Utility of bronchoscopically obtained frozen cytology pellets for next-generation sequencing.

BACKGROUND: Next-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay. METHODS: We retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine. We investigated the amount of extracted DNA and RNA and determined the NGS success rates. We also compared the amount of DNA and RNA by bronchoscopy methods. To create the frozen cytology pellets, we first effectively collected the cells and then quickly centrifuged and cryopreserved them. RESULTS: A total of 132 patients were enrolled in this study between May 2016 and December 2022; of them, 75 were subjected to frozen cytology pellet examinations and 57 were subjected to frozen tissue examinations. The amount of DNA and RNA obtained by frozen cytology pellets was nearly equivalent to frozen tissues. Frozen cytology pellets collected by endobronchial ultrasound-guided transbronchial needle aspiration yielded significantly more DNA than those collected by transbronchial biopsy methods. (P < 0.01) In RNA content, cytology pellets were not inferior to frozen tissue. The success rate of NGS analysis with frozen cytology pellet specimens was comparable to the success rate of NGS analysis with frozen tissue specimens. CONCLUSIONS: Our study showed that frozen cytology pellets may have equivalent diagnostic value to frozen tissue for NGS analyses. Bronchial cytology specimens are usually used only for cytology, but NGS analysis is possible if enough cells are collected to create pellet specimens. In particular, the frozen cytology pellets obtained by endobronchial ultrasound-guided transbronchial needle aspiration yielded sufficient amounts of DNA. TRIAL REGISTRATION: This was registered with the University Medical Hospital Information Network in Japan (UMINCTR registration no. UMIN000052050).

Franseen needle in endobronchial ultrasound-guided transbronchial needle aspiration: a phase II prospective study.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been used to diagnose and stage lung cancer. Acquire™ Pulmonary and Expect™ Pulmonary dedicated EBUS-TBNA needles were introduced as the Franseen and Lancet needles, respectively. It is still unclear whether the Franseen or Lancet needles yield a higher quality specimen especially focusing on next-generation sequencing-based molecular testing. METHODS: A single-center, prospective study performed at the Chiba University Hospital randomly assigned patients to two groups: Group A, wherein the first and second EBUS-TBNA were performed using Lancet and Franseen needles, respectively, and Group B, wherein the first and second EBUS-TBNA were performed using Franseen and Lancet needles, respectively. Each specimen was compared and analyzed pathologically. The primary outcome was the histological tissue area except blood clot and the cellularity of each sample. We also examined the success rate of molecular testing. RESULTS: Twelve patients who underwent EBUS-TBNA between November 2022 and February 2023 were enrolled in this study. The tissue area of the specimens obtained by the Franseen and Lancet needles was 13.3 ± 6.4 mm2 and 10.6 ± 6.3 mm2, respectively (P = .355). The tumor cellularity in the specimens obtained using the Franseen and Lancet needles was 54.0 ± 30.3 and 46.2 ± 36.3%, respectively (P = .608). The success rate of molecular testing using the single-pass sample by Franseen needle was 85.7 and 57.1% by Lancet needle. No serious complications were reported. CONCLUSIONS: The Franseen needle tended to show a greater amount of specimen with higher tumor cellularity than the Lancet needle which may contribute higher success rate of molecular testing. Further studies must be conducted to validate the results of this study. KEY FINDINGS: What is known and what is new?  What is the implication, and what should change now?

