Arterial versus Venous Watershed Localization for Nonpalpable Pulmonary Nodules: A Retrospective Study

Summary

This study evaluates the watershed localization method (WALM) for intraoperative localization of nonpalpable pulmonary nodules. Both arterial and venous WALM using 3D reconstruction and indocyanine green (ICG) fluorescence are compared against CT-guided localization (CT-GL), showing shorter procedure time, fewer complications, and lower costs, but increased postoperative drainage and chest tube duration.

Abstract

Accurate localization of nonpalpable pulmonary nodules is critical for successful surgical resection. This study aimed to evaluate the feasibility and safety of the watershed localization method (WALM), a technique that uses three-dimensional reconstruction and temporary occlusion of watershed arteries or veins combined with indocyanine green (ICG) fluorescence staining for real-time intraoperative navigation. Clinical data were collected from patients who underwent video-assisted thoracoscopic pulmonary wedge resection with arterial-WALM (A-WALM), venous-WALM (V-WALM), or CT-guided localization (CT-GL) from October 2023 to October 2025. Patients were divided into three groups according to the localization method. Perioperative data were compared to evaluate localization efficacy. Both A-WALM and V-WALM were associated with shorter localization procedure time, lower incidence of localization-related complications, and reduced total hospitalization costs as compared with CT-GL. However, they were associated with greater postoperative drainage volume and longer chest tube indwelling time, with no significant differences in other indicators. When the pulmonary fissure is completely developed, the A-WALM approach may be better suited for nodules located in the posterior segment of the right upper lobe, right middle lobe, apicoposterior segment of the left upper lobe, or dorsal and anteromedial basal segments of either lower lobe; V-WALM may be preferable for nodules located in the anterior and lingular segments of the left lung and the posterolateral basal segment of both lungs, while either A-WALM or V-WALM is suitable for nodules in the apical and anterior segments of the right upper lobe. When the pulmonary fissure is incompletely developed, V-WALM may be preferred for localizing nodules in the right middle lobe and apicoposterior segment of the left upper lobe. In conclusion, both A-WALM and V-WALM appear to be feasible intraoperative localization alternatives to CT-GL in selected patients with nonpalpable pulmonary nodules, although they are associated with increased postoperative drainage and longer chest tube duration.

Introduction

With the increasingly widespread application of low-dose computed tomography (LDCT) in the early screening and diagnosis of pulmonary nodules, the detection rate of early-stage lung cancer has been significantly improved¹. Pulmonary wedge resection constitutes one of the most commonly employed surgical procedures for early-stage lung cancer, and the accurate localization of pulmonary nodules directly determines the success of the operation². Currently, CT-guided localization (CT-GL) is the commonly used clinical localization method. However, it is associated with various complications, including dislodgement, pneumothorax, hemothorax, pleural reactions, and even rare but life-threatening events such as air embolism. Furthermore, the success rate of CT-GL is strongly influenced by the location of pulmonary nodules; for example, the puncture path is often obstructed by structures such as the great vessels of the heart, scapulae, and ribs. Other methods, such as electromagnetic bronchoscopic navigation localization, are difficult to popularize due to drawbacks such as high cost and complex operation^3,4. Thus, exploring a simple, efficient localization method with minimal complications remains one of the urgent issues to be addressed in the management of early-stage lung cancer.

The watershed localization method (WALM) is a fluorescence-based technique that uses the concept of pulmonary vascular territories. The boundary between two adjacent vascular territories is termed the "watershed." By temporarily occluding the segmental artery or vein supplying the nodule-bearing area and injecting indocyanine green (ICG) intravenously, the occluded territory remains unstained while the surrounding lung fluoresces, creating a visible boundary on the lung surface. This allows precise wedge resection without preoperative puncture, avoiding radiation exposure and puncture-related complications. Against this backdrop, Chu et al. proposed the WALM, which uses three-dimensional (3D) reconstruction technology for pulmonary nodule localization⁵. This method enables clear visualization of key structures, including pulmonary segments, pulmonary arteries, pulmonary veins, and bronchi; facilitates real-time intraoperative localization; preserves more healthy lung tissues; and reduces the physical, mental, and economic burdens on patients⁵. Nevertheless, there is currently no consensus on whether WALM should be implemented as the arterial-WALM (A-WALM) or venous-WALM (V-WALM)^6,7.

