%, and 77.6 ± 15.4%, respectively. The lowest precision, sensitivity, and F1 score were observed in station 10L. The average processing and prediction time for a sequence of ten images was 0.65 ± 0.04 s, demonstrating the feasibility of real-time applications. In conclusion, the new DNN-based model could be used to classify lymph node stations from EBUS images. The method performance was promising with a potential for clinical use. Full article

Sarcoidosis, a multi-organ system disease, often presents insidiously. Thrombocytopenia in sarcoidosis is frequent because of hypersplenism, granulomas infiltrating the bone marrow, or immune thrombocytopenia (ITP). The diagnosis of ITP relies on exclusionary criteria, given the absence of a definitive laboratory diagnostic feature. In the era prior to modern ITP management, sarcoidosis-associated ITP was known to manifest severely, often showing resistance to treatment and an increased risk of mortality. In this case, we present a young male who was admitted to a district hospital’s emergency room, displaying symptoms of hematuria, gingival bleeding, and a petechial rash. Blood tests revealed severe thrombocytopenia with a platelet count of 0, while all other metabolic and serological exams returned normal results. Infectious and autoimmune causes were ruled out, and a bone marrow examination excluded any hematological disorder. Initial management, including platelet transfusion and presumptive treatment for ITP with dexamethasone and Human Immunoglobulin IV (IVIG), failed to improve the patient’s platelet count or alleviate the hemorrhagic diathesis. Second-line therapy with Rituximab and Methylprednisolone was initiated with no benefit. Considering the hemorrhagic signs and the delayed response of Rituximab, we shifted to third-line therapy with Romiplostim at the maximal dose and continued Methylprednisolone. The platelet count recovered completely after the second Romiplostim administration (over 350 × 10⁹ platelets/L) and Methylprednisolone was rapidly tapered. To further study the causes of thrombocytopenia a total body CT scan was performed and it identified non-homogeneously hypodense tissue in the bilateral hilar area extending medially to the subcarinal area, suggesting possible lymphatic origin and raising suspicion of sarcoidosis. Further investigations, including Angiotensin Converting Enzyme (ACE) titration, bronchoscopy, bronchoalveolar lavage, and EndoBronchial UltraSound-guided TransBronchial Needle Aspiration (EBUS-TBNA), confirmed the diagnosis of sarcoidosis. Despite a mild restrictive insufficiency noted in spirometry, the patient remained asymptomatic with only a mild respiratory insufficiency, and hence, was enlisted for follow-up. As for the ITP, the platelet count remained normal over a year. Notably, while sarcoidosis onset often predates ITP onset by an average of 48 months, in our case the onset of the two diseases was simultaneously. Our case adds valuable information to the limited body of knowledge regarding the treatment of sarcoidosis-associated ITP. Full article

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often the only source of tumor tissue from patients with advanced, inoperable lung cancer. EBUS-TBNA aspirates are used for the diagnosis, staging, and genomic testing to inform therapy options. Here we extracted DNA and RNA from 220 EBUS-TBNA aspirates to evaluate their suitability for whole genome (WGS), whole exome (WES), and comprehensive panel sequencing. For a subset of 40 cases, the same nucleic acid extraction was sequenced using WGS, WES, and the TruSight Oncology 500 assay. Genomic features were compared between sequencing platforms and compared with those reported by clinical testing. A total of 204 aspirates (92.7%) had sufficient DNA (100 ng) for comprehensive panel sequencing, and 109 aspirates (49.5%) had sufficient material for WGS. Comprehensive sequencing platforms detected all seven clinically reported tier 1 actionable mutations, an additional three (7%) tier 1 mutations, six (15%) tier 2–3 mutations, and biomarkers of potential immunotherapy benefit (tumor mutation burden and microsatellite instability). As expected, WGS was more suited for the detection and discovery of emerging novel biomarkers of treatment response. WGS could be performed in half of all EBUS-TBNA aspirates, which points to the enormous potential of EBUS-TBNA as source material for large, well-curated discovery-based studies for novel and more effective predictors of treatment response. Comprehensive panel sequencing is possible in the vast majority of fresh EBUS-TBNA aspirates and enhances the detection of actionable mutations over current clinical testing. Full article

