Retrospective comparison of three-dimensional computed tomography bronchography and angiography-assisted indocyanine green reverse staining versus modified inflation-deflation in robotic-assisted thoracoscopic segmentectomy

Introduction

Lung cancer is the most common malignant tumor worldwide and the leading cause of cancer-related deaths (1), with its treatment receiving sustained attention. Surgery has long been an indispensable component in lung cancer treatment. Recent studies have shown that compared with lobectomy, anatomical segmentectomy can achieve similar efficacy to lobectomy in patients with peripheral non-small-cell lung cancer (NSCLC) whose tumor diameter is ≤2 cm and the proportion of solid components is less than 50%, and the overall survival of patients is not inferior to that of lobectomy (2). The guidelines of the National Comprehensive Cancer Network (NCCN) also recommend that segmentectomy is feasible for early-stage lung cancer with a maximum tumor diameter ≤2 cm and a ground-glass component ≥50%. In recent years, with the popularization of computed tomography (CT) screening and the advancement of diagnostic methods, the detection rate of small-sized NSCLC has increased (3,4). Meanwhile, lung cancer patients tend to be younger, and the demand for preserving healthy lung tissue and achieving precise tumor resection is increasing. Anatomical segmentectomy has gradually become the preferred surgical method for patients with early-stage lung cancer due to its advantages, such as minimal trauma, rapid postoperative recovery, and better preservation of lung function.

The key to the success of anatomical segmentectomy lies in the accurate identification of intersegmental boundaries during the operation. However, there are no obvious anatomical boundaries between lung segments. During anatomical segmentectomy, it is particularly important to accurately distinguish the lung segments that need to be resected and those that need to be preserved. Common methods include the inflation-deflation method (5-7), selective segmental inflation (8), bronchial dye injection (9,10), etc. However, due to the existence of Kohn pores, these methods have the disadvantage of inflating or staining adjacent areas. Especially in patients with emphysema, the identification of intersegmental planes is particularly difficult. Moreover, both the inflation-deflation method and selective segmental inflation have problems such as obscuring the surgical field when the lungs are inflated, reducing the surgical operation space, long waiting time, and poor display of intersegmental planes, which bring certain difficulties to the operation. Intravenous injection of ICG under near-infrared fluorescence imaging is another effective method to display the target lung segments (11-15). Because it does not require inflation of the lungs and can quickly and easily identify the target lung segments in a narrow field of view, this technology is gradually being applied in clinical practice.

In addition, with the development of technology and the improvement of patients’ requirements for quality of life, robotic-assisted thoracoscopic surgery (RATS) has gradually become a new trend in lung cancer treatment due to its advantages, such as minimal trauma, rapid recovery, fewer complications, and more thorough lymph node dissection (16,17). Moreover, the robotic system can switch to fluorescence mode with one click, clearly displaying the lung segments to be resected after ICG injection in a short time. At the same time, the development of three-dimensional CT bronchography and angiography (3D-CTBA) technology has facilitated the accurate identification of anatomical structures. 3D reconstructed images can show the tumor in the target lung segment and confirm the bronchial and vascular anatomical structures, thereby formulating the best surgical plan. However, there are few clinical studies on preoperative 3D-CTBA combined with ICG reverse staining in RATS.

Therefore, we conducted a retrospective analysis of patients in Jinling Hospital Affiliated to Nanjing University who underwent RATS segmentectomy using 3D-CTBA combined with ICG reverse staining and the modified inflation-deflation method to determine intersegmental boundaries, evaluate their perioperative surgical outcomes, and explore the effectiveness and feasibility of this method. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2602/rc).

Methods

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Institutional Review Board of the Jinling Hospital (No. 2024DZKY-007-01) and individual consent for this retrospective analysis was waived.