Comparison of the specimen quality of endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized forceps versus mini forceps for lung cancer: A prospective study.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic procedure with adequate performance; however, its ability to provide specimens of sufficient quality and quantity for treatment decision-making in advanced-stage lung cancer may be limited, primarily due to blood contamination. The use of a 0.96-mm miniforceps biopsy (MFB) permits true histological sampling, but the resulting small specimens are unsuitable for the intended applications. Therefore, we introduced a 1.9-mm standard-sized forceps biopsy (SFB) and compared its utility to that of MFB. METHODS: We prospectively enrolled patients from three institutions who presented with hilar/mediastinal lymphadenopathy and suspected advanced-stage lung cancer, or those who were already diagnosed but required additional tissue specimens for biomarker analysis. Each patient underwent MFB followed by SFB three or four times through the tract created by TBNA using a 22-gauge needle on the same lymph node (LN). Two pathologists assessed the quality and size of each specimen using a virtual slide system, and diagnostic performance was compared between the MFB and SFB groups. RESULTS: Among the 60 enrolled patients, 70.0% were diagnosed with adenocarcinoma. The most frequently targeted sites were the lower paratracheal LNs, followed by the interlobar LNs. The diagnostic yields of TBNA, MFB and SFB were 91.7%, 93.3% and 96.7%, respectively. The sampling rate of high-quality specimens was significantly higher in the SFB group. Moreover, the mean specimen size for SFB was three times larger than for MFB. CONCLUSION: SFB is useful for obtaining sufficient qualitative and quantitative specimens.

EBUS-TBNA for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer clinically staged with PET/CT.

BACKGROUND AND OBJECTIVE: To evaluate the diagnostic accuracy and clinical usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer (NSCLC) clinically staged with positron emission tomography/computed tomography (PET/CT). METHODS: We conducted a study that included patients with centrally located T1N0M0 NSCLC, clinically staged with PET/CT who underwent EBUS-TBNA for mediastinal staging. Patients with negative EBUS-TBNA underwent mediastinoscopy, video-assisted mediastinoscopic lymphadenectomy (VAMLA) and/or lung resection with systematic nodal dissection, that were considered the gold standard. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), overall accuracy of EBUS-TBNA for diagnosing mediastinal metastases (N2 disease) and the number needed to treat (NNT: number of patients needed to undergo EBUS-TBNA to avoid a case of pathologic N2 disease after resection) were calculated. RESULTS: One-hundred eighteen patients were included. EBUS-TBNA proved N2 disease in four patients. In the remaining 114 patients who underwent mediastinoscopy, VAMLA and/or resection there were two cases of N2 (N2 prevalence 5.1%). The sensitivity, specificity, NPV, PPV and overall accuracy for diagnosing mediastinal metastases (N2 disease) were of 66%, 100%, 98%, 100% and 98%, respectively. The NNT was 31 (95% CI: 15-119). CONCLUSION: EBUS-TBNA in patients with central clinically staged T1N0M0 NSCLC presents a good diagnostic accuracy for mediastinal staging, even in a population with low prevalence of N2 disease. Therefore, its indication should be considered in the management of even these early lung cancers.

An International Survey of Practices in the Investigation and Endoscopic Treatment of Peripheral Pulmonary Lesions amongst Interventional Bronchoscopists.

INTRODUCTION: The investigation of peripheral pulmonary lesions (PPLs) can be challenging. Several bronchoscopic modalities have been developed to reach and biopsy PPL but the level of adoption of these techniques by interventional pulmonologists (IPs) is unknown. This international survey was conducted to describe current practices in PPL investigation among IP. METHODS: This survey was sent to all members of the World Association for Bronchology and Interventional Pulmonology, Canadian Thoracic Society Procedures Assembly, AABIP, and the Groupe d'Endoscopie Thoracique et Interventionnel Francophone. The survey was composed of 48 questions and three clinical cases to establish a portrait of modalities used to investigate and treat PPL by IP around the world. RESULTS: Three hundred and twelve IP responded to the survey. Most of them practice in Europe (n = 122), North America (n = 97), and Asia (n = 49). Half of responders perform more than 100 endoscopic procedures for PPL annually. General anesthesia and conscious sedation are used in similar proportions (53% and 47%, respectively). Rapid on site evaluation (ROSE) is used when sampling PPL by 42%. Radial EBUS (69%), fluoroscopy (55%), and electromagnetic navigation (27%) are the most widely used techniques. Most IP combine techniques (89%). Robotic bronchoscopy (15%) and cone-beam CT (8%) are almost exclusively used in the USA where, respectively, 60% and 37% of respondents reported using these modalities. Ten percent of IP currently had access to endoscopic treatment modalities for PPL. However, half of the remaining IP plan to acquire an endoscopic treatment modality in the next 2 years. CONCLUSION: Available techniques and practices worldwide vary significantly regarding PPL investigation and treatment.