Background: Combined endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided tissue acquisition (EUS-TA) are accurate procedures for the diagnosis and staging of mediastinal lymph nodes (MLNs) in lung cancer. However, the respective contribution of separate and combined procedures in diagnosis and staging has not been fully studied. The aim of this study was to assess their respective performances. Methods: Patients with suspected malignant MLNs in lung cancer or recurrence identified by PET-CT who underwent combined EBUS-TBNA and EUS-TA were retrospectively reviewed. Results: A total of 141 patients underwent both procedures. Correct diagnosis was obtained in 82% with EBUS-TBNA, 91% with EUS-TA, and 94% with the combined procedure. The overall sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of EBUS-TBNA, EUS-TA, and the combined procedure for diagnosing malignancy were [75%, 100%, 100%, 58%], [87%, 100%, 100%, 75%], and [93%, 100%, 100%, 80%], respectively, with a significantly better sensitivity of the combined procedure (p < 0.0001). Staging (82/141 patients) was correctly assessed in 74% with EBUS-TBNA, 68% with EUS-TA, and 85% with the combined procedure. The overall sensitivity, specificity, PPV, and NPV of EBUS-TBNA, EUS-TA, and the combined procedure for lung cancer staging were [62%, 100%, 100%, 55%], [54%, 100%, 100%, 50%], and [79%, 100%, 100%, 68%], respectively, significantly better in terms of sensitivity for the combined procedure (p < 0.001). Conclusion: The combined EBUS-EUS approach in lung cancer patients showed better accuracy and sensitivity in diagnosis and staging when compared with EBUS-TBNA and EUS-TA alone. Full article

Introduction: Sarcoidosis is a multi-system granulomatous disease most commonly involving the lungs. It may be incidentally diagnosed during imaging studies for other conditions or non-specific symptoms. The appropriate follow-up of incidentally diagnosed asymptomatic stage 1 disease has not been well defined. Objective: To define the clinical course of incidentally diagnosed asymptomatic stage 1 sarcoidosis and propose an algorithm for the follow-up of these patients. Methodology: A retrospective case note analysis was performed of all EBUS-TBNA (endobronchial ultrasound-guided transbronchial needle aspiration)-confirmed cases of stage 1 sarcoidosis presenting incidentally to Bristol and Liverpool Interstitial Lung Disease services. Clinical history, serology results, imaging scans, and lung function parameters were examined at baseline, 12, and 24 months. A cost analysis was performed comparing the cost of the current 2-year follow-up guidance to a 1 year follow-up period. Results: Sixty-seven patients were identified as the final cohort. There was no significant change in the pulmonary function tests over the two-year follow-up period. Radiological disease stability was observed in the majority of patients (58%, n = 29), and disease regression was evidenced in 40% (n = 20) at 1 year. Where imaging was performed at 2 years, the majority (69.8%, n = 37) had radiological evidence of disease regression, and 30.2% (n = 16) showed radiological evidence of stability. All patients remained asymptomatic and did not require therapeutic intervention over the study period. Conclusions: Our results show that asymptomatic patients with incidental findings of thoracic lymph nodal non-caseating granulomas do not progress over a 2-year period. Our results suggest that the prolonged secondary-care follow-up of such patients may not be necessary. We propose that these patients are followed up for 1 year with a further year of patient-initiated follow-up (PIFU) prior to discharge. Full article