Patient selection and inclusion criteria

We reviewed the data of 117 consecutive patients who underwent RATS segmentectomy in the Department of Thoracic Surgery, Jinling Hospital Affiliated to Nanjing University, between September 2022 and November 2024, all of whom received preoperative 3D-CTBA reconstruction for surgical planning. Among them, 57 cases used the ICG reverse staining method, and 60 cases used the modified inflation-deflation method. The modified inflation-deflation group consisted of consecutive patients who underwent RATS segmentectomy between September 2022 and April 2024, during which time the modified inflation-deflation method was the standard technique at our institution. The ICG group comprised consecutive patients treated between May 2024 and November 2024, after the introduction of intravenous ICG fluorescence imaging for RATS segmentectomy. Diagnostic and clinical information was collected by reviewing patients’ medical records. The inclusion criteria for patients were as follows: (I) tumor diameter less than 2 cm; and (II) ground-glass opacity component on CT of 50% or more. Exclusion criteria included: (I) tumor larger than 2 cm; (II) allergy to indocyanine green (ICG); (III) poor cardiac or pulmonary function unable to tolerate surgery; and (IV) distant metastasis of the tumor.

Patient demographic and clinical characteristics

Demographic and clinical characteristics included age, gender, body mass index, and underlying diseases such as hypertension, diabetes, and coronary heart disease. Tumor-related data included tumor location, pathological type, size, and staging. Surgery-related data included total operation time, intraoperative blood loss, number of lymph nodes dissected, chest tube placement time, postoperative hospital stay, and complications.

3D CT angiography and tracheography

All patients underwent preoperative high-resolution CT of the chest with a slice interval of 1 mm. We used the DeepMind Medical 3D Reconstruction Visualization System to perform 3D modeling of these images (Figure 1), observed the distances between the lesion site and the corresponding segmental bronchi, pulmonary arteries, and veins, and planned specific surgical procedures. All preoperatively planned segmental lung resections ensured that the surgical margin (the minimum distance from the lesion to the intersegmental boundary) was at least 2 cm.

Figure 1 Schematic diagram of preoperative chest CT and 3D reconstruction images. (A) Chest CT scan showing the pulmonary nodule located in the apical segment of the right upper lobe. The blue arrow indicates the pulmonary nodule. (B) 3D reconstruction of the bronchus. (C,D) The 3D reconstruction images of arteries and veins were respectively presented. 3D, three-dimensional; CT, computed tomography.

Surgical methods

All patients were placed in the lateral decubitus position on the healthy side, and the surgery was performed by the same surgeon using the Da Vinci Si system (Intuitive Surgical, Sunnyvale, CA, USA). This robotic system requires the use of one 12 mm Trocar as the camera port and two 8 mm Trocars as the operating ports: a 12 mm Trocar was inserted at the 7^th intercostal space (midaxillary line). Subsequently, two 8 mm Trocars were inserted at the 7^th intercostal space (posterior axillary line) and the 5^th intercostal space (anterior axillary line), respectively, serving as the first and second operating ports. Additionally, a 12 mm Trocar was inserted at the 9^th intercostal space (posterior axillary line) as the assistant’s operating port (Figure 2). Throughout the entire surgical procedure, the patient’s thoracic cavity remained in a closed environment, with continuous perfusion of carbon dioxide to maintain an intrathoracic pressure of 10 mmHg. The target segmental bronchus, target artery, and target vein were dissected step by step according to the preoperatively developed plan. For patients undergoing the modified inflation-deflation method, we first used pure oxygen to fully inflate the operative lung through controlled airway pressure at 30 cmH₂O. After the operative lung was completely inflated, single-lung ventilation on the healthy side was resumed. Once an irregular arc-shaped boundary naturally appeared between the deflated preserved lung segment and the inflated target lung segment, an electrocoagulation hook was used to mark the lung segment boundary on the lung surface. The time of intersegmental plane display is defined as the interval from the initiation of single-lung ventilation on the healthy side (following complete inflation of the operative lung) to the point at which the irregular arcuate boundary between the inflated target segment and the deflated residual segment becomes distinct, stable, and amenable to marking with an electrocoagulation hook. For patients undergoing the ICG reverse staining method, we directly administered an intravenous bolus of ICG (25 mg ICG dissolved in 10 mL physiological saline). After the intravenous injection was completed, the robotic camera was adjusted to the fluorescence imaging mode. At this point, the target lung segment showed no fluorescence under the fluorescence mode, while the remaining parts appeared fluorescent green. The boundary of the fluorescence on the visceral pleura was marked by cauterization, and then the target lung segment was completely resected along the mark using an endoscopic cutting stapler (Figure 3). The intersegmental plane display time is defined as the interval from the initiation of intravenous ICG injection to the point at which the non-fluorescent target segment and the fluorescence-normal lung tissue develop a distinct, continuous boundary on the visceral pleura and become amenable to marking via cauterization. All segmental plane display times were evaluated by two senior attending physicians familiar with the predefined display time endpoints and confirmed by reviewing surgical videos, and the assessors were not blinded. After removing the specimen, water was injected into the thoracic cavity and the lung was re-inflated to check for air leakage and bleeding. If air leakage or bleeding was observed, electrocoagulation, cauterization, or suturing was performed. After repeatedly confirming that there was no significant air leakage or bleeding, a 20-Fr chest tube was placed through the camera port.