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and Next Generation Sequencing Yields.

PURPOSE: The use of endobronchial ultrasound (EBUS) is standard practice for lung cancer diagnosis and staging. Next generation sequencing (NGS) for detection of genetic alterations is recommended in advanced, non-squamous, non-small-cell lung cancer (NSCLC). Existing protocols for NGS testing are minimal and reported yields vary. This study aimed to determine the yield of EBUS samples obtained for NGS using a sampling protocol at our institution and assess predictive factors to form collection protocols. METHODS: We reviewed EBUS bronchoscopies from 2016 to 2021 with non-squamous NSCLC diagnoses. For target lesions suspected to be malignant, the sampling protocol was: (a) two slides for on-site evaluation, (b) three to five fine needle aspirations rinsed into saline for immunohistochemical staining and in-house molecular markers, and (c) additional three to five rinses for NGS. Sufficiency for NGS processing was determined by the pathology department. RESULTS: Two hundred and seventy-eight non-squamous NSCLC samples were obtained by EBUS (205 adenocarcinoma; 73 not otherwise specified). EBUS was performed under general anesthesia in 75.5% of cases. The overall sample adequacy for NGS testing was 57.5%. Higher adequacy rates were observed when protocol was adhered to 66.0% versus 37.2% (p < 0.001). There was no statistically significant difference based on the size of the lesion or location of the sample. CONCLUSION: When a protocol of three to five dedicated needle rinses for NGS was followed, we nearly doubled our sample adequacy rate for NSG as compared to standard care. Studies are needed to determine the ideal collection and processing modality to preserve tissue samples for genetic sequencing.

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and PD-L1 Yields.

PURPOSE: Immunotherapy is a leading approach for treating advanced non-small cell lung cancer (NSCLC) by targeting the PD-1/PD-L1 checkpoint signaling pathway, particularly in tumors expressing high levels of PD-L1 (Jug et al. in J Am Soc Cytopathol 9:485-493, 2020; Perrotta et al. in Chest 158: 1230-1239, 2020). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method to obtain tissue for molecular studies, including PD-L1 analysis, in unresectable tumors (Genova et al. in Front Immunol 12: 799455, 2021; Wang et al. in Ann Oncol 29: 1417-1422, 2018). This study aimed to assess the adequacy of PD-L1 assessment in EBUS-TBNA cytology specimens. METHODS: Data was collected retrospectively from patients who underwent EBUS-TBNA between 2017 and 2021 for suspected lung cancer biopsy. Samples positive for NSCLC were examined for PD-L1 expression. EBUS was performed by experienced practitioners, following institutional guidelines of a minimum of five aspirations from positively identified lesions. Sample adequacy for molecular testing was determined by the pathology department. RESULTS: The analysis involved 387 NSCLC cases (149 squamous cell, 191 adenocarcinoma, 47 unspecified). Of the 263 EBUS-TBNA specimens tested for PD-L1, 237 (90.1%) were deemed adequate. While 84% adhered to the protocol, adherence did not yield better results. Significantly higher PD-L1 adequacy was observed in squamous cell carcinomas (93.2%) compared to adenocarcinoma (87.6%). The number of aspirations and sedation type did not correlate with PD-L1 adequacy in either cancer type, but lesion size and location had a significant impact in adenocarcinomas. Adenocarcinoma exhibited higher PD-L1 expression (68%) compared to squamous cell carcinoma (48%). CONCLUSION: EBUS-TBNA offers high yields for assessing immunotherapy markers like PD-L1, with satisfactory adequacy regardless of NSCLC subtype, lesion size, or location.

