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Original Research: Pulmonary Procedures |

Feasibility and Safety of Bronchoscopic Transparenchymal Nodule Access in CaninesBronchoscopic Transparenchymal Nodule Access: A New Real-Time Image-Guided Approach to Lung Lesions FREE TO VIEW

Gerard A. Silvestri, MD, FCCP; Felix J. Herth, MD, FCCP; Thomas Keast, BSME; Lav Rai, PhD; Jason Gibbs, PhD; Henky Wibowo, MSECE; Daniel H. Sterman, MD, FCCP
Author and Funding Information

From the Division of Pulmonary and Critical Care Medicine (Dr Silvestri), Medical University of South Carolina, Charleston, SC; Department of Pneumology and Critical Care Medicine (Dr Herth), Thoraxklinik, University of Heidelberg and Translational Lung Research Center, Heidelberg, Germany; Broncus Medical, Inc (Messrs Keast and Wibowo and Drs Rai and Gibbs), Mountain View, CA; and Hospital of the University of Pennsylvania (Dr Sterman), Philadelphia, PA.

Correspondence to: Gerard A. Silvestri, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, 96 Jonathan Lucas St, Ste 812-CSB, Charleston, SC 29425; e-mail: silvestri@musc.edu


Funding/Support: This study was funded by Broncus Medical, Inc.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(4):833-838. doi:10.1378/chest.13-1971
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Background:  The current approaches for tissue diagnosis of a solitary pulmonary nodule are transthoracic needle aspiration, guided bronchoscopy, or surgical resection. The choice of procedure is driven by patient and radiographic factors, risks, and benefits. We describe a new approach to the diagnosis of a solitary pulmonary nodule, namely bronchoscopic transparenchymal nodule access (BTPNA).

Methods:  In anesthetized dogs, fiducial markers were placed and thoracic CT images acquired. From the CT scan, the BTPNA software provided automatic point-of-entry prescribing of a bronchoscopic path (tunnel) through parenchymal tissue directly to the lesion. The preplanned procedure was uploaded to a virtual bronchoscopic navigation system. Bronchoscopic access was performed through the tunnels created. Proximity of the distal end of the tunnel sheath to the target was measured, and safety was recorded.

Results:  In four canines, 13 tunnels were created. The average length of the tunnels was 32.3 mm (range, 24.7-46.7 mm). The average proximity measure was 5.7 mm (range, 0.1-12.9 mm). The distance from the pleura to the nearest point within the target was 7.4 mm (range, 0.1-15 mm). Estimated blood loss was < 2 mL per case. There were no pneumothoraces.

Conclusions:  We describe a new approach to accessing lesions in the lung parenchyma. BTPNA allows bronchoscopic creation of a direct path with a sheath placed in proximity to the target, creating the potential to deliver biopsy tools within a lesion to acquire tissue. The technology appears safe. Further experiments are needed to assess the diagnostic yield of this procedure in animals and, if promising, to assess this technology in humans.

Figures in this Article

The diagnosis and management of solitary pulmonary nodules has become increasingly important in the United States and abroad. The reported incidence of new noncalcified nodules in the United States is approximately 150,000 per year, but this number is likely low because the studies reporting this estimate were performed in an era of chest radiograph use. The estimates do not take into account the widespread use of CT imaging, a much more sensitive tool increasingly used in diagnostic algorithms for a myriad of chest disorders.

Once a nodule is detected, there are essentially three management strategies: watchful waiting with serial surveillance, biopsy, or surgical resection.1,2 The choices are based on the pretest probability that the lesion is cancer, the patient’s ability to undergo invasive testing and treatment, and patient preferences. When biopsy is chosen, the preferred method is either transthoracic needle aspiration (TTNA) or bronchoscopy. TTNA is used to make a diagnosis in patients approximately 90% of the time but is associated with a significant rate of pneumothorax (15%), of which 6% require chest tube placement.2,3 The yield for traditional flexible bronchoscopy for the diagnosis of a solitary pulmonary nodule has been poor, with yields ranging from 13% to 60% depending on the size and location of the nodule.4,5 However, a meta-analysis reported a pooled yield of 70% with different types of guided bronchoscopy and a favorable safety profile, with pneumothorax rates < 2% of which < 1% required chest tube placement.6 Finding an approach that combines the high diagnostic yield of TTNA with the favorable safety profile of bronchoscopy is warranted.

