Single-stage augmented fluoroscopic bronchoscopy localization and thoracoscopic resection of small pulmonary nodules in a hybrid operating room

Abstract

Open in new tabDownload slide

OBJECTIVES

Hybrid operating rooms (HOR) have been increasingly used for image-guided lung surgery, and most surgical teams have used percutaneous localization for small pulmonary nodules. We evaluated the feasibility and safety of augmented fluoroscopic bronchoscopy localization under endotracheal tube intubation general anaesthesia followed by thoracoscopic surgery as a single-stage procedure in ab HOR.

METHODS

We retrospectively reviewed clinical records of patients who underwent single-stage augmented fluoroscopic bronchoscopy localization under general anaesthesia followed by thoracoscopic surgery in an HOR between August 2020 and March 2022.

RESULTS

Single-stage localization and resection were performed for 85 nodules in 74 patients. The median nodule size was 8 mm [interquartile range (IQR), 6–9 mm], and the median distance from the pleural space was 10.9 mm (IQR, 8–20 mm). All nodules were identifiable on cone-beam computed tomography images and marked transbronchially with indigo carmine dye (median markers per lesion: 3); microcoils were placed for deep margins in 16 patients. The median localization time was 30 min (IQR 23–42 min), and the median fluoroscopy duration was 3.3 min (IQR 2.2–5.3 min). The median radiation exposure (expressed as the dose area product) was 4303.6 μGym² (IQR 2879.5–6268.7 μGym²). All nodules were successfully marked and resected, and the median global operating room time was 178.5 min (IQR 153.5–204 min). There were no localization-related complications, and the median length of postoperative stay was 1 day (IQR, 1–2 days).

CONCLUSIONS

Single-stage augmented fluoroscopic bronchoscopy localization under general anaesthesia followed by thoracoscopic surgery was feasible and safe.

INTRODUCTION

Lung cancer is the leading cause of cancer-related death worldwide [1]. Owing to the widespread implementation of low-dose computed tomography (CT) for lung cancer screening, large numbers of small pulmonary lesions with a high suspicion of malignancy require evaluation and management [2]. Thoracoscopic sublobar lung resection, including segmentectomy and wedge resection, has become the standard surgical procedure for both diagnostic and curative intent in suspicious nodules [3–6].

For small impalpable nodules, especially ground-glass nodules, preoperative localization is essential to achieve adequate resection, with sufficient safety margins and minimal lung volume loss [7]. Transbronchial marking using regular bronchoscopy and fluoroscopy followed by post-marking CT confirmation has been developed as an effective localization method [8–10], which can be performed without percutaneous needle localization-related complications such as pneumothorax, haemothorax and lethal air embolism [11–13]. However, most preoperative transbronchial localizations are performed under local analgesia or light sedation, which may result in patient discomfort and unavoidable cough [14, 15], which could be a primary reason why many specialists still hesitate to adopt transbronchial localization.

The hybrid operating room (HOR), which is equipped with a C-arm cone-beam computed tomography (CBCT) system, has been largely utilized for image-guided thoracic surgery [16–20]. It can provide real-time fluoroscopy during bronchoscopic procedures and CBCT scans for post-marking confirmation, which are both key elements for successful transbronchial localization [21, 22]. In addition, in the HOR, patients can receive endotracheal tube intubation general anaesthesia (ETGA) before undergoing bronchoscopy and consequent thoracoscopic surgery; importantly, there would be no patient discomfort or cough under general anaesthesia, which could facilitate transbronchial procedures and improve the results of localization.

Our team has been developing the technique of CBCT-derived augmented fluoroscopy bronchoscopy (AFB) localization for small lung nodules since 2018 [23–26], during which time all AFB localizations were performed under light sedation in the angiography room as separate preoperative procedures on the day or day before surgery. After the establishment of a new HOR with robotic C-arm CBCT (Artis pheno) in 2020, AFB localization was moved to the HOR under ETGA, followed by thoracoscopic surgery in the same suite. Here, we present our initial experience with a novel single-stage single-anaesthetic image-guided procedure for the management of small pulmonary lesions.

PATIENTS AND METHODS

Ethical statement

This study was approved by the Research Ethics Committee of the National Taiwan University Hospital, Hsin-Chu Branch (approval number: 111-091-E). Individual consent for this retrospective analysis was waived.

