Study patients
We retrospectively reviewed the medical records of 314 consecutive patients with EBUS-GS-guided TBB who underwent echocardiography between 6 months prior to and 1 month following bronchoscopy at the Hokkaido University Hospital, Japan, between January 2018 and June 2020. At our institution, all patients undergo a chest CT just before the EBUS-GS-guided TBB. We collected the following clinical information from all patients: age, sex, body mass index (BMI), smoking status, administration of antiplatelet agents or anticoagulant agents, CT scan features of target lesions (size and location), the requirement for additional biopsy using a larger size forceps or a flexible cryoprobe after GS removal, bronchoscopic diagnosis, which is the pathological diagnosis of specimens collected using a bronchoscope, and final diagnosis. Non-malignant outcomes, including the presence of atypical cells, fibrosis, and non-specific inflammation, were considered indeterminate results. These patients underwent further investigations, including surgical resection, to obtain a final diagnosis. The final diagnosis was considered as “undiagnosed” in the cases where EBUS-GS-guided TBB did not lead to a specific diagnosis and a follow-up chest CT was required. The medical ethics committee of the Hokkaido University School of Medicine approved the present study (Approval No. 021-0023).
Bronchoscopic procedures
After providing local pharyngeal anesthesia using 2% lidocaine, all patients were sedated via IV administration of midazolam. In most patients, we administered IV fentanyl in combination with midazolam based on a previous report [14]. All bronchoscopies were performed with intrabronchial administration of 1% lidocaine. We used one of the following combinations of bronchoscopes and guide sheath kits (Olympus, Tokyo, Japan): BF-P260F or BF-P290 (working channel diameter 2.0 mm) with a K201 guide sheath kit, or BF-1T260 or BF-1TQ290 (working channel diameter 2.8 and 3.0 mm, respectively) with a K203 guide sheath kit. EBUS-GS-guided TBB was performed according to the standard method [3]. Before the procedure, we identified the target bronchus of the lesion and evaluated the bronchus sign on a thin-slice section of the chest CT [15]. Furthermore, in most cases, we used a virtual bronchoscopic navigation system, DirectPath® (Cybernet Systems, Tokyo, Japan). We used a reusable guiding device (CC-6DR-1; Olympus) in some cases to introduce a GS into the lesion via the target bronchus. After confirming the location of the lesion using EBUS and X-ray fluoroscopy, we procured at least six biopsy samples and performed bronchial brushing thrice. Per standard current practice, we attempted to acquire over 10 biopsy specimens for molecular and histochemical analyses. To obtain larger specimens, we conducted additional biopsy using a Radial Jaw 4 Standard Pulmonary Biopsy Forceps® 1.8 mm in some cases (Boston Scientific, Natick, MA, USA), which cannot be inserted into the GS due to its large cup size, or a Cryotherapy instrument, ERBE-CRYO2® (ERBE, Tubingen, Germany), with a flexible cryoprobe (1.9-mm diameter and 1,150-mm length) after GS removal. All biopsies were performed under X-ray fluoroscopy. After undergoing EBUS-GS-guided TBB, the patients routinely underwent chest X-ray the day after the bronchoscopy.
Definition of bleeding complication
There is no consensus regarding the exact definition of bleeding associated with bronchoscopic biopsy, and it is often difficult to precisely calculate the blood loss during the procedure. In this study, bleeding was classified on a scale adapted from a previous report: [16] grade 1, suctioning of blood required for less than one minute; grade 2, suctioning required for more than one minute or repeat wedging of the bronchoscope for persistent bleeding or instillation of cold saline, diluted vasoactive substances, or thrombin; grade 3, selective intubation with endotracheal tube or balloon/bronchial blocker for less than 20 min or premature interruption of the procedure; grade 4, persistent selective intubation more than 20 min or new admission to the ICU or a need for packed red blood cell (RBC) transfusion, bronchial artery embolization, or resuscitation. In this study, we defined grade 2 or higher as a bleeding complication.
Definition of findings of suspected PH on echocardiography and chest CT
To identify patients with suspected PH, we assessed the results of echocardiography and chest CT. On echocardiography, we defined peak tricuspid regurgitation velocity (TRV) of > 2.8 m/s as a finding of suspected PH in accordance with previous reports [17, 18]. On chest CT, we measured the diameter of the main pulmonary artery at the level of its bifurcation and measured the maximum diameter of the ascending aorta using the same images, in accordance with previous literature (Fig. 2) [19]. We defined a ratio of the pulmonary artery to aorta ratio (PA:A ratio) of > 0.9 as a finding of suspected PH in accordance with previous reports [20, 21].
Statistical analysis
The data are presented as median (range) or counts and percentages. Fisher’s exact test was performed to determine the association between the variables of interest and bleeding events. We used logistic regression models for multivariate analysis. Multivariate analysis was performed using factors that were significant in the univariate analysis. Two-sided P values < 0.05 were considered statically significant. All analyses were performed using the JMP software (JMP pro, version 15.2.0; SAS Institute Inc, Cary, NC, USA).