The increased frequency of high-quality computed tomography (CT) application to the thorax has enabled us to identify much smaller pulmonary lesions than before.1 The diagnostic rate of malignant lesions by traditional transbronchial biopsy (TBB) ranged from 14% to 63%, depending on the size and location of the lesions2,3 and also the skill and experience of the bronchoscopist. Direct visualization of target lesions by the radial probe endobronchial ultrasonography (EBUS) and several navigation systems including electromagnetic navigation bronchoscopy and virtual bronchoscopy have been developed to improve diagnostic yields.4
Virtual fluoroscopic preprocedural planning (VFPP), which was first initiated by one of our coauthors, is a figure in which the trace lines are drawn along ductal structures such as vessels or biliary ducts related to target lesions on Ray Summation image, which is similar to fluoroscopy and made by reprojecting high resolution isotropic volumetric images. The lines can be displayed at any angle with 3D imaging, and allow us to search more easily for connecting vessels during angiography (http://www.innervision.co.jp/suite_ws/ziosoft/4dimaging/201209.html), or connecting biliary ducts during the placement of a stent. VFPP is easy to prepare from volume data from multiple detector computed tomography and workstation, and can make vessel structure-related procedures more accurate. This system was applied to bronchoscopy. The trace lines between the trachea and the target lesions are constructed along the connecting bronchus and referred to as forceps guidance under the fluoroscopy, as a new type of navigation system which has never been tried before. We therefore report its feasibility.
PATIENTS AND METHODS
Patients with peripheral lung lesions with long axis ≤30 mm were recruited consecutively at the National Hospital Organization Disaster Medical Center between January and June 2013. Lesions of pure ground glass opacity were excluded, because they could be hardly recognized on fluoroscopy or on the radial probe EBUS.
The CT examination was performed using a helical CT scanner (Aquilion64; Toshiba, Tokyo, Japan) with the following parameters: 120 kV, auto mA, 0.5 mm collimation, pitch factor 0.828, helical pitch 53, and rotation time 0.5 seconds. Helical volume data sets were acquired during single breath-hold inhalation. Images were reconstructed at 0.3 mm intervals using the chest algorithm from helical CT data and transferred to Ziostation2 (Ziosoft Inc., Tokyo, Japan), a commercially available computer workstation for performing a 3D display and quantitative analysis by image processing the volume data obtained from modalities such as CT or magnetic resonance imaging. Before conducting preprocedural planning, we reconstructed a Ray Summation image. Then, referring to the axial and coronal CT images, we drew a trace line between the trachea and the target lesion along the connecting bronchus in advance (Figs. 1A–C). In addition, we drew trace lines along neighboring bronchi that might mislead the forceps locating (Fig. 1D). The lines could be displayed at any angle with 3D virtual fluoroscopic image (Figs. 2B–D). All the virtual imaging processes were performed by 2 of the authors including a radiologist and a pulmonologist.
Each patient was premedicated using 3 to 5 mg of midazolam, if necessary. Local anesthesia of the upper respiratory tract was done by 2% lidocaine. The standard type of videobronchoscope (BF-1T260 and BF6C260; Olympus) was used. Before the procedure, we selected pictures that showed the widest angle between the connecting trace line and neighboring lines at each bifurcation on virtual images. First, we investigated all the bronchial lumens, then, a leading forceps (CC-6DR-1; Olympus) with guide sheath (GS) (SG-200C; Olympus) was inserted through the working channel of the scope and into the bronchus, which seemed by CT assessment to connect with the lesion, and advanced under fluoroscopy with simultaneous display of VFPP, so that the forceps position was as similar as possible to the line drawn on VFPP mapping. Once the leading forceps had reached the target position, we replaced the leading forceps with a 20 MHz mechanical radial probe (UM-S20-17S; Olympus) through the GS. After the lesion was confirmed by the radial probe EBUS, the probe was withdrawn and the biopsy forceps (FB-233D; Olympus) was introduced through the sheath to obtain at least 3 to 5 biopsy specimens. If the target lesion could not be visualized by the radial probe EBUS, several specimens were obtained under fluoroscopic guidance.
This study was approved by the Ethics Committee of the National Hospital Organization Disaster Medical Center, Japan. Written informed consent was obtained from each patient. The clinical research registration is UMIN000014571.
For 27 patients with 27 lesions, bronchoscopy with simultaneous display of VFPP was performed safely without major complications such as pneumothorax, massive bleeding, or pneumonia. These included 15 male and 12 female patients with a median age of 72 years (range, 26 to 87 y). The median lesion size was 20.2 mm (range, 10 to 30 mm). The lesion size was ≤20 mm in 12 lesions, >20 mm in 15 lesions. Nine lesions were located in the right upper lobe, 3 in the right middle lobe, 5 in the right lower lobe, 4 in the left upper lobe, and 5 in the left lower lobe. Five lesions could not be visualized by radiographic fluoroscopy. The median examination time was 24.5 minutes (range, 12 to 50 min). Diagnosis was made for 17 of 27 lesions (63%). In 18 lesions simultaneously visualized by the radial probe EBUS, diagnosis was made for 14 lesions (78%). Lung cancer was diagnosed in 12 lesions (adenocarcinoma, n=8; squamous cell carcinoma, n=2; metastatic colonic adenocarcinoma, n=2). Nontuberculous mycobacterial disease was diagnosed in 1 lesion, lymphoid hyperplasia in 1 lesion, and nonspecific inflammation in 3 lesions. The diagnosis of nonspecific inflammation was made when the size of the lesions decreased or disappeared during the subsequent observation period.