Figure 2 Incision site selection for robotic surgery. The camera port is located at the intersection of the 7^th intercostal space and the midaxillary line. The 1^st and 2^nd working ports are placed at the intersection of the 7^th intercostal space and the posterolateral axillary line and the intersection of the 5^th intercostal space and the anterolateral axillary line, respectively. The assistant port is located at the intersection of the 9^th intercostal space and the posterolateral axillary line.

Figure 3 Schematic diagram illustrating the comparison of surgical outcomes with ICG versus the modified inflation-deflation technique. (A) Lung tissue without ICG injection. (B) Clear intersegmental plane visualized after ICG injection, marked by electrocautery hook ablation. (C) Lesion resection performed according to the ablated marks. (D) Full re-expansion of the operated lung achieved by the modified inflation-deflation method. (E) Intersegmental boundary exposed using the modified inflation-deflation method. (F) Lesion resection performed based on the intersegmental boundary. ICG, indocyanine green.

Lymph node dissection

(I) Each patient underwent dissection of at least three groups of mediastinal lymph nodes. (II) For patients with left lung tumors, dissection of lymph node groups 5, 6, and 7 was mandatory; for patients with right lung tumors, dissection of lymph node groups 2R, 4R, and 7 was mandatory. Notably, patients with inferior lung tumors were required to undergo dissection of lymph node groups 7 and 9.

Postoperative management and pain assessment

The patient was transferred to the intensive care unit (ICU) immediately postoperatively. The patient was then moved to a general ward on the second postoperative day, with no significant abnormalities or complications noted. For initial postoperative pain management, a patient-controlled analgesia (PCA) pump was utilized (including opioid analgesic, e.g., sufentanil; nonsteroidal analgesic, e.g., flurbiprofen axetil; antiemetic, e.g., granisetron). If the patient’s Visual Analogue Scale (VAS) pain score exceeds 3 points, oral or intravenous analgesics should be administered as indicated to provide additional pain relief. The primary nurse performed daily pain scoring via the VAS at 08:00 each morning, and this assessment was continued until the patient’s discharge.

Statistical analyses

All data were recorded using Microsoft Office Excel 2019. Data were analyzed using SPSS 24.0. Categorical variables are summarized as numbers and percentages and compared using the Chi-squared test or Fisher’s exact test as appropriate. Continuous variables were assessed for distribution. Variables approximating normality are reported as mean ± standard deviation (SD) and compared using Student’s t-test, and skewed variables are reported as median (interquartile range) and compared using the Wilcoxon rank-sum test. All tests were two-tailed, and a P value less than 0.05 was considered statistically significant.

