Feasibility and accuracy of rapid on-site evaluation of touch imprint cytology during transbronchial biopsy.

BACKGROUND: Rapid on-site evaluation (ROSE) of cytologic material is widely performed because it provides clinicians with instant diagnostic information. However, the utility of ROSE of touch imprint cytology (ROSE-TIC) during transbronchial biopsy (TBB) remains unclear. The aim of this study was to evaluate the feasibility and accuracy of ROSE-TIC for TBB. METHODS: A retrospective study was performed on patients who underwent diagnostic bronchoscopy combined with ROSE-TIC. The results of ROSE-TIC, diagnosed as either positive or negative for malignancy, were compared with the histological findings and final diagnosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated. The success rate of molecular testing on TBB specimens was also assessed. RESULTS: Overall, 460 patients underwent bronchoscopy with ROSE-TIC. Of these, 377 cases (82.0%) were malignant and 83 cases (18.0%) were non-malignant in the final diagnosis. Compared with the histological findings, ROSE-TIC showed sensitivity, specificity, PPV, NPV, and diagnostic accuracy values of 91.1%, 90.4%, 94.8%, 84.0%, and 90.9%, respectively. Compared with the final diagnosis, ROSE-TIC showed sensitivity, specificity, PPV, NPV, and diagnostic accuracy values of 75.3%, 91.6%, 97.6%, 45.0%, and 78.3%, respectively. Seven discordant cases (1.5%) were positive on ROSE-TIC and negative on final diagnosis. The success rates for molecular analysis from TBB samples were 96.6% for EGFR mutation, 87.3% for ALK rearrangement, 93.1% for ROS1 rearrangement, and 96.2% for PD-L1 expression. CONCLUSIONS: The accuracy of ROSE-TIC is high. It can be useful for obtaining instant diagnosis, contributing to a high success rate of molecular analysis for targeted therapy.

Specimen acquisition training with a new biosimulator in endobronchial ultrasound-guided transbronchial needle aspiration.

Training for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has focused on the procedure itself; however, the techniques for obtaining adequate sample are also important for achieving a pathological diagnosis as well as for molecular testing. The aim of this study was to evaluate the feasibility and efficacy of a biosimulator for training subjects in adequate sample acquisition during EBUS-TBNA.A total of 19 bronchoscopists voluntarily participated in this study. A biosimulator (ArtiCHEST, HARADA Corporation, Tokyo, Japan) was used for the training. After a 10-minute briefing, the first pass was performed by pairs of trainees. The trainees then received a 30-minute lecture that focused on the acquisition of samples using EBUS-TBNA. The trainees next performed their second pass under the supervision of the trainers. Each participant obtained a cytological smear that was coded and evaluated for quantity as well as quality by an independent cytotechnologist.The trainees had an average of 5.9 years of bronchoscopy experience. With regard to the quantity evaluation, 9 (47.4%) subjects sampled a greater number of lymphocytes on the second pass than on the first, whereas 2 were better on the first pass, and the others sampled roughly the same amount both times. With regard to the quality assessment, 9 (47.4%) subjects obtained better quality samples on the second pass, whereas the quality of the first and second pass was deemed to be roughly the same for the remaining subjects.A biosimulator can be used to train doctors in specimen acquisition and evaluate their skills with sampling using EBUS-TBNA.

Transbronchial biopsy needle rinse solution used for comprehensive biomarker testing in patients with lung cancer.

INTRODUCTION: Although genetic information is essential for molecular targeted therapy for personalized medicine, tissue sampling for genetic analysis remains challenging. We investigated the utility of bronchoscopic sampling in non-small-cell lung cancer (NSCLC) patients compared with conventional histological materials for multiple genetic analyses. METHODS: Patients with NSCLC proven by onsite cytological evaluation during bronchoscopic survey were eligible for this study. After conventional needle aspiration biopsy by flexible bronchofiberscopy of primary lesions or convex-probe endobronchial ultrasound of lymph nodes, the used needle was rinsed with saline, and the ultra-microsample (uMS) was used for cytological diagnosis and genetic analysis. Gene mutations and fusion genes were examined by high-resolution melting analysis and direct sequencing. The results from the uMS and those from conventional histological samples were compared. RESULTS: A total of 134 lesions (48 primary and 86 metastatic) were analyzed. Adenocarcinoma (n = 80), squamous-cell carcinoma (n = 43), and NSCLC (n = 11) samples were pathologically confirmed in histological cores; however, malignancies were detected in only 45 (34%) of the corresponding uMS. In 62 samples, genetic disorders, including epidermal growth factor receptor (n = 21), K-ras (n = 11), and BRAF mutations (n = 1); anaplastic lymphoma kinase (n = 5), receptor tyrosine kinase (n = 1), and RET fusion genes (n = 1); and silent mutations (n = 22), were identified. In total, 1474 molecular tests were performed, and 1464 tests (99.3%) were identical for both histological samples and uMS. CONCLUSION: Bronchoscopic uMS (biopsy needle rinsed fluids) are useful for multiple genetic examinations in NSCLC.

Rapid on-site cytologic evaluation during endobronchial ultrasound-guided transbronchial needle aspiration for nodal staging in patients with lung cancer.

