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Introduction Endobronchial ultrasound (EBUS) bronchoscopes have been used mainly through the airway for EBUS-guided transbronchial needle aspiration (EBUS-TBNA); however, they can also be used through the esophagus. The esophageal approach, endoscopic ultrasound with bronchoscope-guided fine needle aspiration (EUS-B-FNA), has gradually become popular, as it can evaluate lesions that cannot be accessed through the airway. Purpose This study aimed to evaluate the value of adding EUS-B-FNA to EBUS-TBNA performed by pulmonologists for intrathoracic lesions in the clinical setting. Methods Between March 2009 and March 2020, all patients who underwent EUS-B-FNA and EBUS-TBNA for diagnostic purposes were included and retrospectively analyzed at a single institution. Results A total of 1794 procedures using an EBUS bronchoscope including, EBUS-TBNA, EUS-B-FNA, and the combination of EBUS-TBNA and EUS-B-FNA for evaluating intrathoracic lesions, were performed. We finally analyzed 276 patients who underwent EUS-B-FNA for diagnostic purposes. EUS-B-FNA provided diagnostic materials from only EBUS-TBNA-inaccessible lesions in 26 patients and in 18 patients whose conditions were inappropriate for bronchoscopy (e.g., respiratory failure, airway stenosis, etc.). EUS-B-FNA provided diagnostic results in four patients with non-diagnostic EBUS-TBNA results. EUS-B-FNA was preferable to EBUS-TBNA in 4.4% (48 of 1091) of patients; therefore, adding EUS-B-FNA to EBUS-TBNA increased the diagnostic yield from 72.6% (1043 of 1437) to 75.9% (1091 of 1437). Conclusion Pulmonologists are able to enhance diagnostic yields by acquiring the EUS-B-FNA technique.

Background IgG4-related disease is a systemic fibroinflammatory disease that is mainly seen in older men, and involves multiple organs, such as the pancreas and lungs. However, 75% of patients with IgG4-related lung disease are asymptomatic (if they are symptomatic, they mainly complain of nasal congestion, rhinorrhoea, chest pain, and cough) and are incidentally diagnosed through chest computed tomograph. Although, nodules in the airway and bronchial wall thickening are criteria for diagnosis, it is important that nodules have been reported in peripheral airways in several cases and rarely in the central airway. Case presentation A 74-year-old woman previously diagnosed with Mikulicz’s disease presented with swelling of the eyelid margin on both sides and visual disturbances. Computed tomography revealed extensive multiple nodules and mucosal oedema of the trachea and both bronchi. On flexible bronchoscopy under local anaesthesia, extensive lesions were observed from the middle of the trachea to the carina, extending into both segmental bronchi. The nodules were continuous with the normal respiratory tract mucosa, and the surfaces were smooth with minimal neovascularisation. Due to the solid nature of the lesion, obtaining an adequate amount of specimen was challenging. Therefore, we used a 1.9 mm cryoprobe under intubation, resulting in minimal bleeding. Subsequently, the patient was diagnosed with IgG4-related lung disease. Conclusions The present case is very rare because of the presence of multiple nodules, severe mucosal edema of the central airway and the absence of mediastinal lymphadenopathy, ground glass nodules, and lung masses. Therefore, it is important to consider differential diagnoses. Thus, we emphasise the importance of endobronchial cryobiopsy for obtaining an adequate number of tissue specimens in such cases to establish a definitive pathological diagnosis.