Diagnostic significance and cytological features of NUT carcinoma by EBUS-FNA, a case report and literature review.

Cytomorphological features of NUT carcinoma include sheets or discrete nests of primitive, monotonous, round to oval shaped tumour cells with high N/C ratio and brisk mitotic figures. Abrupt squamous differentiation might be a diagnostic hint. More than 50% positivity of NUT immunohistochemistry staining is diagnostic. NUT carcinoma represents a poorly differentiated malignancy by extremely aggressive clinical course and poor prognosis. It frequently manifests in midline organs, notably in the mediastinum and lung. The rising preferences for utilizing the EBUS-FNA procedure in diagnosing thoracic and lung lesions stems from its high diagnostic yield. Hence, recognizing the cytomorphological features of NUT carcinoma is crucial for timely treatment and improved patient survival.

Use of cytology fluid samples for predictive biomarker testing in lung cancer patients.

OBJECTIVE: To provide a method of directly using cytology fluid samples for predictive biomarker testing in lung cancer patients and to determine the efficacy of a variety of fluid sample types. METHOD: A review of our in-house data from a range of cytology samples including endobronchial ultrasound (EBUS) fine-needle aspirate (FNA) needle washings (NW) and serous effusions tested on the Biocartis Idylla platform. All fluid samples were originally tested using Sanger sequencing. RESULTS: Using our method for fluid samples all of our cytology samples tested for epithelial growth factor receptor (EGFR) yielded valid results on this platform and all variant cases identified. The data showed serous fluids provided the best quality DNA, and variant genotype reports were obtained within 150 minutes. CONCLUSION: Cytology fluid samples can be used for predictive biomarker testing for lung cancer patients to provide in-house results with all fluids providing good-quality DNA.

Rapid molecular profiling utilising minimal quantities of endobronchial ultrasound-guided aspirates for the detection of Epidermal Growth Factor Receptor, KRAS, ALK, ROS1, RET, NTRK and MET gene alterations from patients with non-small-cell lung carcinomas on the Biocartis Idylla™ platform.

OBJECTIVES: Comprehensive molecular analysis for patients with non-small-cell lung carcinoma (NSCLC) is essential for managing modern targeted therapies. This study sought to establish the feasibility of utilising real-time PCR to perform rapid and comprehensive profiling on minimal amounts of endobronchial ultrasound-guided (EBUS) aspirates as a fast, tissue-sparing route of predictive profiling. METHODS: A volume of 500 µL of EBUS aspirate and fixative from patients with NSCLC was decanted, and 80 µL (<1% of total specimen received) was utilised for analysis. Biocartis Idylla™ cartridges for epidermal growth factor receptor (EGFR) mutations, KRAS mutations and a GeneFusion cartridge (ALK, ROS1, RET, NTRK1/2/3 rearrangements & MET 14 exon skipping) were analysed for each case to provide molecular data on the main clinically relevant targets as per UK guidelines. RESULTS: A total of 62 cases were included; all of which had successful DNA analysis (EGFR and KRAS cartridges). RNA analysis (GeneFusion cartridge) was successful for 42 of 51 (82%) with initial approach, with 11 of 11 (100%) achieving a successful result with modified protocol. In all, 23 KRAS mutations (37%), 5 EGFR mutations (8%) and 1 ROS fusion (2%) were identified. Average time from specimen receipt to molecular read-out was 5 h. CONCLUSION: Real-time PCR utilising the Idylla™ platform is rapid, utilises minimal amounts of tissue and provides accurate results. We propose this is a useful ancillary method to utilise alongside next-generation sequencing (NGS) in cases of urgent clinical requirement or EBUS aspirates with inadequate quantities of tissue for NGS.

Impact of rapid on-site evaluation in expediting the fast investigative lung cancer pathway.