Bronchoscopic transparenchymal nodule access (BTPNA) is a new technique that allows access to a lung lesion from the airway through a direct pathway from the bronchus without relying on the anatomy of the airway to reach the target. In theory, BTPNA combines the advantages of TTNA (direct path to the nodule with high yield from biopsy) with the advantages of bronchoscopy (low complication rate). This article describes this new technique, the measurements for reaching the target, and the safety profile.

This study was performed in canines (weight, approximately 20 kg) using best practices. The study was approved by the Institutional Animal Care and Use Committee at the University of Utah. All dogs were killed afterward. The animal studies were conducted between June and July 2011. The procedure has two distinct aspects: preprocedural planning and BTPNA.

Preprocedural Planning

The animals were sedated with propofol approximately 6 mg/kg IV for transport. Once in the supine position for bronchoscopy, inhaled isoflurane 1% to 3% was administered to maintain a stable plane of anesthesia throughout the procedure. Fiducial markers were then bronchoscopically placed in various distal locations in the lung parenchyma of the anesthetized dogs. The fiducial marker used in this study was the Align 0.8 × 10 mm gold (MTNW887883; CIVCO Medical Solutions), which was bisected along the length to produce two 5-mm long markers. These were implanted in the canines by (1) fiducial marker front-loading into the tip of a FleXNeedle (Broncus Medical, Inc), a transbronchial needle aspiration needle, and securing it with a small amount of Surgilube (Savage Laboratories, a Division of Fougera Pharmaceuticals, Inc), (2) transbronchial penetration in a deep peripheral airway of the targeted lobe, and (3) advancement of a stylet through the FleXNeedle to expel the fiducial marker from the lumen into the parenchymal location. Because the left upper lobe of dogs has minimal lung parenchyma, placing fiducial markers was not possible; thus, they were only placed in three of the four lobes.

Thoracic CT images (SOMATON Sensation 16; Siemens AG) were acquired for each animal with a 0.75-mm slice thickness and 0.5-mm overlap. From these CT scans, the BTPNA software (Broncus Medical, Inc) provided automatic point-of-entry (POE) plans (Fig 1A). The BTPNA software comprises new code that was integrated with the commercial virtual bronchoscopic navigation (VBN) version of the LungPoint software (Broncus Medical, Inc) to function as a single system. The POE plan prescribes a bronchoscopic path, location, and orientation such that a vessel-free, straight-line path (tunnel) can be created from the POE, typically located in a central airway, through parenchymal tissue directly to the lesion. The software builds a vascular tree during three-dimensional reconstruction of the CT image data and provides a variety of visualization tools to ensure that users avoid vascular injury during tunneling. The POE locations were chosen for safety and bronchoscopic accessibility (Fig 1B). The preplanned procedure was uploaded to the VBN system integrated with BTPNA software algorithms for intraoperative guidance.

Figure Jump LinkFigure 1. Bronchoscopic transparenchymal needle access software guidance views of the endoluminal and parenchymal point of entry and tunnel. A, The virtual bronchoscopic view shows the point of entry (green) and the highlighted parenchymal lesion (gray, blue). B, The CT image slice shows surrounding parenchyma along the planned tunnel (red) to confirm the absence of vessels, airways, or other obstacles.Grahic Jump Location

A fluoroscope (Model OEC 9800; GE Healthcare) provided live thoracic imaging. The video output from the fluoroscope was routed to the software system. Each animal was anesthetized in a supine position, after which the fluoroscopic image was registered to the preoperative CT scanner. The registration superimposed the CT imaging data comprising the planned trajectory and the target onto the live fluoroscopic video feed. The fusion of the CT imaging data and fluoroscopic video shows, in real time, the position of the diagnostic tools and the superimposed target, even as the C-arm is moved around the animal.

Bronchoscopy With BTPNA

Bronchoscopic access was initiated with a 2.8-mm working channel, 6.0-mm outer diameter video bronchoscope (Model BF-1T160; Olympus Corp of America) through a 10-mm endotracheal tube. Navigation was directed through VBN along the preoperatively planned route to the target’s entry location. The BTPNA software provided guidance for the specific bronchoscopic location and orientation for penetration. Figure 2 shows the four steps of the tunneling procedure. At the POE, the procedure proceeded as follows: (1) an 18-gauge needle (FleXNeedle) was used to pierce the airway wall; (2) a balloon catheter (4.0 mm outer diameter × 6.0 mm length) was inserted into the opening and inflated to 10 atm (the balloon remained inflated for 5 s to enlarge the opening); (3) a 2.0-mm working channel sheath was advanced into the enlarged opening; and (4) the sheath was locked to a 15-gauge stylet, and, together, they were advanced to the lesion under fused CT scan/fluoroscopic guidance. The CT imaging data were extracted from the software but superimposed on the live fluoroscopic video feed. The completion of this sequence resulted in a parenchymal tunnel that enabled nodule access with 2.0-mm compatible tools while the sheath remained in place.

