Efficacy, safety and patient satisfaction of two-stage versus single-stage computed tomography guided localization and resection of pulmonary nodules

Introduction

Low-dose computed tomography (CT) has been increasingly utilized for lung cancer screening (1,2). There are 25% of Fleischner Society’s study subjects incidentally diagnosed with solitary pulmonary nodule (SPN) upon low-dose CT screening. Pulmonary nodules with malignant potential warrant referral to thoracic surgeons for surgical biopsy and resection (3). Clinical localization of these SPNs remains as the major challenge for video-assisted thoracoscopic surgical (VATS) resection. The difficult visualization and palpation of small SPN, especially ground glass opacity (GGO) render conscientious pre-operative localization to expedite intra-operative identification. Traditional two-stage localization method including indocyanine green (ICG), hookwire and/or methylene blue is performed by intervention radiologists one day prior to or on the same day of the planned operation (4).

The traditional two-stage method is however labor and time intensive in nature. It demands transport and coordination between the radiology and surgical departments. The significant time interval between localization and surgical resection in two-stage method is also associated with a higher risk of marker failure (e.g., dye fading), patient psychological distress and complications [e.g., pneumothorax, hemothorax, etc. (5)], which increase morbidity while decreasing the chances of a successful resection.

The emergence of hybrid operating theatre has pioneered single-stage localization and resection of SPN in modern thoracic surgery. Thoracic surgeons are able to localize and resect SPN with intraoperative CT simultaneously in a single theater section. Such advance improves clinical workflow by decreasing the time required for inter-disciplinary coordination and minimizing time-related risks such as increasing pneumothorax and untreated hemothorax. (i.e., time lag between localization and resection) (6,7). However, research with a direct comparison of the overall patient experience is lacking. This study therefore aims to analyze the efficacy, safety and patient satisfaction of two-stage versus single-stage CT guided localization and resection of pulmonary nodules. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-303/rc).

Methods

Study design

This is a retrospective, open-label single-center study conducted by the Department of Cardiothoracic Surgery of Queen Elizabeth Hospital, Hong Kong. Patients underwent single and two-stage resections of SPNs between 1 October 2021 and 30 June 2023 were identified and recruited as study subjects. Required data were extracted from Clinical Data Analysis and Reporting System (CDARS) and Clinical Management System (CMS). Clinical information was extracted from follow-up consultation notes, operation records and relevant clinical documentation.

Inclusion and exclusion criteria

Patients selected for localization and resection of SPNs between 1 October 2021 and 30 June 2023 were eligible and included as study participants. Patients excluded from the study included those who encountered unexpected machine failure during localization, patients with nodule progression and patients with nodule regression and patients with nodule regression on preliminary CT who no longer required an operation.

Two-stage localization: pre-operative localization

In the two-stage localization arm, the patient received pre-operative CT scan at the radiology suite to determine the shortest safe localization trajectory between skin and target lesion by our interventional radiologist. Skin disinfection was carried out by standard aseptic technique and lignocaine was infiltrated into the intended entry site. Under CT guidance, a 22-G Franseen needle was advanced into the target lesion (Figure 1). After confirming that the location of the needle in relation to the target lesion was satisfactory, ICG mixed 1:9 with lipiodol was performed. After successful localization, the patient was transferred back to the wards and awaited surgical resection usually on the next day.

Figure 1 Percutaneous insertion of Franseen needle under hybrid theatre computed tomography guidance.

Single-stage localization: intra-operative localization in hybrid theatre

Single-stage localization requires the availability of a hybrid operation intra-operative C-arm with cone beam CT capabilities. Patient was put under general anaesthesia. Ventilation was stopped with a peak end expiratory pressure (PEEP) of 10 cmH₂O maintained briefly. Persistence of the lesion was confirmed with cone beam CT (Figure 2). A 22-G Franseen needle was introduced towards the lesion with the same ventilatory technique described above under cone beam CT guidance (Figure 1). Final needle position and pattern of lipiodol staining were confirmed after injection of the same ICG-lipiodol emulsion. Surgical resection was proceeded immediately in the same session after successful localization.

Figure 2 Pre and post indocyanine green localized lesion confirmation by cone beam computed tomography.

Definitive treatment

After successful localization, standard VATS sublobar or lobar resection was performed based on underlying pathology and the patient’s underlying lung function (Figures 3,4).

Figure 3 Visual confirmation of indocyanine green localized lesion on video assisted thoracoscopic surgery.

Figure 4 Side by side white light and infrared endoscopic following successful resection of solitary pulmonary nodule.