Study design and patients

We retrospectively reviewed consecutive patients who underwent single-stage AFB localization followed by video-assisted thoracoscopic surgery (VATS) in the HOR at the National Taiwan University Hospital, Hsin-Chu Branch, between August 2020 and March 2022. The surgical indications were: (i) persistence of a nodule with a solid component of 5 mm or more on follow-up CT and (ii) persistence of non-solid nodules larger than 10 mm with interval growth or development of a solid component. In patients with stationary sub-centimetre nodules with a solid component of <5 mm, tumour excision was performed at the patient’s request. Solid nodules with a clear, morphologically benign appearance were not recommended for intervention. The following preoperative CT findings of pulmonary nodules were considered indications for localization before thoracoscopic surgery: (i) maximum diameter <10 mm, (ii) minimum distance between the visceral pleura and nodule centre >20 mm or (iii) the presence of ground-glass opacity.

Workflow

Video 1 shows the steps of the entire workflow.

Anaesthesia and preparation for augmented fluoroscopy

The entire single-stage AFB-VATS procedure was performed in an HOR equipped with a robotic C-arm CBCT system (ARTIS Pheno; Siemens Healthcare GmbH, Erlangen, Germany) and Magnus surgical table (Maquet Medical Systems, Wayne, NJ, USA). After induction of general anaesthesia and insertion of a single-lumen tube, the patient was placed in a lateral position with the operation site up. Under end-inspiratory breath-hold phase, which was maintained by clamping the endotracheal tube with a haemostat, we obtained an initial scan with a 4-second acquisition protocol (4 s Dyna-CT Body) to cover the hemithorax of the lesion side. CBCT imaging data were transferred to a nearby workstation (syngo X-Workplace; Siemens Healthcare GmbH, Forchheim, Germany), and the target pulmonary lesion was identified and marked using semi-auto segmentation software (syngo iGuide Toolbox; Siemens Healthcare GmbH) (Fig. 1A). The marked contours were then shown on a two-dimensional fluoroscopy live screen in accordance with their corresponding three-dimensional (3D) locations; thus, the augmented fluoroscopy system was configured.

Bronchoscopic localization with dye and microcoil

The bronchoscopic procedure was performed under the guidance of CBCT-augmented fluoroscopy, and an ultrathin bronchoscope (BF-MP290F; Olympus, Tokyo, Japan) was inserted through the endotracheal tube to the distal bronchus (Fig. 1B). Indigo carmine (20 mg/ml) (Indigo Carmine; Sigma-Aldrich, St. Louis, USA) was mixed with iopromide (Ultravist 370; Bayer, Berlin, Germany) for dye marking, which provided better visualization of the dye under fluoroscopy. After identifying the nearest bronchi that could lead to the target lesion, a 4-Fr straight-tip catheter (Impress^®; Merit Medical Systems, Utah, USA) was inserted into the orifice, and the discrepancy between the marked lesion and the catheter tip was assessed in a timely manner in the augmented fluoroscopic system. The C-arm fluoroscope can be rotated to different angles to confirm that the catheter tip has reached the target. If the lesion can be directly reached by the catheter, a single pleural dye marking should be adequate for localization. Generally, the lesion cannot be reached, and the marking plan is changed to multiple markings (lung mapping) surrounding the target lesion. Each pleural dye marking was made by injection with 0.25 ml of contrast-mixed dye solution followed by the injection of 5–10 ml air. For deep-seated lesions, microcoils (Tornado^® 0.035 inch 7–3 mm 8 cm; Embolization Microcoil™; Cook Medical, Bloomington, IN, USA) can be placed transbronchially as the inner reference for either the target lesion or the safety margin. Before installing the microcoil, an additional CBCT scan was optionally performed to confirm the position of the catheter, before the microcoil was passed through the catheter using a guidewire (Radifocus™ Guide Wire 0.032 inch 150 cm; Terumo Medical, Somerset, NJ, USA) and gradually deployed to the target under augmented fluoroscopic guidance (Fig. 1C).