Figure Jump LinkFigure 2. The four steps of the tunneling procedure. A, Needle penetration. B, Balloon dilation. C, Sheath insertion into dilated passage. D, Observation of tunnel after sheath removal.Grahic Jump Location

After penetration and before advancement of the sheath through the parenchyma, positioning was confirmed by overlaying CT imaging-defined targets and tunnels onto the live fluoroscopy (Fig 3). The sheath was made from radiopaque materials and was visible in the fluoroscopic video feed. The POE marker and guide rails were superimposed onto the fluoroscopic video. As the C-arm unit was repositioned, the fused fluoroscopy view was updated in real time, allowing for confirmation of the tunnel positioning in multiple imaging planes and alleviating the difficulties that can arise when interpreting two-dimensional fluoroscopic projections.

Figure Jump LinkFigure 3. Fused fluoroscopic view of a bronchoscopic transparenchymal needle access procedure in the left lower lobe of a canine subject. The view shows the preplanned tunnel (parallel lines) extending 35 mm from the point of entry on the airway wall to the parenchymal lesion (10-mm major axis, blue). The sheath advanced from the point of entry is shown within the preplanned tunnel, and its distal tip (arrow) is positioned in front of the lesion, providing straight-line access to the lesion.Grahic Jump Location
Study End Points

Proximity to target was defined as the distance (in millimeters) from the end of the sheath to the nearest edge of the fiducial marker (Fig 4). Fluoroscopic video was captured to still image files, and measurements were obtained with Photoshop software version CS4 (Adobe Systems Inc) by first calibrating to a 15.85-mm stainless steel ball in the fluoroscopic view (placed next to the animal during the procedure). Fluoroscopic measurements were acquired in five projections as follows: anterior/posterior view, 30° to cranial, 30° to caudal, 30° to the left, and 30° to the right of the fiducial markers. The greatest of the five measurements was recorded to ensure that the measurement corresponded to the true spatial distance between the end of the sheath and the nearest edge of the fiducial marker. Measurements were taken during expiration. For the VBN-guided measures, the fiducial marker was masked by placing a virtual target overlay at its location because many lung lesions in humans are not radiopaque like the fiducial markers used in this study. In addition, if the target is easily visible through fluoroscopy, then it would likely be easier to navigate to it, making it impossible to distinguish the accuracy of the VBN system from the skill of the bronchoscopist to reach a visible object in space. Thus, the virtual target overlay blinded the bronchoscopist but still allowed a measure of proximity to the visible target (fiducial marker) once the overlay was removed.

Figure Jump LinkFigure 4. Proximity to target. A, Representative fluoroscopic image. B, Magnified view with corresponding distance between the fiducial marker (green arrow) and sheath (blue arrow).Grahic Jump Location

The main findings of the study are summarized in Table 1. In total, four canines had 13 tunnels created. Bronchoscopies were performed by two operators (T. K. and H. W.). Software support was managed by two investigators (L. R. and J. G.), and fluoroscopy was performed by one investigator (J. G.). The right upper and lower lobes of each lung were accessed. The average length of the tunnels created from the POE of the airway to the fiducial marker was 32.3 mm (range, 24.7-46.7 mm). The average proximity measure was 5.7 mm (range, 0.1-12.9 mm). The distance from the pleura to the nearest point within the target was 7.4 mm (0.1-15 mm). The duration of the procedure from the initiation of the POE to the initiation of target access averaged 14.4 min (range, 8-26 min). The procedure was safe. There were no pneumothoraces reported with the tunneling either during or within 60 min postprocedure. Only minor bleeding (estimated < 2 mL) occurred during any tunneling procedure.

Table Graphic Jump Location
Table 1 —Procedural Characteristics

LLL = left lower lobe; RLL = right lower lobe; RUL = right upper lobe.

To our knowledge, this is the first description of the new BTPNA procedure, which combines bronchoscopic tools and techniques with VBN to allow the operator to produce a tunnel directly from the airway to the lesion of interest. The study goals were accomplished in three important ways. First, the computer algorithms enabled the creation of the shortest direct path from the airway to the target in every case while avoiding blood vessels. Second, a sheath through which standard bronchoscopic tools could be used was placed in proximity to the target, a necessary requirement if one hopes to increase the yield of biopsy specimens. Third, the procedure was safe, with minimal bleeding and no pneumothoraces in a small number of animals.

