Bronchoscopic transparenchymal nodule access in the diagnosis and management of pulmonary nodules

To the Editor: Transthoracic needle aspiration (TTNA) and bronchoscopy have been the preferred methods for the sampling of pulmonary nodules suspected of lung cancer. However, despite having a higher diagnostic accuracy, TTNA has been associated with a high rate of pneumothorax. Moreover, conventional bronchoscopy with a low rate of pneumothorax has exhibited a low diagnostic yield for peripheral pulmonary nodules, particularly for nodules <2 cm in size or those without a bronchus leading directly to them. Thus, Herth et al^[1] developed a novel bronchoscopy technique called bronchoscopic transparenchymal nodule access (BTPNA) under the guidance of Archimedes Virtual Bronchoscopic Navigation (VBN) System for the purpose of accessing pulmonary nodules using a transparenchymal approach without relying on the airway to approach the lesion. Here, we systematically reviewed evidence regarding BTPNA to provide general guidance on the safe implementation and development of this novel approach.

Computed tomography (CT) data were uploaded onto the Archimedes System to construct a three-dimensional (3D) model of the bronchial airways, ribs and lungs, and vascular structures to mark and segment the lesion. Two point of entry (POE) locations with a straight, vessel-free path to the lesion, and a bronchoscopy path to the POE locations are created by the system. The system also shows the tunnel path from the POE on the airway wall to the target lesions. During surgery, the Archimedes System combines real-time fluoroscopic data with 3D CT data to guide the sheath from the POE on the airway wall through the lung parenchyma directly into the pulmonary nodule. On reaching the POE position, the core needle passes through the standard therapeutic bronchoscope working channel and penetrates the airway walls at the POE in the airway. Once the proximal end is reached, the stylet is removed, biopsy forceps are inserted through the sheath, and biopsy samples are taken under fused fluoroscopy guidance [Figure 1].^[1]

Figure 1: (A) Hardware requirements of the operation room. (B) Archimedes System calculates two suitable point of entry (POE) locations with straight line, vessel-free access to the SPN, as well as bronchoscopy paths for guiding the user's bronchoscope to the POE locations. (C) Sheath tip was advanced up to the lesion through the POE. (D–E) Guide sheath being advanced to the target under fluoroscopic guidance. SPN: Solitary pulmonary nodules.

During pulmonary nodule biopsy, the diagnostic yield ranged from 38.5% to 80.0% based on a single or combination of different guided bronchoscopies, depending on the lesion size, location, and the presence of a bronchus sign (BS) on CT.^[2] In a randomized trial, the 3-mm ultrathin bronchoscope provided higher diagnostic yields for pulmonary lesions than the 4-mm thin bronchoscope combined with radial endobronchial ultrasound, VBN, and fluoroscopy (70.1% vs. 58.7%).^[3] Recently, a retrospective study showed that robot-assisted bronchoscopy appeared to be a promising approach, with a successful navigation yield of 88.6%, diagnostic yield of 69.1% to 77.0%, and pneumothorax rate of 3.6%.^[4] However, these approaches were restricted to nodules in which a BS was present. Transbronchial needle aspiration (TBNA) and transbronchial biopsy (TBB) had a diagnostic yield of only 59.1% and 22.6%, respectively, with the diagnostic yield decreasing to 31% even when electromagnetic navigation bronchoscopy was used in lesions with no BS on CT. ^[5]

In a prospective study, Sun et al^[6] evaluated the safety and efficacy of BTPNA and TBNA using the Archimedes system to diagnose peripheral pulmonary lesions. These approaches guided by the Archimedes system had a higher diagnostic yield (72.8%–75.4%) than TBB in the lesions independent of the presence of BS and even a higher diagnostic yield (71.4%–74.1%) in lesions without a BS that cannot be directly reached by bronchoscopy. Moreover, BTPNA had a relatively higher biopsy yield than guided TBNA (86.3% vs. 67.2%). Above all, BTPNA appeared to have a relatively higher diagnostic yield than other approaches used for pulmonary nodule biopsy.