Results

Comparison of basic patient characteristics between the two groups

A total of 117 patients were included in this study, with 54 males (46.15%) and 63 females (53.85%). There were no statistically significant differences in the basic characteristics [average age (P=0.45), body mass index (P=0.19), smoking history (P=0.89), alcohol (P=0.050), lung function (P=0.30), underlying diseases, tumor size (P=0.13), and location (P=0.11)] between the two groups (Table 1).

Comparison of surgical conditions and perioperative indicators between the two groups

All patients achieved R0 resection. There was no statistically significant difference in postoperative pathology between the two groups (P=0.49). Among them, 4 patients in the ICG group had postoperative pathological findings indicating visceral pleural invasion (VPI), and 1 patient had lymphovascular invasion (LVI) (Table 2). For the primary outcome measures of this study—the time for displaying intersegmental boundaries and the operative time—the ICG group was significantly less than the modified inflation-deflation group, with statistically significant differences. Additionally, intraoperative blood loss was markedly less in the ICG group compared with the modified inflation-deflation group, with statistically significant differences. Nevertheless, no statistically significant differences were noted between the two groups in terms of secondary outcome measures, including the number of lymph nodes (P=0.32), surgical margin distance (P=0.45), chest tube indwelling time (P>0.99), and postoperative hospital stay (P=0.56) (Table 3).

Discussion

Since the publication of a randomized trial in 1995, lobectomy has been recommended for clinical stage IA NSCLC and has long been used as the gold standard (18). With the continuous advancement of related technologies, especially the widespread application of CT, the epidemiological characteristics of lung cancer have undergone significant changes, and the detection rate of early-stage lung cancer has greatly increased (19). Patients also tend to be younger, so the surgical treatment strategies for early-stage lung cancer are gradually changing. Relevant studies have confirmed that compared with lobectomy, anatomical segmentectomy not only has a similar survival rate (20,21), but also can preserve more lung function and bring a better prognosis (22). However, anatomical segmentectomy has stricter requirements for the precise identification of blood vessels and bronchi, and the difficulty of operation technology has increased accordingly. RATS, with its significant advantages such as excellent flexibility, stable vision, and high-precision instrument control, has been increasingly widely used in anatomical segmentectomy.

In segmental lung resection, determining the intersegmental plane is the most critical step in the operation. According to published evidence, the main methods for accurately identifying the intersegmental plane include the inflation-deflation technique, systemic injection of ICG, selective resected segmental inflation, and injection of endobronchial dye (23). The modified inflation-deflation method and intravenous injection of ICG are currently the two main clinical methods for determining the intersegmental plane. Compared with intravenous injection of ICG, the modified inflation-deflation method requires the use of pure oxygen during the operation to fully re-expand the collapsed lung and then resume one-lung ventilation, keeping the target lung segment in an inflated state, thereby delineating the intersegmental plane with the adjacent collapsed segment. This not only greatly reduces the surgical operating space and field of view but also prolongs the operation time. In addition, Li et al. reported that the division of the interface may be inaccurate for patients with severe emphysema or pulmonary fibrosis (24).