OBJECTIVE: EBUS-TBNA is a method of acquiring tissue samples from intrathoracic lymph nodes and central intrathoracic tumours in patients suspected of having lung cancer. Rapid on-site evaluation (ROSE) denotes assessing tissue samples during EBUS (or bronchoscopy), providing instant feedback on sample adequacy and provisional cytomorphological diagnosis. Sector multidisciplinary team (MDT) discussion can then make informed treatment decisions, with confirmatory immunohistochemistry being finalised before provision of final treatment. Currently, impact of ROSE on length of time patients spend on the lung cancer diagnostic pathway remains unclear. METHODS: We retrospectively evaluated the impact of ROSE on the length of time between patients' EBUS/bronchoscopy procedures and discussion at sector MDT, referred to as time to treatment decision (TTD), at our institution. Additionally, we assessed impact of ROSE on number of passes (number of times nodes/masses were sampled) per procedure. RESULTS: The mean TTD was 77.9% shorter (p = 0.001) with ROSE present than when absent. Patients who received ROSE spend 34.3% less time (p = 0.028) on lung cancer diagnostic pathway overall. There was a significant reduction in number of passes in non-malignant nodes with ROSE present (2.23) than when absent (3.14) (p < 0.001). With ROSE present there was a significantly greater number of passes at malignant sites (5.07) than non-malignant sites (2.23) (p < 0.001). CONCLUSIONS: These findings support conclusions made in our institution's previous study, that utilisation of ROSE reduces TTD. ROSE also allows safe advancement through nodes with low suspicion of malignant involvement, focusing time on sampling nodes/masses of greater suspicion.

Whole Genome Sequencing in Advanced Lung Cancer can be Performed Using Diff-Quik Cytology Smears Derived from Endobronchial Ultrasound, Transbronchial Needle Aspiration (EBUS TBNA).

INTRODUCTION: Maximising alternative sample types for genomics in advanced lung cancer is important because bronchoscopic samples may sometimes be insufficient for this purpose. Further, the clinical applications of comprehensive molecular analysis such as whole genome sequencing (WGS) are rapidly developing. Diff-Quik cytology smears from EBUS TBNA is an alternative source of DNA, but its feasibility for WGS has not been previously demonstrated. METHODS: Diff-Quik smears were collected along with research cell pellets. RESULTS: Tumour content of smears were compared to research cell pellets from 42 patients, which showed good correlation (Spearman correlation 0.85, P < 0.0001). A subset of eight smears underwent WGS, which presented similar mutation profiles to WGS of the matched cell pellet. DNA yield was predicted using a regression equation of the smears cytology features, which correctly predicted DNA yield > 1500 ng in 7 out of 8 smears. CONCLUSIONS: WGS of commonly collected Diff-Quik slides is feasible and their DNA yield can be predicted.

Cryobiopsy with radial-endobronchial ultrasound (Cryo-Radial) has comparable diagnostic yield with higher safety in comparison to computed tomography-guided transthoracic biopsy for peripheral pulmonary lesions: An exploratory randomised study.

BACKGROUND: Computed tomography-guided transthoracic biopsy (CT-TTB) is the 'gold standard' biopsy for lung nodules. Radial-endobronchial ultrasound (R-EBUS) bronchoscopy is another recommended biopsy but carries a lower diagnostic yield. Addition of cryobiopsy with R-EBUS (Cryo-Radial) has shown promising results. There are no studies comparing CT-TTB with Cryo-Radial biopsy. AIM: The co-primary aims were the diagnostic yeild and safety. The secondary aim: ability to test epidermal growth factor receptor (EGFR). METHODS: A randomised controlled, multicentre exploratory study was conducted at three tertiary hospitals. Patients with nodules >1 cm on CT of the chest were randomised to CT-TTB or Cryo-Radial. With Cryo-Radial, patients had 1-3 cryo-biopsies in addition to at least one R-EBUS biopsy through the 2.6 mm guide sheath. RESULTS: Forty-eight patients were randomised: 22 to CT-TTB and 26 to Cryo-Radial. Sixteen in the CT-TTB and 20 in the Cryo-Radial received the allocated biopsy. The diagnostic yield was CT-TTB 93.8% (15/16) versus Cryo-Radial 85% (17/20) P = 0.61 and the odds ratio was 0.37. For 5/13 (38%), a diagnosis was solely made on cryobiopsy. Eleven (78%) of 14 in CT-TTB versus 7/10 (70%) Cryo-Radial were suitable for EGFR testing P = 0.66, with odds ratio 0.63. Pneumothorax occurrence was 44% (7/16) in CT-TTB versus 4.2% (1/24) in Cryo-Radial. Two (12.5%) of 16 CT-TTB required chest drain insertion. CONCLUSION: Cryo-Radial is comparable in diagnostic yield and ability to perform EGFR testing with a significantly lower risk of pneumothorax, compared with CT-TTB. Cryo-Radial has the additional advantage of mediastinal staging during the same procedure with Linear-EBUS and is a promising first-line tool in the diagnostic method of lung cancer.