When biopsy tissue is necessary for the diagnosis of a pulmonary nodule, the current approaches are bronchoscopy with navigation, TTNA, or surgical resection. Each approach has its own advantages, disadvantages, risks, and benefits. Surgery remains the gold standard, with a diagnostic yield approaching 100%.2 However, it has the highest morbidity of the three procedures, and although extremely rare, surgical resection can be fatal. In some patients with comorbid conditions, the risk is too high to consider surgery. TTNA biopsy has a yield of around 90% but is associated with a significant rate of pneumothorax (15%) of which 6% require a chest tube.2,3 Central lesions and patients with underlying emphysema pose the highest risk for complications, and 1% of patients undergoing TTNA experience major hemorrhage.3

Bronchoscopy with navigation has the lowest pooled diagnostic yield of the three procedures (70%) but has the best safety profile (< 1% pneumothorax rate requiring chest tube).6 Why is the yield not higher with navigation bronchoscopy? The answer probably lies in the inherent limitations of the bronchoscope and the challenges presented by the location of the nodule and its proximity to an airway. Normal-sized adult bronchoscopes are limited by their diameter, can only reach about the fourth- to fifth-generation airway, and are unable to advance further. Even with the increasing use of bronchoscopes with a smaller outer diameter (4.2 mm), it can be difficult in certain circumstances to articulate the scope through the bronchial tree to the area of interest. Furthermore, accessing the lesion successfully with standard bronchoscopic biopsy techniques depends on the airway anatomy. If an airway forks before the lesion, then the target will lie adjacent to the airway, making biopsy difficult. How might BTPNA, then, add to our diagnostic armamentarium in the evaluation of solitary pulmonary nodules? In theory, this technology could take advantage of the best qualities of TTNA and bronchoscopy by providing a direct path to the lesion (TTNA) coupled with an excellent safety profile (bronchoscopy).

This study has several limitations. First, the number of tunnels created was small. However, in this and previous experiments not designed to assess proximity to the target, 44 tunnels were made in 10 animals without pneumothorax or bleeding (Table 2). Second, because the animals presumably had normal lungs, the rate of pneumothorax may be lower than that seen in a human study, especially if tunnels are being created in patients with emphysema. Third, the study bronchoscopies were performed by company engineers, and although they had experience performing bronchoscopy on animals, they are not expert, classically trained interventional pulmonologists. However, the physician investigators involved in this study were intimately involved in the development of the BTPNA procedure and in the planning, design, and analysis of all the animal cases, and two of the three interventional pulmonologists had performed subsequent animal and human studies with similar results. Fourth, the vascular anatomy of a dog is different from that of humans, making it difficult to assess bleeding. However, although canine pulmonary vasculature has some differences from human pulmonary vasculature, the current research indicates that it has the most similar structure to humans of the species that could be effectively and economically studied. Finally, this study was not designed to assess diagnostic yield, so direct comparisons to the other procedures regarding this cannot be made.

Table Graphic Jump Location
Table 2 —Tunnels Created for Proof of Principle and Assessment of Safety

See Table 1 legend for expansion of abbreviations.

In summary, we describe a new approach to accessing lesions in the lung parenchyma. BTPNA provides bronchoscopic creation of a direct path to a target and places a sheath in proximity to the target, which creates the potential to deliver biopsy tools through a sheath to the lesion to acquire tissue. The technology appears safe. Further experiments are needed to assess the diagnostic yield of this procedure in animals and, if promising, to assess this technology from the standpoint of both safety and efficacy in humans.

Author contributions: Dr Silvestri had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Silvestri: contributed to the design, analysis of results, and writing of the manuscript.

Dr Herth: contributed to the design, analysis of results, and writing of the manuscript.

Mr Keast: contributed to the performance of the experiment, design, data analysis, and review of the manuscript.

Dr Rai: contributed to the performance of the experiment, design, data analysis, and review of the manuscript.

Dr Gibbs: contributed to the performance of the experiment, design, data analysis, and review of the manuscript.

Mr Wibowo: contributed to the performance of the experiment, design, data analysis, and review of the manuscript.

Dr Sterman: contributed to the design, analysis of results, and writing of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Drs Silvestri, Herth, and Sterman have received consulting fees from Broncus Medical, Inc. Drs Silvestri and Herth have received grant funding for this and other studies performed for Broncus Medical, Inc. Messrs Keast and Wibowo and Drs Rai and Gibbs are employees of Broncus Medical, Inc.