Background There are no prospective studies to estimate whether cytology specimens can replace tissue samples using lung cancer gene panel analysis. We evaluated the success rate of gene panel testing and nucleic acid yield and quality when using cytology specimens for lung cancer over tissue specimens. Methods In this prospective study, clinical cytology specimens collected via transbronchial brushing, needle aspiration washing, and pleural effusion were stored in a nucleic acid stabilizer. The primary endpoint was the superior success rate of gene analysis using cytology specimens over the conventional success rate using tissue specimens. Results The full analysis set included 248 cases. The success rate for gene panel analysis using cytology specimens was 98.4% (95% confidence interval (CI), 95.9–99.6%) with a positive concordance rate of 97.3% (95% CI, 90.7–99.7%) by other companion diagnostic kits. The median value for nucleic acid yield and quality (DNA/RNA integrated number) of cytology specimens was 546.0/426.5 ng and 9.2/4.7 for DNA/RNA, respectively. The Pearson correlation coefficient of variant allele frequency between tissue formalin-fixed and paraffin-embedded (FFPE) sample and cytology specimens for mutant cases was 0.815. The ratio of double-stranded to total DNA showed that cytology specimens were of significantly higher quality than FFPE specimens. Conclusions The success rate of cytology specimens in gene analysis was significantly higher than conventional data. Because of the sufficient nucleic acid yield, high quality, and high correlation of mutant allele frequency compared to FFPE specimens, cytology specimens are suitable for panel testing as tissue substitutes. Trial registration UMIN Registry UMIN000047215 (cPANEL trial).  https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053766 .

Background: The silicone Y-stent has mainly been used for the treatment of lesions around the main carina, and only a few case reports have been published on the technique for the lesions around the secondary left carina (LC2). Objectives: We investigated the feasibility, efficacy and safety of a stenting technique using a silicone Y-stent for patients with airway stenosis around LC2. Methods: Patients who underwent airway stent placement between December 2010 and September 2014 in a single center were retrospectively reviewed. Under general anesthesia, using rigid and flexible bronchoscopes, the airway lumen was re-established followed by Y-stent placement on LC2. Results: We performed 274 airway stenting procedures for 253 patients during the study period. Twelve of them (7 with lung cancer, 3 with esophageal cancer/carcinosarcoma, 1 with thyroid cancer and 1 with renal cancer) underwent a Y-stent placement on LC2. Respiratory symptoms were relieved in all patients. Six of 7 patients with supplemental oxygen, including the mechanically ventilated patient before stent placement, could be discharged without supplemental oxygen. The chest radiograph after the procedure showed increased lung volume in all 7 patients with partial or complete atelectasis. Median survival after stenting was 197 days at the time of data collection. Retention of secretions occurred in 1 and hemoptysis in another patient. Conclusions: Silicone Y-stent placement on LC2 is technically feasible, effective and acceptably safe.

Background: Although rapid on-site cytologic evaluation (ROSE) is widely used during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), its role remains unclear. Objectives: The purpose of the present study was to evaluate the efficacy of ROSE during EBUS-TBNA in the diagnosis of lung cancer. Methods: One hundred and twenty patients highly suspected of having lung cancer who had hilar/mediastinal lymphadenopathy or a tumor adjacent to the central airway were enrolled in this study and randomized to undergo EBUS-TBNA with or without ROSE. Results: Twelve patients with visible endobronchial lesions were excluded in the analysis. Thus, a total of 108 patients (55 in the ROSE group, 53 in the non-ROSE group) were analyzed. Additional procedures including EBUS-TBNA for lesions other than the main target lesion and/or transbronchial biopsy in the same setting were performed in 11% of patients in the ROSE group and 57% in the non-ROSE group (p < 0.001). Mean puncture number was significantly lower in the ROSE group (2.2 vs. 3.1 punctures, p < 0.001), and mean bronchoscopy time was similar between both groups (22.3 vs. 22.1 min, p = 0.95). The sensitivity and accuracy for diagnosing lung cancer were 88 and 89% in the ROSE group, and 86 and 89% in the non-ROSE group, respectively. No complications were associated with the procedures. Conclusions: ROSE during EBUS-TBNA is associated with a significantly lower need for additional bronchoscopic procedures and puncture number.