Clinical application of endobronchial ultrasonography-guided transbronchial needle aspiration biopsy-a single center, large sample, real-world study.

BACKGROUND: Endobronchial ultrasonography-guided transbronchial needle aspiration biopsy (EBUS-TBNA) has been used for more than 10 years in China. Its clinical application and diagnostic value in different diseases with large sample was lack of report. METHODS: A retrospective analysis was performed about the application and diagnostic value of EBUS-TBNA in different disease of patients in Respiratory Intervention Center of Guangzhou Institute of Respiratory Health from January 2012 to July 2020. RESULTS: A total 5758 patients were included with 182 patients excluded for lack of information. Finally, data of 5576 patients (3798 males and 1778 females) were analyzed. For anesthetize, most patients were undergoing general anesthesia of intravenous with spontaneous breathing (69.4%), followed by general anesthesia of intravenous and inhalation with tracheal intubation and mechanical ventilation (17.9%) and conscious sedation and analgesia (12.8%). Lymph nodes were the main sites of biopsy obtained (76.4%). Tumors accounted for the highest proportion of disease (66.4%), followed by infection diseases (9.9%), sarcoidosis (3.9%), lymphoma (1.1%), and others (18.7%). The sensitivity of EBUS-TBNA for diagnosis of tumor was 89.7%, and 40.8% for infection diseases. There were significant differences in the puncture site and proportions of diseases between male and females (both p < 0.05). Higher diagnostic value was found in male patients (p < 0.05). CONCLUSION: EBUS-TBNA has good diagnostic value for different mediastinal and central pulmonary space-occupying lesions diseases, with highest sensitivity for tumors. Higher diagnostic value was found in male patients.

The utility of WhatsApp-based off-site evaluation for rapid cytology of EBUS-TBNA samples.

BACKGROUND: Whether off-site evaluation of slides by a cytologist viewing the images shared by WhatsApp improves the on-site evaluation by a pulmonologist (P-ROSE) remains unknown. This study's objective was to compare the sensitivity of P-ROSE and WHOSE for adequacy and diagnosis of cytology specimens obtained by endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA). MATERIALS AND METHODS: We retrospectively reviewed our bronchoscopy database to identify subjects who underwent EBUS-TBNA for lymph node sampling and had reports of P-ROSE and WHOSE. We collected data on the adequacy of samples as reported by the pulmonologist (P-ROSE), remotely by the cytologist (WHOSE), and finally after detailed cytologic evaluation. The study's primary outcome was to assess the increment in sensitivity for adequacy and diagnostic category (using the final cytology report as reference) by incorporating WHOSE. RESULTS: We included 264 (P-ROSE, n = 184; WHOSE, n = 80) subjects. The sensitivity (95% CI) for sample adequacy by P-ROSE and WHOSE was 65.3% (57.9%-72%) and 92% (83.6%-96.2%), respectively. There was a 26.6% (95% CI, 16%-35.2%) increment in the sensitivity for adequacy. The sensitivity (95% CI) for diagnosis by P-ROSE and WHOSE was 53.9% (46%-61.1%) and 89.8% (79.5%-95.3%), respectively. There was a 35.9% (95% CI, 23.4%-45%) increment in the sensitivity for diagnosis with WHOSE. The agreement between P-ROSE and final cytology in adequacy was poor (κ = -0.023, p = 0.616). The agreement between WHOSE and final cytology was moderate for adequacy (κ = 0.491, p = <0.001). CONCLUSION: We found WHOSE significantly improves the performance of P-ROSE for rapid assessment of cytology specimens obtained by EBUS-TBNA.