Studies have indicated that intravenous injection of ICG can accurately display intersegmental boundaries, reduce surgical time, and lower the incidence of related complications. This is particularly true for patients with poorly developed pulmonary fissures and severe pleural adhesions, where intravenous ICG can improve the safety of the surgery (11-15). However, the complex anatomical structures of pulmonary segmental bronchi and blood vessels remain a significant challenge (25). Therefore, in this study, we employed 3D-CTBA reconstruction before surgery to visualize intrapulmonary tumors and their target segmental blood vessels and bronchi, in order to formulate the optimal surgical plan. Additionally, based on the 3D-CTBA reconstruction results, we precisely transected the target segmental artery, target segmental vein, and target segmental bronchus. Subsequently, ICG was intravenously injected, and the fluorescence mode of the robotic system could quickly and clearly display the intersegmental boundaries. The target pulmonary segment, due to the absence of blood perfusion, does not emit fluorescence and remains dark, while the rest of the lung, with blood flow, exhibits a fluorescent green color, thereby clearly showing the intersegmental boundaries. The results of this study demonstrated that preoperative 3D-CTBA reconstruction combined with intraoperative intravenous injection of ICG can accurately and rapidly display intersegmental boundaries, thereby significantly reducing surgical time. Moreover, compared with the modified inflation-deflation method, the intersegmental boundaries are clearer, and a sufficient safe margin distance can be ensured, meeting oncological requirements. Compared with the modified inflation-deflation group, the proportion of patients in the ICG group who required medication for postoperative pain was lower. This may be related to the fact that the resected lung tissue in the modified inflation-deflation group does not collapse, resulting in relatively larger specimens, which may cause traction on the incision or even require incision enlargement during specimen retrieval. Despite the positive outcomes of this study, there are certain limitations. Firstly, this is a single-center retrospective study, which may have selection bias, thereby reducing the generalizability of the results. Secondly, the number of cases is relatively small, and the long-term follow-up of patients is insufficient, making it impossible to analyze the long-term oncological outcomes related to these methods. It is hoped that in future studies, the number of cases will be increased, and the long-term effects on patients will be statistically analyzed to obtain more accurate results.

Conclusions

In this single-center retrospective cohort, 3D-CTBA reconstruction combined with ICG reverse staining is a safe and feasible strategy for intersegmental plane delineation in RATS segmental lung resection. Compared with the modified inflation-deflation method, it exhibits favorable perioperative outcomes, including shorter intersegmental delineation time, reduced intraoperative blood loss, and shorter operative time. These comparative findings provide clinical reference for intersegmental plane identification in RATS segmentectomy, while long-term oncological outcomes and generalizability require further prospective validation.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2602/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2602/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2602/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2602/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 and its subsequent amendments. This study was approved by the Institutional Review Board of the Jinling Hospital (No. 2024DZKY-007-01) 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/.