Therefore, this study aimed to further elucidate the advantages of WALM over CT-GL and to systematically analyze the strengths, limitations, and optimal selection criteria for A-WALM and V-WALM in the intraoperative localization of pulmonary nodules. The completion of this study will be of significant value in formulating personalized localization and surgical plans for pulmonary nodules and will provide a further theoretical basis for the application of WALM in intraoperative localization of pulmonary nodules.

Protocol

This retrospective study was conducted in accordance with the Declaration of Helsinki (revised in 2013) and was approved by the Medical Ethics Committee of The Affiliated People’s Hospital of Ningbo University (Approval Number: 2025-135). All participants provided written informed consent prior to enrollment. The study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2500115862). All procedures involving human participants were performed in compliance with institutional guidelines.

Study design and patient selection
Clinical data were collected from patients who underwent video-assisted thoracoscopic pulmonary wedge resection with A-WALM, V-WALM, or CT-GL localization at the Department of Cardiothoracic Surgery, The Affiliated People's Hospital of Ningbo University, between October 1, 2023, and October 1, 2025. The inclusion criteria were as follows: (1) a pulmonary nodule measuring 8–20 mm in diameter located within the peripheral one-third of the lung field; (2) preoperative biopsy demonstrating preinvasive lesions or a ground-glass opacity (GGO) component ≥ 50%; (3) availability of high-quality chest computed tomography (CT) images suitable for accurate three-dimensional (3D) reconstruction; and (4) a clear indication for wedge resection without surgical contraindications. The exclusion criteria were: (1) a history of pneumoconiosis, tuberculosis, chronic obstructive pulmonary disease (COPD), or other significant pulmonary comorbidities; (2) allergy to iodine contrast agents; (3) a requirement for segmentectomy or lobectomy; (4) previous ipsilateral lung surgery; or (5) inability to tolerate surgery.

The patients were assigned to the A-WALM, V-WALM, or CT-GL group according to the localization method used. Propensity score matching (PSM) was performed to minimize potential confounding bias. A total of 148 patients were included in the study. After PSM, the A-WALM, V-WALM, and CT-GL groups comprised 48, 53, and 47 patients, respectively (Table 1). All covariates achieved adequate balance after matching, with standardized mean differences (SMDs) below 0.1 for all variables (P > 0.05; Table 1).

The choice of localization method (A-WALM, V-WALM, or CT-GL) was determined jointly by the surgical team based on preoperative 3D reconstruction findings, nodule location, pulmonary fissure completeness, vascular anatomy, and the feasibility of CT-guided puncture. The final decision was reached through multidisciplinary discussion and documented in the medical records. Surgeon preference and patient willingness were also considered, and all decisions were made before surgery.

Preoperative 3D reconstruction
Thin-section chest CT images (slice thickness, 1 mm) were acquired during end-inspiratory breath-hold. The Digital Imaging and Communications in Medicine (DICOM) data were imported into the Imaging Analysis System. Three-dimensional (3D) models were generated using automatic segmentation followed by manual correction to reconstruct the pulmonary arteries, veins, and bronchial tree. In cases with anatomical variations, the preoperative 3D model was used to guide surgical dissection planning. The segmental pulmonary artery within the nodule's watershed region was designated as the target vessel for A-WALM, whereas the corresponding segmental pulmonary vein was selected as the target vessel for V-WALM. Watershed regions were reconstructed to simulate reverse staining on the lung surface following peripheral indocyanine green (ICG) injection after temporary occlusion of the target vessel (Figure 1A1,A2,B1,B2).

CT-Guided Localization (CT-GL)
Pulmonary nodules in the CT-GL group were localized preoperatively using repeated CT-guided fine-needle puncture (Figure 1C1–C4).

Surgical procedure
Video-assisted thoracoscopic surgery was performed using the 3D fluorescence thoracoscopy system. The pre-identified watershed vessels were dissected and isolated, after which the target vessel was temporarily occluded using either a bulldog clamp or a 7-0 silk suture. Within 10 s of vessel occlusion, 3 mL of ICG solution (2.5 mg/mL; total dose, 7.5 mg) was injected through a peripheral vein. The boundary between the stained and unstained lung tissue was then marked with an electrosurgical knife. The vessel occlusion was typically maintained for 1–2 min. If the fluorescence staining was inadequate, the clamp was released for 3–5 min before repeating the ICG injection, with a maximum of two repeat injections. After the boundary had been marked, the clamp or suture was removed.