Efficacy and safety of endosonography-guided transvascular needle aspiration of thoracic and abdominal lesions: A systematic review and meta-analysis.

BACKGROUND: The diagnosis of intrathoracic and abdominal masses is challenging when lesions are located behind major vessels. Endoscopic ultrasound (EUS) or endobronchial ultrasound (EBUS)-guided transvascular needle aspiration (TVNA) provides a potentially useful diagnostic tool for such lesions. Data with respect to the safety and outcome of E-TVNA are scarce. Hence, this meta-analysis was conducted to assess the critical role of E-TVNA for diagnosis of various lesions. METHODS AND MATERIAL: A meta-analysis was performed by pooling the data from studies obtained from comprehensive search of Medline, Embase, and Scopus from January 2000 to September 2022. The outcomes analyzed included sample adequacy, diagnostic accuracy and adverse events including bleeding. RESULTS: A total of 17 studies (n = 411) were included in the final analysis. The pooled rate of sample adequacy was 91.5% [95% confidence interval (CI): 86.8-96.2], while the pooled rate of diagnostic accuracy was 85.0% (95% CI: 78.9-91.2). The pooled rate of bleeding with E-TVNA was 1.4% (95% CI 0.0-3.1%). All the episodes of bleeding were mild and resolved without any further intervention. There was no significant heterogeneity with respect to various outcomes and results were comparable on sensitivity analysis. CONCLUSIONS: E-TVNA offers a safe and accurate diagnostic modality for the diagnosis of mediastinal and abdominal lesions located on the other side of major vessels. Selection of potential candidates and close periprocedural observation are essential to improve the outcome.

A Case of Mediastinal Tuberculous Lymphadenitis in a Chronic Dialysis Patient Diagnosed by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA).

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.

[Transbronchial cryobiopsy for mediastinal lesions: a pilot study]. / Transbronkhial'naya kriobiopsiya limfouzlov i novoobrazovanii sredosteniya: pilotnoe issledovanie.

OBJECTIVE: To describe a novel transbronchial cryobiopsy technique for mediastinal lesions after initial ultrasound assessment and EBUS-TBNA. MATERIAL AND METHODS: Transbronchial cryobiopsy (TBCB) was performed in 35 patients with suspicious mediastinal lesions between November 2020 and September 2022. Age of patients ranged from 22 to 75 years (median 50 [39; 62]). Men-to-women ratio was 13:22. RESULTS: According to morphological data, patients with sarcoidosis (n=13), NSCLC (n=7) and metastases of other tumors (n=3) prevailed. There were patients with B-cell lymphoma (n=1), Castleman disease (n=1) and small cell lung cancer (n=2). Among 15 biopsies for immunohistochemical examination, samples were sufficient for final morphological conclusion in 11 (73.3%) cases (95% CI 48.5-89.1). In 4 (11.4%) cases (95% CI 4.5-26), examination was uninformative. Repeated biopsy was performed in 2 cases, and sarcoidosis of thoracic lymph nodes was confirmed. Sensitivity, specificity and accuracy of transbronchial cryobiopsy were 93.3, 100 and 94%, respectively. There were no clinically significant complications. In one case, chest X-ray revealed pneumomediastinum without need for additional treatment. CONCLUSION: Transbronchial mediastinal cryobiopsy is a perspective method for diagnosis of mediastinal neoplasms. Apparently, this approach may be advisable in patients with suspected sarcoidosis or lymphoproliferative diseases.