(1) Background: endobronchial ultrasound-guided mediastinal transbronchial cryo-node biopsy, previously assisted by fine-needle aspiration, is a novel technique of particular interest in the field of lung cancer diagnosis and is of great utility for extrathoracic tumor metastases, lymphomas, and granulomatous diseases. An integrated histological and molecular diagnosis of small samples implies additional difficulty for the pathologist. Additionally, emerging tumor biomarkers create the need to search for new approaches to better manage the tissue sample; (2) Methods: An analytical observational study of 32 mediastinal node cryobiopsies is carried out in 27 patients (n = 27). Statistical analysis using the t-student and Wilcoxon signed-rank tests for paired data is performed with SPSS 26 and R Statistical software. The significance level is established at p < 0.05; (3) Results: cryobiopsies were valid for diagnosis in 25 of 27 patients, with a maximum average size of 3.5 ± 0.7 mm. A total of 18 samples (66.67%) were positive for malignancy and 9 (33.33%) were benign. The tumor percentage measured in all neoplastic samples was greater than 30%. The average DNA and RNA extracted in nine non-small cell lung cancer cases was 97.2 ± 22.4 ng/µL and 26.6 ± 4.9 ng/µL, respectively; (4) Conclusions: the sample size obtained from an endobronchial ultrasound-guided mediastinal transbronchial cryo-node biopsy facilitates the morphological and histo-architectural assessment of inflammatory and neoplastic pathology. It optimizes molecular tests in the latter due to more tumor cells, DNA, and RNA. Full article

Lung cancer represents the second most common malignancy worldwide and lymph node (LN) involvement serves as a crucial prognostic factor for tailoring treatment approaches. Invasive methods, such as mediastinoscopy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), are employed for preoperative LN staging. Among the preoperative non-invasive diagnostic methods, computed tomography (CT) and, recently, positron emission tomography (PET)/CT with fluorine-18-fludeoxyglucose ([¹⁸F]FDG) are routinely recommended by several guidelines; however, they can both miss pathologically proven LN metastases, with an incidence up to 26% for patients staged with [¹⁸F]FDG PET/CT. These undetected metastases, known as occult LN metastases (OLMs), are usually cases of micro-metastasis or small LN metastasis (shortest radius below 10 mm). Hence, it is crucial to find novel approaches to increase their discovery rate. Radiomics is an emerging field that seeks to uncover and quantify the concealed information present in biomedical images by utilising machine or deep learning approaches. The extracted features can be integrated into predictive models, as numerous reports have emphasised their usefulness in the staging of lung cancer. However, there is a paucity of studies examining the detection of OLMs using quantitative features derived from images. Hence, the objective of this review was to investigate the potential application of PET- and/or CT-derived quantitative radiomic features for the identification of OLMs. Full article

Sedation techniques in interventional flexible bronchoscopy and endobronchial ultrasound-guided transbronchial-needle aspiration (EBUS-TBNA) are inconsistent and the evidence for required general anesthesia under full anesthesiologic involvement is scarce. Moreover, we faced the challenge of providing bronchoscopic care with limited personnel. Hence, we retrospectively identified 513 patients that underwent flexible interventional bronchoscopy and/or EBUS-TBNA out of our institution between January 2020 and August 2022 to evaluate our deep analgosedation approach based on pethidine/meperidine bolus plus continuous flow adjusted propofol, the bronchoscopist-directed continuous flow propofol based analgosedation (BDcfP) in a two-personnel setting. Consequently, 502 out of 513 patients received BDcfP for analgosedation. We identified cardiovascular comorbidities, chronic obstructive pulmonary disease, and arterial hypertension as risk factors for periprocedural hypotension. Propofol flow rate did not correlate with hypotension. Theodrenaline and cafedrine might be used to treat periprocedural hypotension. Moreover, midazolam might be used to support the sedative effect. In conclusion, BDcfP is a safe and feasible sedative approach during interventional flexible bronchoscopy and EBUS-TBNA. In general, after the implementation of safety measures, EBUS-TBNA and interventional flexible bronchoscopy via BDcfP might safely be performed even with limited personnel. Full article