Study outcomes

Primary study outcome was the time required for lesion localization which was defined as the time from beginning to the end of lesion localization. Other secondary outcomes included the rate of successful lesion localization (i.e., number of successful intra-operative identification/total number of localizations done), total operative time (including localization for single-stage localization), localization time (for single-stage localization), complication rate including pneumothorax, duration of hospital stay, 30-day readmission and mortality rate. Successful localization of target lesion was defined as the clear visualization of ICG staining of the target pulmonary parenchyma seen via infra-red endoscopic camera. Patient satisfaction was evaluated as a secondary outcome including mean total patient satisfaction score and mean patient pain score based on a modified version of a peer-reviewed questionnaire for patient satisfaction after receiving surgery (8). A numerical pain score scale from 1 being the most severe pain ever experienced to 10 being the least pain experienced was added to assess the perceived pain.

Statistical analysis

Study participants’ age and sex were collected for basic demographics analysis. Clinical parameters including lesion quantity, size, location, distance to pleura, depth-to-size ratio, morphological type on imaging, American Society of Anaesthesiologist (ASA) physical status classification, position for localization and localization technique were retrieved for general characterization. Time to treatment, localization time, at risk time between localization and surgery and its associated complications without surgical intervention (e.g., risk of dye fading/failure and developing pneumothorax or haemothorax), time between induction and skin incision, time from incision to completion of wedge, time from anaesthesia induction to completion of wedge, successful targeting rate, number of scans for localization and type of procedure for lesion resection were collected for outcome assessment. For safety assessment, post-procedural complication rate (e.g., pneumothorax and haemothorax), conversion to thoracotomy, localization failure rate, duration of post-operative hospital stay and post-discharge 30-day readmission rate were collected.

Categorical variables were analyzed with logistic regression and continuous variables with Poisson regression. Statistical analysis was performed with R-Studio.

Ethical concern

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by Kowloon Central Cluster Institutional Review Board (KC/KE-23-0112/ER-4) and individual consent for this retrospective analysis was waived. To protect patients’ privacy, all data were handled/stored/destructed according to Personal Data (Privacy) Ordinance and Hospital Authority Data Protection Policy. All data would be locked in cabinets where the department or ward keeps patients’ confidential information. Electronic data should be saved in secured computers of the hospital with restricted access. The protocol complies with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice (GCP).

Results

During the study period, 83 patients were identified and included in the study. All data within 30 days of operation were able to be retrieved for all 83 patients. Twenty-seven of them received single-stage localization and 56 patients underwent a two-stage procedure. There were no patients excluded from the study based on the pre-established exclusion criteria. Patient demographic and general clinical characteristics are stated in Table 1. Age distribution was similar from both arms. Overall, pre-operative CT revealed that the majority of 62 lesions (74.70%) were radiologically classified as GGO, whereas 21 (25.30%) were solid nodules. Mean size of pulmonary lesion on pre-op CT in both arms was 1.42 cm (interquartile range, 1–1.70 cm). The mean depth from pleura was 1.05 cm (interquartile range, 1–1.70 cm). No allergic reactions were noted as a result of injection of localization medium.

In single-stage group, majority of patients (19, 70.37%) were localized in lateral position. While 46 patients (82.14%) from the two-stage arm were performed in supine position. All patients received ICG dye localization, in addition, 6 patients (7.23%) required additional localization by hookwire. No significant differences in permeability and retention of ICG regardless of tumor type were noted.

Primary and secondary outcomes are summarized in Table 2. Operative time in the single-stage arm (mean: 188 min) was significantly longer compared to that of the two-stage group (mean: 172 min, P<0.001). Of note, total operative time included in the single-stage arm included localization, repositioning for VATS as well as lung resection. Mean localization time of single-stage arm was 34.33 min (interquartile range, 14.5–39 min). Localization times for the two-stage arm were not included as it did not impact operative time. All patients from both arms received successful localization and resection of lung nodules. All localization specimens yielded positive pathological results. There were no reported localization failures (e.g., dye spillage and fading). No side effects or allergic reactions were reported in both arms. No patient required conversion to a thoracotomy approach. Overall post-procedural pneumothorax rate was 16.9% with no significant intergroup differences identified with respect to the rate of post-procedural pneumothorax (P=0.25). Mean duration of hospital stays of single-stage and two-stage arms were 4.78 and 5.54 respectively (P=0.16). There was no statistically significant difference in duration of hospital stay, 30-day readmission and mortality.

Mean total patient satisfaction score was significantly higher in the single-stage group than that of the two-stage group (92 vs. 53, P=0.004). Patient-reported pain was better tolerated in the single-stage arm (mean: 8.8) vs. the two-stage arm (mean: 4.85, P=0.007).