Wedge resection was subsequently performed using a linear stapler while ensuring adequate surgical margins (Figure 1A3–A5,B3–B5). In the CT-GL group, wedge resection was performed according to the preoperative localization needle position (Figure 1C5).

Outcome measures
The primary localization-related outcomes included technical localization success, initial wedge resection success, and the final R0 resection rate. Technical localization success was defined as successful completion of the assigned localization procedure without immediate failure requiring abandonment of the assigned method, including successful vessel occlusion with adequate fluorescence staining for WALM or successful marker placement at the target site for CT-GL. Initial wedge resection success was defined as achieving an R0 resection (microscopically negative margins) following the first wedge resection without requiring additional resection, and corresponded to the localization success rate reported as the primary outcome of this study. The final R0 resection rate was defined as the achievement of R0 resection after all remedial procedures, including extended wedge resection, conversion to segmental localization, or repeat puncture localization, when the initial wedge resection was unsuccessful.

Secondary outcomes included localization procedure time (defined as the duration from initial vessel dissection to complete boundary visualization for WALM and from the start of CT scanning to successful marker placement for CT-GL), total postoperative drainage volume, chest tube indwelling time, surgical margin distance, hospital stay, total hospitalization costs (including localization-related expenses, surgical fees, and postoperative care), localization-associated complications (pain, pneumothorax, marker displacement, hemorrhage, and prolonged air leak lasting > 5 days), changes in localization strategy due to intraoperative difficulty, vessel identification difficulty (rated by the operating surgeon as easy, moderate, or difficult) and its association with incomplete pulmonary fissures, and pathological findings.

Statistical analysis
Continuous variables were first evaluated for normality using the Shapiro–Wilk test. Variables meeting the assumption of normality are presented as mean ± standard deviation (SD) and were analyzed by one-way analysis of variance (ANOVA), with Bonferroni-adjusted post hoc comparisons applied where appropriate. Variables that were not normally distributed were compared using the Kruskal–Wallis H test, followed by pairwise Mann–Whitney U tests with Bonferroni correction. Differences in categorical variables were assessed using the χ² test. To determine whether the primary findings remained independent of important clinical factors, additional multivariable analyses were performed using generalized linear models and logistic regression, incorporating nodule-to-pleura distance, nodule location, and operating surgeon as covariates.

Given the retrospective, non-randomized study design, propensity score matching (PSM) was used to improve the comparability of the three treatment groups. A logistic regression model was constructed to generate propensity scores, with localization technique (A-WALM, V-WALM, or CT-GL) specified as the dependent variable and age, sex, body mass index, smoking history, nodule diameter, nodule-to-pleura distance, nodule location, pulmonary fissure completeness, and Charlson Comorbidity Index entered as matching variables. Patients were matched in a 1:1 ratio using nearest-neighbor matching without replacement, with a caliper width equal to 0.2 times the standard deviation of the logit-transformed propensity score. The success of the matching procedure was evaluated using standardized mean differences (SMDs), with values below 0.1 indicating satisfactory balance between groups. The number of patients included before and after matching was recorded for each study group.

Results

Demographic characteristics and nodule distribution among the groups
There were no significant differences in clinical characteristics, pulmonary nodule features, or nodule distributions among the three groups. All the enrolled patients successfully underwent wedge resection for solitary pulmonary nodules with adequate surgical margins (≥2 cm or ≥maximum tumor diameter). No ICG-related complications or perioperative mortality were observed. All 148 patients ultimately achieved final R0 resection afte...

Discussion

The widespread use of low-dose CT has increased early-stage lung cancer detection, with GGO as a predominant imaging finding^8,9. The 3D reconstruction technology has now been widely applied in preoperative planning for lung cancer treatment, providing high-quality digital models as references for pulmonary wedge resection^10,11,12. In addition, the method of visualizing t...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
7?0 silk suture	Ethicon (or local supplier)	Not available	Not available
Bulldog clamp	Medline (or local supplier)	Not available	Not available
Indocyanine green (ICG)	Generic (e.g., Yichuang Pharmaceutical)	Not available	Not available
Linear stapler	Ethicon or Medtronic	Not available	Not available
SPSS software	IBM Corp., Armonk, NY, USA	Version 26.0	RRID: SCR_002865
Storz IMAGE1 S 3D fluorescence system	Karl Storz SE&Co.KG, Tuttlingen, Germany	Not available	Not available
United Imaging Analysis System (3D reconstruction software)	United Imaging Healthcare, Shanghai, China	Not available	Not available