Image confirmation and reconstruction

After the AFB localization procedure, a confirmation scan was performed to check the location of the dye markers and their geometric relationship to the target lesion. In the confirmation CBCT images, the areas of contrast-mixed dye can be distinctly recognized and contoured using segmentation software (Fig. 2A); the markers near the pleura were considered valid and visible under thoracoscopy, otherwise, those located >2 cm from the pleura were regarded as ‘central injection’ that could be invisible. The image auto-georeferencing of the initial and last scans can be performed using the syngo workstation, and the segmentation contour of the target lesion in the initial scan can be fused in the image of the confirmation scan (Fig. 2B). Fusion can help identify the location of the target lesion that could be masked by the contrast-mixed dye in the image of the confirmation scan, particularly for ground-glass lesions. After completing all segmentations of the dyes and target lesion, the images of 3D reconstruction were processed by removing bony parts with only the lung field remaining, and the resection plan was prepared on the final 3D images (Fig. 2C).

Thoracoscopic surgery

Thoracoscopic surgery was performed at the end of the last CBCT scan. A bronchial block was inserted into the endotracheal tube for one-lung ventilation, and the patient was placed in the standard lateral decubitus position with upper arm support and lateral flexion. The surgical site was sterilized and draped for thoracoscopic surgery. Thoracoscopic resection was performed with the guidance of the multiple superficial dye markings (Fig. 2D) and centrally placed microcoils, which served as fiducial markers detected by intraoperative C-arm fluoroscopy (Fig. 1D). Either lymphadenectomy with nodal dissection or sampling was performed for the suspected primary lung cancers.

Data collection

Clinical data, operative findings and pathological characteristics of the lung nodules were collected from medical records. The lesions were measured using preoperative CT images. Lesion size was defined as the largest diameter observed on the axial view, and lesion depth was defined as the smallest distance from the centre of the lesion to the pleura. The length of the safety margin was defined as the distance between the lesion and the closest staple line in the first resection specimen. The ratio of margin/lesion was defined as the length of safety margin divided by the lesion size. The total accumulated dose of radiation exposure, expressed as the dose area product, was retrospectively calculated using data stored in the ARTIS workstation (Syngo Workplace). Preparation time for the initial scan was defined as the time between completion of anaesthesia induction and start of the first CBCT scan. Localization time was defined as the time between the first and last CBCT scans. Preparation time for surgery was defined as the time between the last CBCT scan and the skin incision.

Statistical analysis

Descriptive statistics for continuous data were summarized as medians with interquartile ranges (IQR) and means with standard deviations; for categorical data, they were summarized as counts (percentages).

RESULTS

Patient and lesion characteristics

During the study period, 85 lesions in 74 patients underwent single-stage AFB localization followed by thoracoscopic resection in the HOR. Patient and lesion characteristics are presented in Table 1. Sixty-four patients had a single pulmonary nodule and 10 patients had multiple nodules. According to the preoperative CT findings, 60 (70.6%) pulmonary nodules were classified as ground-glass nodules and 25 (29.4%) were classified as solid nodules. The nodules had a median size of 8.0 mm (IQR 6.0–9.0 mm) and a median distance from the pleural surface of 10.9 mm (IQR 8.0–20.0 mm).

Localization and surgical procedures

Table 2 summarizes the details of the localization and surgical procedures. The median anaesthesia induction time was 15 min (IQR 10–20 min) and the median preparation time for the first CBCT scan was 18 min (IQR 13–22 min). During the AFB procedure, the median duration of the bronchoscopy and fluoroscopy were 19 min (IQR 15–28 min) and 3.3 min (IQR 2.2–5.3 min), respectively. Sixteen patients underwent localization with dye marking and microcoil placement, and 58 patients received dye marking only. The median localization time was 30 min (IQR 23–42 min), and no localization procedure-related complications, such as pneumothorax, were noted. Forty-nine patients received 2 DynaCT scans, and 25 patients received >2 scans. The median total dose area product, including both DynaCT scan(s) and fluoroscopy, was 4303.6 μGym² (IQR 2879.5–6268.7 μGym²). All 85 lesions, along with the marked area, were successfully resected using thoracoscopy. A total of 82 wedge resections and 3 segmentectomies were completed, and the median operating time was 69.5 min (IQR 52–92 min). The median length of safety margin was 14 mm (IQR 10–18 mm), and the median ratio of margin/lesion was 2.0 (IQR 1.2–2.8). Five wedge resections were followed by additional resections along the staple line for acquiring more safety margin. The median number of resected lymph nodes was 9 (IQR 7–15) with nodal dissection (n = 9) and 2 (IQR 1–4) with nodal sampling (n = 44). The median duration under anaesthesia was 156.5 min (IQR 134–181 min), and the median global operating room time was 178.5 min (IQR 153.5–204 min).

