This was a prospective randomized, controlled trial (RCT). Between January 1st 2019 to September 1st 2021, EBUS and virtual bronchoscopic navigation (VBN) examination were performed in 250 consecutive patients with PPLs who were admitted to Zhangzhou Affiliated Hospital of Fujian Medical University (Fujian, China). Finally, 198 eligible patients were randomly divided into ROSE group (100 cases) and non-ROSE group (98 cases). PPLs were defined as lesions surrounded by pulmonary parenchyma and endoscopically invisible (no evidence of endobronchial lesion, extrinsic compression, submucosal tumor, narrowing, inflammation, or bleeding of the bronchus) . Inclusion criteria: chest CT revealed PPLs which was less than or equal to 3 cm in diameter. Exclusion criteria: severe emphysema, multiple or single bullae in lung parenchyma near to pulmonary lesions, cardiac or pulmonary function insufficiency, hemorrhagic diseases or coagulation disorders, and mental disorder, pregnant women, unable to stop anti-platelet aggregation drugs, patients with advanced peripheral lung cancer and other conditions that cannot cooperate with bronchoscopy.
The study was approved by the ethical committee of Zhangzhou Affiliated Hospital of Fujian Medical University (ethics approval no. Zzsyy-2017-1116), and all patients provided informed written consent.
Biopsy procedure by EBUS and VBN
The location of the bronchus leading to the lesion was designed by VBN in advance (Ziostation2;Ziosoft Ltd, Tokyo, Japan; LungPoint; Bronchus Ltd, Mountain View, CA, USA; or DirectPath, Olympus Ltd, Tokyo, Japan). Bronchoscopy was performed applying a fiberoptic bronchoscope in combination with the R-EBUS (20MHz mechanical-radial type, UM-S20-20R or UM-S20-17S; Olympus, Japan) and guide sheath (GS) kit (K-201 or K-203; Olympus, Japan). The scope was inserted through the oral route, and each procedure was performed under local anesthesia with intravenous administration of midazolam for mild sedation. X-ray fluoroscopy (VersiFlex VISTA, Hitachi, Japan) was applied to guide the insertion of the R-EBUS probe with GS through the working channel of the bronchoscope until the target site was reached.
After determining the location of the R-EBUS probe and GS within a target lesion, brushing and TBB cytology were perfromed for specimen collection. When the R-EBUS probe was adjacent to or outside the target lesion, the bronchus closest to the PPLs was meticulously searched under fluoroscopy prior to collecting specimen. X-ray fluoroscopy guidance was applied during biopsy and brushing sampling, as well as during removal of the GS after sampling. The procedure time was measured based on the interval between insertion and removal of the bronchoscope through the vocal cords. The diagnosis time was measured based on the interval between the R-EBUS operation to final pathological diagnosis. And the expense during diagnosis indicated the costs between the R-EBUS operation to final pathological diagnosis.
Rapid on-site specimen evaluation
The material obtained from bronchoscopic biopsy or brushing, was immediately expressed onto numbered glass slides. Diff stain was applied for specimen staining (Diff-Quik; Sysmex Ltd. Kobe, Japan). The stained slide was screened by the same experienced cytopathologist, who continuously reported the findings in real time and announced when sufficient diagnostic material had been obtained for a provisional diagnosis. The bronchoscopist modified or terminated the sampling process according to the information provided by the cytopathologist. Then tissue biopsy samples were placed in 10% formalin and were embedded in paraffin for routine histologic evaluation on hematoxylin and eosin staining.
Positive diagnostic criteria for ROSE: (1) The ROSE cytology showed cancer cells and nuclear heterogeneous cells; (2) The ROSE reported neutrophils, and lesions absorpted after anti-infective treatment; (3) The ROSE showed lymphocytes and other inflammatory cells.
For those non-diagnostic patients, the final diagnosis was determined through additional medical examinations such as CT-guided percutaneous lung biopsy, surgical biopsy or anti-infection, anti-tuberculosis therapy and follow-up for at least 6 months.
Evalutaion of complication:
Complications are considered as follows: severe bleeding (bleeding volume>50ml), pneumothorax, malignant arrhythmia, lidocaine poisoning, monitoring blood oxygen saturation <90%, blood pressure greater than 180/120 mmHg or less than 90/60mmHg, consciousness disorder or other adverse events.
SPSS version 20.0 (SPSS, Inc., Armonk, NY, USA) was applied for statistical analyses. All variables were evaluated for normal distribution prior to analysis. Non-normally distributed continuous variables were expressed as the median (Md) and interquartile range (IQR), using Kruskal–Wallis H (K) for multiple-group comparison. Normally distributed data were expressed as mean±SD, using a Student’s t test or one-way ANOVA for comparison. Categorical variables were presented as number (percentage), using the chi-square test or Fisher’s exact test when compared. Differences were considered to indicate significance if a p value was <0.05.