Discussion

To our knowledge, this is the first study to include patient satisfaction and pain perceived in comparing two current approaches for localization and resection of small SPNs. Previous studies focused mainly on evaluating efficacy and safety of the two approaches with limited data on patients’ communication, satisfaction, pain control and overall experience (7,9). The identical successful lung nodule localization rates (i.e., 100% in the single-stage and two-stage arm) with a minor increase in mean operative time illustrated that intra-operative CT-guided approach is effectively identical to the conventional approach. An intra-operative setting with cone-beam CT has been proven to be able to accurately localize SPNs for resection (10). We also demonstrated no significant difference in complications and duration of hospital stay from both arms. We also investigated the position for localization, as patients who received localization in a lateral position required less effort to be repositioned for VATS. This is evidenced by our preference for lateral positioning for up to 70.4% of patients.

We also noted that significant procedural adjustments were required to perform localization successfully under general anesthesia. If ventilation was stopped without adequate PEEP support, atelectasis of the peripheral lung parenchyma may obscure small SPNs, rendering localization impossible. Furthermore, as the lesion may move up to 1 rib space between inspiration and expiration, maintaining the same level of PEEP is mandatory to ensure consistent lesion location for imaging and needle puncture. We found that stopping ventilation with a PEEP of 10 cmH₂O consistently yielded reproducible results and has since been incorporated into the departmental protocol.

To our knowledge, this study represents the first study which analyzed patient experience between those who receive single and two-stage localization. Our findings also demonstrated higher overall patient satisfaction in the single-stage arm which was evaluated in several aspects including: communication with healthcare staff, nursing care, decision making involvement and discharge planning. We postulate that since single-stage patients were only cared for by a single thoracic surgical team rather than being handed over back and forth to the interventional radiological team, this contributed to the better overall sense of control that the patient retained and the rapport built with the team.

Pain tolerance including subjective pain assessment was assessed in our study. Patients reported an overall better pain control in the single-stage localization arm compared to the two-stage arm. Although local anesthesia was used during two-stage localization, to some degree the sensation of pain was unavoidable, of which the patient had to bear until general anesthesia. Moreover, if hookwires were used, patients had to bear with the uncomfortable sensation of a penetrating foreign body in their chest until the operation. Overall, as both localization and surgical resection were performed under general anesthesia, this may explain why intra-operative localization and resection is superior in terms of patient satisfaction.

There are several limitations in this retrospective study. This is a single-center based study which inevitably limits the generalizability of our data. Secondly, patient allocation to both arms was not randomized due to the limited availability of hybrid theatre. Selection bias could have occurred as decision for SPN localization was made by thoracic surgeon alone rather than a multidisciplinary decision. Moreover, our study focused on evaluating percutaneous localizing approach and did not compare with non-percutaneous localization approaches (e.g., virtual bronchoscopy and electromagnetic navigation bronchoscopy). Future randomized controlled trial comparing efficacy and safety with the aforementioned approaches is required to justify selection of individualized localization modality of SPN before surgical resection.

The facility of hybrid operation theatre followed by single-stage localization has been only available in our center since October 2021. A previous study has demonstrated a significant learning curve in single-stage approach (11). With further optimization in team coordination, theatre adjustment and procedural techniques, we believe our team’s experience can be generalized to other centers at which the medical teams are contemplating on starting their own one-stop SPN localization and resection program. All ICG procedures were carried out as a pilot program by a consultant thoracic surgeon and a thoracic surgical resident without prior hands-on experience after consultation with interventional radiology. As such this study showed that the learning curve presented by intra-operative localization can be overcome by a dedicated team of surgeons without prior experience.

The enhancement in patient satisfaction and pain control did not result in apparent improvement (e.g., duration of hospital stay, procedural complications, readmission and mortality rate). Hence, clinical decision between single and two-stage localization options should be an individualized decision based on availability of hybrid theatre and team coordination.

Conclusions

Overall, single-stage intra-operative localization performed in hybrid theater is associated with a similar total operative time, higher overall patient satisfaction and better pain control when compared to the conventional approach. Future decisions on localization approaches should be based on surgeon preference and facility availability at a specific cardiothoracic center.

Acknowledgments

The authors would like to thank Mr. Geraint Chow for his support regarding statistical analysis used in this study.

Funding: The research project was authorized and supported by the Department of Cardiothoracic Surgery, Queen Elizabeth Hospital, Hong Kong. There was no commercial funding relationships to be declared.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-303/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-303/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-303/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-303/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by Kowloon Central Cluster Institutional Review Board (KC/KE-23-0112/ER-4) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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