Effect of chlorhexidine Mouthrinse on prevention of microbial contamination during EBUS-TBNA: a randomized controlled trial.

BACKGROUND: Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure, fatal infectious complications have been reported. However, adequate preventive strategies have not been determined. We aimed to investigate the effect of chlorhexidine mouthrinse on the prevention of microbial contamination during EBUS-TBNA. METHODS: In this single-center, assessor-blinded, parallel-group randomized controlled trial, we randomly assigned adult participants undergoing EBUS-TBNA using a convex probe to gargle for 1 minute with 100 mL of 0.12% chlorhexidine gluconate before EBUS-TBNA or to receive usual care (no chlorhexidine mouthrinse). Aspiration needle wash samples were collected immediately after completion of EBUS-TBNA by instilling sterile saline into the used needle. The primary outcome was colony forming unit (CFU) counts per mL of needle wash samples in aerobic cultures. Secondary outcomes were CFU counts per mL of needle wash samples in anaerobic cultures, fever within 24 hours after EBUS-TBNA, and infectious complications within 4 weeks after EBUS-TBNA. RESULTS: From January 2021 to June 2021, 106 patients received either chlorhexidine mouthrinse (n = 51) or usual care (n = 55). The median CFU counts of needle wash samples in aerobic cultures were not significantly different in the two groups (10 CFU/mL vs 20 CFU/mL; P = 0.70). There were no significant differences between the groups regarding secondary outcomes, including median CFU counts in anaerobic cultures (P = 0.41) and fever within 24 hours after EBUS-TBNA (11.8% vs 5.6%, P = 0.31). There were no infectious complications within 4 weeks in both groups. CONCLUSIONS: Chlorhexidine mouthrinse did not reduce CFU counts in needle wash samples of EBUS-TBNA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04718922 . Registered on 22/01/2021.

Endoscopic nodal staging in oligometastatic non-small cell lung cancer (NSCLC) being treated with stereotactic ablative radiotherapy (ENDO-SABR).

BACKGROUND: Research in treatment of non-small cell lung cancer (NSCLC) has shown promising results with stereotactic ablative radiotherapy (SABR) of oligometastatic disease, wherein distant disease may be limited to one or a few distant organs by host factors. Traditionally, PET/CT has been used in detecting metastatic disease and avoiding futile surgical intervention, however, sensitivity and specificity is limited to only 81 and 79%, respectively. Mediastinal staging still identifies occult nodal disease in up to 20% of NSCLC patients initially thought to be operative candidates. Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive tool for the staging and diagnosis of thoracic malignancy. When EBUS is combined with endoscopic ultrasound using the same bronchoscope (EUS-B), the diagnostic sensitivity and negative predictive value increase to 84 and 97%, respectively. Endoscopic staging in patients with advanced disease has never been studied, but may inform treatment if a curative SABR approach is being taken. METHODS: This is a multi-centre, prospective, cohort study with two-stage design. In the first stage, 10 patients with oligometastatic NSCLC (lung tumour ± hilar/mediastinal lymphadenopathy) with up to 5 synchronous metastases will be enrolled An additional 19 patients will be enrolled in the second stage if rate of treatment change is greater than 10% in the first stage. Patients will be subject to EBUS or combined modality EBUS/EUS-B to assess bilateral lymph node stations using a N3 to N2 to N1 progression. Primary endpoint is defined as the rate of change to treatment plan including change from SABR to conventional dose radiation, change in mediastinal radiation field, and change from curative to palliative intent treatment. DISCUSSION: If a curative approach with SABR for oligometastatic disease is being explored, invasive mediastinal staging may guide treatment and prognosis. This study will provide insight into the use of endoscopic mediastinal staging in determining changes in treatment plan of NSCLC. Results will inform the design of future phase II trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04852588. Date of registration: April 19, 2021. PROTOCOL VERSION: 1.1 on December 9, 2021.