References

1. Filho AM, Laversanne M, Ferlay J, et al. The GLOBOCAN 2022 cancer estimates: Data sources, methods, and a snapshot of the cancer burden worldwide. Int J Cancer 2025;156:1336-46. [Crossref] [PubMed]
2. Nakamura K, Saji H, Nakajima R, et al. A phase III randomized trial of lobectomy versus limited resection for small-sized peripheral non-small cell lung cancer (JCOG0802/WJOG4607L). Jpn J Clin Oncol 2010;40:271-4. [Crossref] [PubMed]
3. Darling GE, Tammemägi MC, Schmidt H, et al. Organized Lung Cancer Screening Pilot: Informing a Province-Wide Program in Ontario, Canada. Ann Thorac Surg 2021;111:1805-11. [Crossref] [PubMed]
4. Oliver AL. Lung Cancer: Epidemiology and Screening. Surg Clin North Am 2022;102:335-44. [Crossref] [PubMed]
5. Endoh M, Oizumi H, Kato H, et al. Determination of the intersegmental plane using the slip-knot method. J Thorac Dis 2018;10:S1222-8. [Crossref] [PubMed]
6. Kamiyoshihara M, Kakegawa S, Morishita Y. Convenient and improved method to distinguish the intersegmental plane in pulmonary segmentectomy using a butterfly needle. Ann Thorac Surg 2007;83:1913-4. [Crossref] [PubMed]
7. Kamiyoshihara M, Kakegawa S, Ibe T, et al. Butterfly-needle video-assisted thoracoscopic segmentectomy: a retrospective review and technique in detail. Innovations (Phila) 2009;4:326-30. [Crossref] [PubMed]
8. Suzuki J, Oizumi H, Watanabe H, et al. Revaluation of a selected segmental insufflation technique in total thoracoscopic lung segmentectomy. Interdiscip Cardiovasc Thorac Surg 2023;36:ivad054. [Crossref] [PubMed]
9. Zhang Z, Liao Y, Ai B, et al. Methylene blue staining: a new technique for identifying intersegmental planes in anatomic segmentectomy. Ann Thorac Surg 2015;99:238-42. [Crossref] [PubMed]
10. Nex G, Schiavone M, De Palma A, et al. How to identify intersegmental planes in performing sublobar anatomical resections. J Thorac Dis 2020;12:3369-75. [Crossref] [PubMed]
11. Gurz S, Sullu Y, Tomak L, et al. Comparison of Margin Quality for Intersegmental Plan Identification in Pulmonary Segmentectomy. Medicina (Kaunas) 2025;61:535. [Crossref] [PubMed]
12. Ochi T, Sakairi Y, Sata Y, et al. Indocyanine green intravenous administration can more accurately identify the intersegmental plane than the inflation-deflation method in lung segmentectomy. PLoS One 2025;20:e0328362. [Crossref] [PubMed]
13. Guigard S, Triponez F, Bédat B, et al. Usefulness of near-infrared angiography for identifying the intersegmental plane and vascular supply during video-assisted thoracoscopic segmentectomy. Interact Cardiovasc Thorac Surg 2017;25:703-9. [Crossref] [PubMed]
14. Pischik VG, Kovalenko A. The role of indocyanine green fluorescence for intersegmental plane identification during video-assisted thoracoscopic surgery segmentectomies. J Thorac Dis 2018;10:S3704-11. [Crossref] [PubMed]
15. Pardolesi A, Veronesi G, Solli P, et al. Use of indocyanine green to facilitate intersegmental plane identification during robotic anatomic segmentectomy. J Thorac Cardiovasc Surg 2014;148:737-8. [Crossref] [PubMed]
16. Musgrove KA, Hayanga JA, Holmes SD, et al. Robotic Versus Video-Assisted Thoracoscopic Surgery Pulmonary Segmentectomy: A Cost Analysis. Innovations (Phila) 2018;13:338-43. [Crossref] [PubMed]
17. Ureña A, Moreno C, Macia I, et al. A Comparison of Total Thoracoscopic and Robotic Surgery for Lung Cancer Lymphadenectomy. Cancers (Basel) 2023;15:3442. [Crossref] [PubMed]
18. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995;60:615-22; discussion 622-3. [Crossref] [PubMed]
19. Usman Ali M, Miller J, Peirson L, et al. Screening for lung cancer: A systematic review and meta-analysis. Prev Med 2016;89:301-14. [Crossref] [PubMed]
20. Suzuki K, Saji H, Aokage K, et al. Comparison of pulmonary segmentectomy and lobectomy: Safety results of a randomized trial. J Thorac Cardiovasc Surg 2019;158:895-907. [Crossref] [PubMed]
21. Moon MH, Moon YK, Moon SW. Segmentectomy versus lobectomy in early non-small cell lung cancer of 2 cm or less in size: A population-based study. Respirology 2018;23:695-703. [Crossref] [PubMed]
22. Nomori H, Shiraishi A, Cong Y, et al. Differences in postoperative changes in pulmonary functions following segmentectomy compared with lobectomy. Eur J Cardiothorac Surg 2018;53:640-7. [Crossref] [PubMed]
23. Andolfi M, Potenza R, Seguin-Givelet A, et al. Identification of the intersegmental plane during thoracoscopic segmentectomy: state of the art. Interact Cardiovasc Thorac Surg 2020;30:329-36. [Crossref] [PubMed]
24. Li Y, Cao Y, Chen Y, et al. Comparison of watershed analysis with indocyanine green fluorescence staining and modified inflation-deflation method in single-port thoracoscopic complex pulmonary segmentectomy. J Thorac Dis 2024;16:7697-708. [Crossref] [PubMed]
25. Browne IL, Patel YS, Hanna NM, et al. Three-dimensional virtual lung reconstruction in robotic segmentectomy: A safety and feasibility trial. JTCVS Tech 2025;29:150-60. [Crossref] [PubMed]