In 10 lesions, a diagnosis was not made. Two lesions contained a few atypical cells, but a diagnosis could not be made. Including these 2 lesions, 4 lesions were diagnosed as adenocarcinoma by open lung or transthoracic biopsy. Two lesions were highly suspected of lung cancer due to their enlarging nature in size during the observation period, and stereotactic radiosurgery was performed without definitive diagnosis after obtaining the informed consent of the patients. The other lesions are still under observation without diagnosis.
The diagnostic rate of VFPP-guided bronchoscopy was 63.0% for the 27 lesions. The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for malignant disease were 66.7%, 100%, 45.5%, 100%, and 73.9%, respectively.
Figure 2 shows the case of 69-year-old man with a pulmonary nodule measuring 17 mm in diameter in the right S2a (Fig. 2A). We performed EBUS-GS with the guidance by VFPP (Figs. 2B–D). Adenocarcinoma was diagnosed (case 1).
Figure 3 shows the case of a 62-year-old man with a pulmonary nodule measuring 29 mm in diameter in the left S1+2a (Fig. 3A). We performed EBUS-GS (Figs. 3C, D) with the guidance by VFPP (Fig. 3B). Squamous cell carcinoma was diagnosed (case 2).
The pooled diagnostic yield of guided bronchoscopy using 1 or a combination of the modalities was 70%, which was higher than that of TBB without guidance, according to the meta-analysis.4 In our study, the diagnostic yield of the pulmonary peripheral lesions (PPLs) <30 mm was approximately 60%. Recently, several guided bronchoscopic technologies have been developed to improve the yield of TBB for PPLs diagnosis: electromagnetic navigation bronchoscopy, virtual bronchoscopy with (ultra)thin bronchoscope, and EBUS-GS. Electromagnetic navigation (EMN) informs the operator where the probe is in real time by using a positional sensor. A randomized-control trial that compared the diagnostic yield of EMN-assisted bronchoscopy combined with the radial probe EBUS with that of either modality alone showed higher diagnostic yield for the combination procedure (diagnostic yield, 88% vs. 69% and 59%, respectively).5 Ishida et al6 reported a randomized trial which showed the diagnostic yield was higher for the virtual bronchoscopic navigation (VBN)-assisted EBUS-GS group than the non–VBN-assisted EBUS-GS group (80.4% vs. 67.0%). Kikuchi et al7 diagnosed 14 of 24 (58%) PPLs of <30 mm in diameter (average diameter=18.4 mm) with the radial probe EBUS-guided TBB with GS and x-ray fluoroscopy. Yamada et al8 also reported a diagnostic yield of 67% of the lesions <30 mm (the mean±SD diameter was 20.8±6.1 mm) in diameter from the radial probe EBUS-guided TBB with GS.
By using our navigation systems, the procedure time may be expected to be shorter because of the quicker positioning of the forceps within the target lesions. Prior studies demonstrated that the use of navigation tools might in some settings contribute to a shorten procedure time. The duration of the examination and the time elapsed until the start of sample collection were shorter in the VBN group than in the non-VBN group.6 Oshige et al9 also reported that the required time to determine the biopsy position was significantly less in the VBN-assisted group, though diagnostic yield for the VBN-assisted EBUS-GS group was not significantly higher than that for non–VBN-assisted EBUS-GS group.
Although these navigation systems are quite useful, they are not always available in all medical institutions. EMN is not commercially available in Japan and the locatable guides attached to the EMN sensor probe are a high cost burden. VBN, which requires an ultrathin bronchoscope also may be available in a few facilities. Moreover, even the radial probe EBUS has not been introduced in all facilities. In contrast, VFPP is easy to prepare if only we have volume data from multiple detector computed tomography and workstation. No additional cost is necessary to make VFPP, because it is made from volume data for a CT image taken for initial examination.
This pilot study has the following limitations. When making VFPP, the accuracy of planning images depends on the planner. This may influence the diagnostic yield. There were some lung cancer cases in which only atypical cells were detected without reaching a definitive diagnosis. In such cases, we should have repeated biopsy more, since the quantity of specimen is also important. Yamada et al8 reported that the number of the biopsy specimens was one of the determining factors of diagnostic accuracy. The maximum diagnostic yield was reached with at least 5 specimens from the same site.
Although the results of the study need to be interpreted with caution as the use of radial probe EBUS and the GS method might have contributed to the diagnostic yield beside the VFPP. VFPP was easy to prepare and useful for selecting the target bronchus. This study confirms feasibility of the VFPP as an adjunct to minimally invasive transbronchial biopsy of PPLs. Future randomized-controlled studies are needed to evaluate the VFPP effect on diagnostic yield and procedure duration.
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