Final pathological diagnoses

Table 3 shows the final pathological diagnoses and staging of primary lung cancers. There were adenocarcinoma in site (n = 17), minimally invasive adenocarcinoma (n = 15), invasive adenocarcinoma (n = 29), lung metastases (n = 2) and benign lung lesions (n = 22). All patients were successfully discharged from hospital, and the median length of postoperative stay was 1 day (IQR 1–2 days).

DISCUSSION

The current case series demonstrates the feasibility of single-stage AFB-VATS under general anaesthesia in the HOR. Our previous AFB localization procedures [23–26] were performed under light sedation with spontaneous breathing, and the patient was fixed using a vacuum bag, which could only restrict the motion of the body; however, the diaphragm and the muscle of the chest wall could still move during tidal respiration and cough. The accuracy of the augmented image relies on the immobilization of the patient and the target organ, which ensures that the region of interest is unchanged at the time of the first CBCT scan and during the following real-time fluoroscopy. Compared to light sedation, ETGA with a muscle relaxant immobilizing the patient yielded better image quality of the intraoperative CBCT scans (Supplementary Material, Fig. S1). During ETGA, respiration driven by the ventilator can still cause passive motion of the diaphragm, and sometimes patients also cough during the procedure when the dose of muscle relaxant declines; however, ETGA is still preferable for AFB localization. Another benefit of performing bronchoscopic procedures in ETGA is that the optic fibre can pass through the endotracheal tube into the bronchus, omitting the transoral or transnasal delivery of the fibre, which is irritative for patients and stressful for the operator. In addition, AFB localization was previously performed as a separate procedure in an angiography room, with a relatively longer postoperative stay (median: 4 days) and time at risk (median: 16.4 h) from localization to surgery [24]. In the recent series of the AFB procedure, localization and surgery were performed consecutively in the same suite, thus preventing the risk.

Compared to conventional multidetector CT, CBCT devices have a longer acquisition time, ranging from 5.4 to 40 s, which is long enough for the occurrence of motion artefacts caused by patient movements [27]. In our previous cohort of AFB localization, the patients received the first CBCT scan with voluntary breath holding when fully awake, but a confirmation scan was performed when the patient was under sedation and might not be able to hold their breath during the CBCT scan, which could generate motion artefacts that can interfere with the recognition of the lesion, particularly for ground-glass lesions. In this series, the condition of general anaesthesia prevented the generation of motion artefacts, which yielded better image quality of CBCT confirmation. However, recognition of the target lesion on the confirmation CBCT can still be challenging as, after the dye-spraying catheter moves through the endobronchial pathway, a small haemorrhage or focal atelectasis might occur, blurring the image, and the dye-mixed contrast agent can mask the target lesion on the CBCT images. Therefore, we adopted an image fusion technique to help locate the lesion in the confirmation CBCT using the bony structures as the image georeferencing targets.

The strategy for bronchoscopic pleural dye marking has evolved from single dye markers to multiple markers [26, 28]. In the virtual bronchoscopy navigation-based marking technique, also known as the virtual-assisted lung mapping system [29, 30], a comprehensive endobronchial roadmap should be made prior to the marking procedure, which usually contains several planned marking sites to cover each target lesion. The AFB system provides an alternative to guide bronchoscopic marking with real-time fluoroscopic visualization of the target lesion, where the operator can repeatedly adjust the marking sites by checking the augmented fluoroscopy. Owing to the advantages of AFB, we opted to place the dye marker closest to the target [24]; however, our strategy also evolved to multiple markings for several reasons. First, we tried to reduce the repeated insertion of the catheter through the small bronchus to lower the risk of bleeding from the endobronchial orifice; therefore, our strategy changed such that once the inserted catheter tip reaches the pleura, and the reaching point is close to the target, we perform pleural marking at that point and then make pleural markings through the neighbouring orifices to surround the lesion with markers. Second, we adopted an ultrathin bronchoscope to find more distal bronchial orifices that could lead to more pleural sites for multiple dye markings. In this series, an average of 3 dye markers were used to cover a single target lesion. Third, we reduced the amount dye from 1 to 0.25 ml for each marker, because in the HOR setting, the dye area can be seen by thoracoscopy shortly after pleural injection (median preparation time for surgery: 24 min), and the dye would not become faint or invisible in such a short period. Importantly, a smaller amount of dye ensures that only a ‘dye-spot’, instead of a large area, is marked on the lung surface, which gives the exact location where the dye was injected and also provides authentic geometric information that can be constructed using multiple dye markers.