Factors associated with the diagnostic accuracy of BTPNA: The BTPNA approach improves the access to peripheral pulmonary nodules via the bronchoscopy route. In a previous study, a tunnel pathway was successfully created in 83.33% (10/12) of patients. Adequate biopsies obtained from ten patients (83.33%) correlated with their histological findings following surgical resection.^[1] A global multi-center study in a real-world setting reported that biopsy yields of BTPNA were 86.3%, especially in lesions with a tunnel length ≥30 mm wherein the biopsy yield exceeded 90%.^[6]

Risk of the tunnel length created: In the first human trial evaluating BTPNA for sampling solitary pulmonary nodules, a tunnel length of 50 mm or longer was created in seven of ten patients with tunnels created, with a 90-mm long tunnel safely created and a biopsy successfully performed in one patient.^[1] We believe that there was no increased risk of adverse events regardless of the tunnel length created. However, further studies are required regarding the maximum length that can be created and the risk of adverse events.

Biopsy yield and sampling yield of the tunnel length created: A prospective study conducted by Sun et al^[6] found no significant difference in the biopsy yield between a tunnel length of <30 and ≥30 mm (78.9% vs. 90.6%, P = 0.40). Likewise, no significant difference in the sampling yield was noted between a tunnel length of <30 mm and ≥30 mm (84.2% vs. 93.8%, P = 0.34). We believe that there was no reduction in biopsy and sampling yields regardless of the tunnel length created using the BTPNA technique.

Advantages of this novel approach: Although BTPNA consists of eight procedures and appears to be more complicated than TTNA, this novel approach appears to have a high diagnostic yield accompanied by a low risk of immediate adverse events and a comparable procedure time compared with either TTNA or standard bronchoscopy biopsy. Moreover, BTPNA significantly improved the diagnostic yield of pulmonary nodules in certain anatomical locations of the lung and may play a complementary role for TTNA. We believe that BTPNA was a more appropriate choice for nodules located centrally or behind the scapula or for those whose access was blocked by two pleural planes. Furthermore, given the lower risk of pneumothorax, BTPNA appears to be a safer approach in patients with emphysema.

Therapeutic value in patients with early lung cancer: Several patients with early-stage lung cancer do not undergo surgical care due to certain contraindications. BTPNA-guided radiofrequency ablation (RFA) may facilitate the local treatment of patients with early-stage lung cancer in this subgroup of patients.

In a study evaluating the feasibility and safety of BTPNA-guided RFA, ablation was performed by deploying an RFA catheter in conjunction with automatic saline micro-perfusion with a guide sheath into the center of the nodule through a tunnel from the POE directly into the lesion. The results showed that BTPNA-guided RFA was successful in all canines studied using simulative pulmonary nodules 10 mm in diameter and at least 10 mm away from the lower lobe pleura, without the bronchus directly leading to them. Inflammation, congestion, and coagulation necrosis of the lungs could be repaired within 7 days followed by granulation and fibrotic scar tissue development after 30 days. No accidental or procedure-related complications occurred during the operation or follow-up.^[7]

Long-term postprocedural complications: A previous study showed that patients underwent chest X-rays 2 h after the procedure followed by clinical observation for at least 72 h to evaluate the long-term postprocedural complications associated with BTPNA. The findings showed that two out of six patients had pneumothorax. One case with a maximal distance of 6 mm from the pleural surface did not need any further intervention, whereas the other case required a chest tube to resolve the pneumothorax.^[8] Moreover, no other complications were recorded within 72 h of clinical observation following BTPNA. The distance from the nodule to the pleural surface was small in both the cases (1 and 9 mm, respectively). However, the safety of the biopsy sampling in pulmonary nodules that had small distances from the nodule to the pleural surface needs to be further evaluated, and patients with this feature should not be excluded from clinical trials or clinical applications of BTPNA. We believe that patients in whom the distance from the nodule to the pleural surface is small require clinical observation following BTPNA.

Limitations of this novel approach: Entry of the apex of the lung, particularly in the left upper lobe, is blocked by the aorta and pulmonary arteries. Therefore, it is more difficult to adjust the angulation and orientation of the sheath and dissection tip to the desired direction. We believe that lesions located in the apex of the lung, particularly in the left upper lobe, should be sampled for biopsy using other diagnostic methods, such as TTNA, if possible.

This study on the application of BTPNA guided by Archimedes system is intended to offer general guidance in the biopsy of the pulmonary nodules. One of the strengths of this study is that it provides the opinions and recommendations of experts in this field. With new options, new uses of BTPNA are emerging and it's plausible that BTPNA has enormous potential to provide safe and effective diagnostic and therapeutic procedures at reduced costs for many patients with a variety of lung disorders.

Conflicts of interest

None.