Background. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic procedure for evaluating hilar and mediastinal lymphadenopathies and is the gold standard for lung cancer diagnosis and staging. Recent studies assessed the effectiveness of the 19-G flex needle in obtaining larger EBUS-TBNA samples, and prospective small series gave similar results in terms of diagnostic yield when testing different gauge needles. The lack of homogeneity between series and the small sample size of some prospective cohorts poses a limit to the validity of those results. This prospective controlled study compared the 19-G flex and 22-G needles in terms of diagnostic yield. An objective laboratory method was used to count cells and compare the two needles’ cytologic yields. Material. A prospective controlled study was conducted on 90 patients undergoing EBUS-TBNA for the diagnosis of hilar and mediastinal lymphadenopathies. The institutional ethic committee (IEO573) approved the study, and informed consent was obtained from all patients. Results. A total of 90 patients were enrolled in this study, 84.4% of whom were diagnosed with malignancy and 15.6% with non-neoplastic disease. Sensitivity for malignancy was 93.4% (CI: 87.4–97.1%) for the 19-G needle and 92.6% (CI: 86.3–96.5%) for the 22-G needle (p = 0.80). The percentage of malignant cells in the cell block was 63.9% and 61.5% for the 22-G and 19-G needles, respectively. The cell count assessed by flow cytometry was 2071 cells/µL (IQR: 600,2265) with the 22-G needle and 2761 cells/µL (IQR: 505,3250) with the 19-G needle (p = 0.79). The malignant cell count was 0.05 × 10³ cells/µL with the 22-G and 0.08 × 10³ cells/µL with the 19-G needle (p = 0.70). There was no difference in the presence of tissue cores in the samples, and rapid on-site evaluation (ROSE) cellularity was comparable between the two needles. Conclusions. The 19-G flex EBUS-TBNA needle is comparable to the 22-G needle in terms of diagnostic yield for cyto-histological evaluation of hilar and mediastinal lymphadenopathies. There is no difference between the 19-G and 22-G needle cell counts evaluated by flow cytometry. Full article

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and accurate diagnostic procedure used for investigating mediastinal pathologies. It is usually performed using an oral approach. The nasal route has been proposed but not extensively investigated. With the aim to report the use of linear EBUS through the nasal route and compare its accuracy and safety with the oral one, we conducted a retrospective analysis of the subjects who underwent an EBUS-TBNA procedure at our center. From January 2020 to December 2021, 464 subjects underwent an EBUS-TBNA, and in 417 patients, EBUS was performed through the nose or mouth. Nasal insertion of the EBUS bronchoscope was performed in 58.5% of the patients. No difference between the two insertion routes was observed in terms of location or number of stations sampled per subject. Procedure complications were mild and similar between the two groups (10.2% for the nasal group vs. 9.8% for the oral group). Minor epistaxis occurred in five subjects in the nasal group. Comparing the two groups, the rates of adequate specimens were similar (95.1% vs. 94.8%), as were the proportions of diagnostic specimens (84% vs. 82%). In conclusion, the nasal route for EBUS-TBNA is a valid alternative to the oral one. Full article

A 54-year-old woman on dialysis due to chronic renal failure had a fever lasting 2 weeks and was referred to a hospital. Non-enhanced CT and blood tests showed no remarkable findings. She was hospitalized and received an antibacterial drug. Although she was discharged after the fever subsided, she was hospitalized again due to a fever a few days later. A contrast-enhanced CT revealed mediastinal lymphadenopathy, and she was transferred to our hospital for a bronchoscopy. Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) for subcarinal lymph nodes was performed in our hospital. The Polymerase Chain Reaction (PCR) test of the obtained specimen was positive for mycobacterium tuberculosis, and histologically, caseous granulomas were found in the specimen. She was diagnosed with mediastinal tuberculous lymphadenitis, and HREZ (isoniazid, rifampicin, ethambutol, and pyrazinamide) treatment was started. The fever subsided immediately, and she was discharged from our hospital 2 weeks after the initiation of treatment. Thereafter, she received treatment as an outpatient. Since the use of a contrast medium was complicated by dialysis, a non-enhanced CT was performed at first, and it was difficult to make a diagnosis from this. We report this as an informative case that could be diagnosed with EBUS-TBNA, which was easily performed on a patient weakened by prolonged fever and dialysis. Full article