BackgroundPD-L1 expression on tumor cells is a marker of PD-1/PD-L1 antibody treatment efficacy for advanced non-small cell lung cancer (NSCLC). PD-L1 antibody (atezolizumab) prolongs overall survival (OS) compared with platinum doublet as first-line treatment for NSCLC with high PD-L1 expression. Bevacizumab enhanced cytotoxic agent and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor efficacy in non-squamous (NS)-NSCLC, and PD-1/PD-L1 antibodies in preclinical models.MethodsThis single-arm phase II study investigated clinical benefits of adding bevacizumab 15 mg/kg to atezolizumab 1200 mg fixed dose in a first-line setting for advanced NS-NSCLC patients with PD-L1 expression ≥50% without EGFR/ALK/ROS1 alterations. Primary endpoint was objective response rate (ORR) assessed by central review committee. Secondary endpoints were progression-free survival (PFS), duration of response (DOR), OS, and safety.ResultsOf 39 enrolled patients, 33 (84.6%) had stage IV NSCLC and 36 (92.3%) had smoking history. As of March 31, 2020, no patient had a complete response and 25 patients had a partial response (ORR=64.1%, 95% CI 47.18 to 78.80). Twelve-month PFS and OS rates were 54.9% (35.65 to 70.60) and 70.6% (50.53 to 83.74), respectively. The median DOR in 25 responders was 10.4 months (4.63–not reached). The median treatment cycle was 12 (1 to 27). Nineteen patients discontinued study treatment because of disease progression (N=17) or immune-related adverse events (AEs) (N=2) (sclerosing cholangitis or encephalopathy). There were 23 serious AEs in 12 patients, but no grade 4/5 toxicity.ConclusionsAtezolizumab with bevacizumab is a potential treatment for NS-NSCLC with high PD-L1 expression.Trial registration numberJapicCTI-184038.

Background: Airway stenting is an alternative therapy for patients with complicated esophagectomy. Case presentation: A 60-year-old man with clinical stage IIIA esophageal cancer underwent neoadjuvant chemotherapy followed by robot-assisted subtotal esophagectomy with cervical esophagogastrostomy and jejunostomy. During surgery, both bronchial arteries were ligated to facilitate esophageal mobilization. Bronchoscopy on the first postoperative day showed no abnormalities; however, by the second postoperative day, the patient developed pneumonia and septic shock, requiring mechanical ventilation. On the fifth postoperative day, bronchoscopy revealed extensive epithelial injury extending from the trachea to both main bronchi, indicating ischemic airway damage. He was diagnosed with airway necrosis and referred to our respiratory department. Serial bronchoscopic examinations and suctioning of the sloughed epithelium were performed, and a tracheostomy enabled weaning from mechanical ventilation. By the twenty-fourth postoperative day, bronchoscopy revealed the accumulation of large, hardened secretions within the trachea, carina, and both main bronchi, resulting in airway narrowing and a high risk of asphyxiation. A silicone Y-shaped airway stent was inserted to maintain patency. Following stent placement, airway secretions progressively decreased, and the patient was discharged on the sixty-third postoperative day. The stent was removed six months later, with no recurrence of airway or respiratory complications. Conclusion: This case illustrates a rare but severe complication of extensive airway necrosis, likely caused by intraoperative bronchial artery ligation and dissection of the tracheal membranous portion. Although preservation of the bronchial arteries and meticulous surgical technique are essential preventive strategies, such complications may be unavoidable. In cases of extensive airway necrosis, airway stenting can serve as an effective therapeutic option to prevent obstruction and support recovery.