Several institutes have utilized HOR with a robotic C-arm CBCT system to perform single-stage image-guided VATS (iVATS) [17–20]; the details of their workflows are summarized in Table 4. Most iVATS teams used the transthoracic needle approach for the placement of fiducial markers or dye injections, and the mean localization time ranged from 12 to 35 min. A high percentage (89–100%) of wedge resection was completed as the final surgical procedure; however, the operation time varied between 36 and 115 min. Two of the transthoracic groups [18, 20] reported global HOR times of 227 min (with Artis zeego) and 208 min (with Artis pheno). In our study cohort, transbronchial localization using the AFB system demonstrated comparable results (localization/global HOR time: 35 min/187 min) in the workflow of single-stage iVATS; however, there was still a learning curve even for an already experienced team to perform AFB localization in the HOR (Supplementary Material, Fig. S2).

Limitations

The present study has several limitations. First, this was a retrospective, single-centre observational study with a limited number of cases. Second, we do not present no long-term results after single-stage image-guided surgery, even though most lesions were early-stage lung cancer or precancerous lesions. Third, our dye marking plans were not strictly made before the procedure, as in the virtual-assisted lung mapping system, including the number of dyes and the endobronchial route for each marking. We often modified the plans according to the intraprocedural findings of the augmented fluoroscopy; therefore, the success of localization was subject to operator decisions and not easily defined. Fourth, cases using microcoils, potentially related to more CBCT scans, fluoroscopy time, radiation dose, surgery time and global time, were not analysed separately.

AFB-VATS performed as a single-stage procedure in the HOR under general anaesthesia with an endotracheal tube is feasible and safe. It is a novel method of image-guided VATS, which is free from needle-related complications and patient discomfort caused by bronchoscopy. Further investigation and accumulation of additional cases are required to clarify the benefits of this workflow for the localization and resection of small lung nodules.

SUPPLEMENTARY MATERIAL

Supplementary material is available at EJCTS online.

ACKNOWLEDGEMENTS

The authors thank the Siemens Healthcare marketing manager Frank Chun-Hsien Wu, PhD, and the application specialist Maxwell Jiun-Yan Lin for their technical assistance with the ARTIS Pheno operation and image post-processing and Siemens Healthcare research scientist Shwetambara Malwade for her helpful advice on revising the article.

Funding

This work was supported by a grant from the National Taiwan University Hospital, Hsin-Chu Branch, Taiwan (Grant Number 111-BIH008).

Conflict of interest: none declared.

Data availability

The authors this study confirm that the data generated during and/or analysed during the current study and the raw data that support the findings in this study are available from the corresponding author, upon reasonable request.

Author contributions

Shun-Mao Yang: Conceptualization; Data curation; Formal analysis; Funding acquisition; Investigation; Methodology; Project administration; Resources; Software; Validation; Visualization; Writing—original draft; Writing—review & editing. Wen-Yuan Chung: Data curation; Formal analysis; Project administration; Software; Visualization. Hang-Jang Ko: Conceptualization; Methodology; Project administration; Resources; Writing—review & editing. Lun-Che Chen: Data curation; Formal analysis; Investigation; Project administration; Validation; Writing—original draft. Ling-Kai Chang: Data curation; Formal analysis; Investigation; Methodology; Visualization; Writing—original draft. Hao-Chun Chang: Data curation; Formal analysis; Investigation; Software; Visualization; Writing—original draft. Shuenn-Wen Kuo: Conceptualization; Investigation; Methodology; Software; Supervision; Writing—review & editing. Ming-Chih Ho: Funding acquisition; Investigation; Supervision; Writing—review & editing.

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Clemens Aigner, Hiroshi Date, Haruhisa Matsuguma and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.

REFERENCES

ABBREVIATIONS

ABBREVIATIONS
 
• 3D

  Three-dimensional

 
• AFB

  Augmented fluoroscopic bronchoscopy

 
• CBCT

  Cone-beam computed tomography

 
• CT

  Computed tomography

 
• HOR

  Hybrid operating rooms

 
• ETGA

  Endotracheal tube intubation general anaesthesia

 
• IQR

  Interquartile range

 
• iVATS

  Image-guided VATS

 
• VAL-MAP

  Virtual-assisted lung mapping

 
• VATS

  Video-assisted thoracoscopic surgery