Role of sponsors: Messrs Keast and Wibowo and Drs Rai and Gibbs, as employees of the sponsor, contributed to the design of the study, the collection and analysis of the data, and preparation of the manuscript.

BTPNA

bronchoscopic transparenchymal nodule access

POE

point of entry

TTNA

transthoracic needle aspiration

VBN

virtual bronchoscopic navigation

Gould MK, Fletcher J, Iannettoni MD, et al; American College of Chest Physicians. Evaluation of patients with pulmonary nodules: when is it lung cancer? ACCP evidence-based clinical practice guidelines (2nd ed). Chest. 2007;132(3_suppl):108S-130S. [CrossRef]
 
Wahidi MM, Govert JA, Goudar RK, Gould MK, McCrory DC; American College of Chest Physicians. Evidence for the treatment of patients with pulmonary nodules: when is it lung cancer? ACCP evidence-based clinical practice guidelines (2nd ed). Chest. 2007;132(3_suppl):94S-107S. [CrossRef]
 
Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med. 2011;155(3):137-144. [CrossRef]
 
Rivera MP, Mehta AC; American College of Chest Physicians. Initial diagnosis of lung cancer: ACCP evidence-based clinical practice guidelines (2nd ed). Chest. 2007;132(3_suppl):131S-148S.
 
van ’t Westeinde SC, Horeweg N, Vernhout RM, et al. The role of conventional bronchoscopy in the workup of suspicious CT scan screen-detected pulmonary nodules. Chest. 2012;142(2):377-384. [CrossRef]
 
Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. Chest. 2012;142(2):385-393. [CrossRef]
 

Figures

Figure Jump LinkFigure 1. Bronchoscopic transparenchymal needle access software guidance views of the endoluminal and parenchymal point of entry and tunnel. A, The virtual bronchoscopic view shows the point of entry (green) and the highlighted parenchymal lesion (gray, blue). B, The CT image slice shows surrounding parenchyma along the planned tunnel (red) to confirm the absence of vessels, airways, or other obstacles.Grahic Jump Location
Figure Jump LinkFigure 2. The four steps of the tunneling procedure. A, Needle penetration. B, Balloon dilation. C, Sheath insertion into dilated passage. D, Observation of tunnel after sheath removal.Grahic Jump Location
Figure Jump LinkFigure 3. Fused fluoroscopic view of a bronchoscopic transparenchymal needle access procedure in the left lower lobe of a canine subject. The view shows the preplanned tunnel (parallel lines) extending 35 mm from the point of entry on the airway wall to the parenchymal lesion (10-mm major axis, blue). The sheath advanced from the point of entry is shown within the preplanned tunnel, and its distal tip (arrow) is positioned in front of the lesion, providing straight-line access to the lesion.Grahic Jump Location
Figure Jump LinkFigure 4. Proximity to target. A, Representative fluoroscopic image. B, Magnified view with corresponding distance between the fiducial marker (green arrow) and sheath (blue arrow).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Procedural Characteristics

LLL = left lower lobe; RLL = right lower lobe; RUL = right upper lobe.

Table Graphic Jump Location
Table 2 —Tunnels Created for Proof of Principle and Assessment of Safety

See Table 1 legend for expansion of abbreviations.

References

Gould MK, Fletcher J, Iannettoni MD, et al; American College of Chest Physicians. Evaluation of patients with pulmonary nodules: when is it lung cancer? ACCP evidence-based clinical practice guidelines (2nd ed). Chest. 2007;132(3_suppl):108S-130S. [CrossRef]
 
Wahidi MM, Govert JA, Goudar RK, Gould MK, McCrory DC; American College of Chest Physicians. Evidence for the treatment of patients with pulmonary nodules: when is it lung cancer? ACCP evidence-based clinical practice guidelines (2nd ed). Chest. 2007;132(3_suppl):94S-107S. [CrossRef]
 
Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med. 2011;155(3):137-144. [CrossRef]
 
Rivera MP, Mehta AC; American College of Chest Physicians. Initial diagnosis of lung cancer: ACCP evidence-based clinical practice guidelines (2nd ed). Chest. 2007;132(3_suppl):131S-148S.
 
van ’t Westeinde SC, Horeweg N, Vernhout RM, et al. The role of conventional bronchoscopy in the workup of suspicious CT scan screen-detected pulmonary nodules. Chest. 2012;142(2):377-384. [CrossRef]
 
Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. Chest. 2012;142(2):385-393. [CrossRef]
 
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