Background/Aim For patients treated with osimertinib as first-line therapy, there have been no studies comparing both progression-free survival (PFS) and overall survival (OS) according to performance status (PS). Furthermore, no studies have examined differences in baseline genetic abnormalities between patients with poor and good PS. Therefore, we aimed to investigate differences in baseline genetic abnormalities and treatment effects between patients with poor and good PS who received osimertinib as the primary treatment. Patients and methods This is a secondary analysis of the ELUCIDATOR study, which is a multi-center prospective observational study in Japan that assessed mechanisms underlying resistance to osimertinib as first-line treatment for advanced non-small cell lung cancer with epidermal growth factor receptor mutations. Results There were 153 and 25 patients in the good and poor PS groups, respectively. Multivariate analysis revealed no significant between-group differences in PFS (hazards ratio [HR]: 0.98, 95% confidence interval [CI]: 0.52–1.72, p  = 0.946). Multivariate analysis of OS revealed that poor PS was a poor prognostic factor (HR: 2.67, 95% CI: 1.43–4.73, p  = 0.003). Regarding baseline genetic abnormalities, there was a significant increase in APC-positive cases (20.0% vs. 2.2%, p  = 0.009) and a trend toward more CTNNB1-positive cases in the poor PS group than in the good PS group (14.3% vs. 2.9%, p  = 0.062). Conclusion There was no between-group difference in PFS, although OS was significantly inferior in the poor PS group. Additionally, there was a significant increase in APC-positive cases and a trend toward more CTNNB1-positive cases in the poor PS group.

BackgroundSince the overall survival (OS) of patients enrolled in the first clinical phase III trial (WJOG5108L) was not recorded owing to time constraints, the present study (WJOG5108LFS) with a longer follow-up (66.6 months) aimed to compare OS of those treated with erlotinib (ER) and gefitinib (GE) for lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation.MethodsAmong 536 enrolled patients, 362 (67.5%) were EGFR mutation-positive, including 182 in the ER arm and 180 in the GE arm. Median survival time (MST) and progression-free survival (PFS) were calculated using Kaplan–Meier survival curves. OS and PFS were determined for patients with EGFR mutation.ResultsMSTs of ER (n = 182) and GE arms (n = 180) were 31.97 and 27.98 months, respectively (P = 0.3573, hazard ratio = 1.116). MSTs of exon 19 mutation patients in ER (n = 99) and GE arms (n = 89) were 37.49 and 28.91 months, respectively (P = 0.3791). MSTs of L858 mutation patients in ER (n = 82) and GE arms (n = 89) were 22.98 and 27.79 months, respectively (P = 0.7836). In patients with brain metastasis harboring mutation, response rates were 32.8% and 22.2% (P = 0.160), MSTs were 23.46 and 23.89 months (P = 0.7410), and PFS were 9.49 and 6.98 months (P = 0.1481) in the ER (n = 67) and GE arms (n = 72), respectively.ConclusionsNo significant differences in OS were observed between the ER and GE arms in all patients with EGFR mutation and those with brain metastasis harboring EGFR mutation.

Background: While endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used as an initial diagnostic procedure for pathological confirmation of sarcoidosis, it is unclear how many passes are required to obtain diagnostic materials. Objectives: The aim of this study was to determine the number of needle passes needed for the diagnosis of stage I/II sarcoidosis using EBUS-TBNA. Methods: At three institutions, 109 patients with suspected stage I/II sarcoidosis were recruited and underwent 6 passes of EBUS-TBNA for the main target lesion. Additional EBUS-TBNA for other lesions was permitted. The cumulative yields of needle passes for detecting noncaseating epithelioid cell granulomas were analyzed. Results: A total of 109 patients underwent EBUS-TBNA for 184 lesions. EBUS-TBNA identified specimens containing granulomas in 81 of 92 patients (88%) with a final diagnosis of sarcoidosis. The cumulative yields through the first, second, third, fourth, fifth, and sixth passes for the main target lesion were 63, 75, 82, 85, 86 and 88%, respectively. In the 55 patients that underwent EBUS-TBNA for multiple lesions, the cumulative yields of 2 passes per lesion for 2 lesions (total of 4 passes) and of 4 passes for single lesions were 86 and 84%, respectively (p = 1.00). Conclusions: If rapid on-site cytological evaluation is not available, we recommend at least 4 passes per patient for either single or multiple lesions with EBUS-TBNA for pathological diagnosis of stage I/II sarcoidosis.