BACKGROUND: The utility of rapid on-site evaluation (ROSE) during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging in lung cancer is still controversial. The aim of this study was to assess the role of ROSE during EBUS-TBNA and the interpretation of its results. METHODS: We performed a retrospective chart review of patients with suspected or diagnosed lung cancer who underwent EBUS-TBNA for lymph node staging. The slides were air-dried and Diff-Quik (American Scientific Products, McGaw Park, IL) staining was used for ROSE. Additional smears were prepared for Papanicolaou staining and any remaining sample was placed in 10% formalin for histologic evaluation. The results of ROSE were compared with the results of the final pathologic diagnosis. RESULTS: EBUS-TBNA was performed in 438 patients on 965 lymph nodes. Eighty-four lymph nodes (8.7%) were determined insufficient for definitive diagnosis by final cytologic evaluation. However 45 of the 84 lymph nodes were able to be diagnosed by histologic examination. The non-diagnostic sampling rate was 4.0%. There were no false-positive results on ROSE; however 25 cases (5.7%) were falsely evaluated as negative on ROSE. The concordance rate for staging between ROSE and final pathologic diagnosis was 94.3%. The sensitivity, specificity, negative predictive value, and diagnostic accuracy rate of EBUS-TBNA for correct lymph node staging was 96.5%, 100%, 89.8%, and 98.2%, respectively. CONCLUSIONS: ROSE during EBUS-TBNA for material adequacy showed a low rate of non-diagnostic sampling. There was a high agreement between the on-site and final pathologic evaluation during EBUS-TBNA; however immediate diagnosis should be approached with caution.

Evaluation of a learning system for endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an established modality for nodal staging in lung cancer; nevertheless, acquisition on effective fiberscope handling and puncture techniques remains challenging. Here, we present a novel EBUS-TBNA learning system protocol and evaluate the ability of physicians trained using this protocol to perform cytological diagnosis and histological sampling. MATERIAL AND METHODS: We designed a 5-step learning system as follows: (1) preparation, (2) probe insertion, (3) sonographic observation, (4) TBNA assistant, and (5) TBNA operator. Each trainee must accomplish the first 4 steps before beginning step 5. In step 5, EBUS-TBNA was performed in tandem by the trainee and supervisor. Diagnostic accuracy and success of histological sampling were recorded for each trial; results of the corresponding supervisor served as a control. RESULTS: All 11 trainees entered step 5 after completing steps 1-4 over 5-10 trials. A total of 308 nodes were punctured in step 5. The overall accuracy of cytological diagnosis was 91.2% among trainees, and the histological sampling success rate was 85.4%. The diagnostic accuracy increased from 85.4% to 93.9% (p = 0.027) after 12 needle aspiration experiences. The sizes of nodes associated with success and failure were 13.6 and 11.1mm (p = 0.001), respectively. CONCLUSIONS: Our EBUS-TBNA learning system provided a satisfactory educational pathway for trainees and can be used to improve accessibility of EBUS-TBNA.

Cytological findings of pre-invasive bronchial lesions detected by light-induced fluorescence endoscopy in a lung cancer screening system.

Lung cancer is a global epidemic and the number one cause of death among all cancers, with a very high morbidity. A new strategy for the treatment of lung cancer is the detection and eradication of pre-invasive bronchial lesions before they become invasive carcinomas. We conducted a detailed investigation into the use of fluorescence bronchoscopy in the detection of pre-invasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy. We also studied the distinctive cytological findings in the sputum specimens corresponding to the pre-invasive bronchial lesions. Sputum examinations were performed by mass screening a high-risk group of participants. From 1997 to 1999, 61 participants with sputum cytology suspicious or positive for malignancy were referred to our institute, and were examined with both white-light and fluorescence bronchoscopy. For the cytological findings, the collection of sputum was performed in the early morning. Conventional white-light examinations were first performed, and areas with abnormal findings were recorded for subsequent biopsy. Fluorescence bronchoscopy examinations were then carried out. Biopsy specimens for a pathological examination were taken from all the suspicious or abnormal areas discovered by the white-light bronchoscopy, or fluorescence bronchoscopy examination, or both. The laser-induced fluorescence bronchoscopic examination showed a high sensitivity for invasive carcinoma, carcinoma in situ, as well as severe, moderate, and mild dysplasia. In the sputum cytological findings, a thickened cytoplasm and slight hyperchromasia were frequently observed in the mild dysplasias compared with the squamous cells without atypia. Hyperchromasia and an Orange G (OG)-philic cytoplasm of squamous cells were frequently observed in the moderate compared with the mild dysplasias. A thickened cytoplasm, a nuclear pleomorphism, a thickened nuclear rim, a coarse chromatin, an uneven chromatin distribution, and an OG-philic cytoplasm were frequently observed in the carcinomas in situ and severe dysplasias compared with the moderate dysplasias. We found that the use of fluorescence bronchoscopy in addition to conventional white-light examination can enhance the detection and localization of pre-invasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy. Sputum cytology is therefore a potential approach to diagnosing pre-invasive bronchial lesions.