Techniques to identify pulmonary nodules intraoperatively: narrative review on advances and clinical decision-making

Introduction

Lung cancer is the leading cause of cancer-related death in Canada and the United States, and the second most common cause of cancer death worldwide (1-3). This has led to major advancements in the detection, management and outcomes for this deadly disease (4). Recent lung cancer screening guidelines recommend chest computed tomography scans (CT-scans) for high-risk patients (3). This has led to an increase in the number of CT-scans performed and lung nodules detected. At the same time, this trend also affects other specialties, including the increase in CT-scans for staging of extrathoracic malignancies or to evaluate coronary artery disease and calcification. The increase in imaging is associated with an increase in the number of small undetermined pulmonary lesions (5,6), potentially representing early stage lung cancer. Current management of non-small cell lung cancer (NSCLC) includes resection (7-9), even for lesions that are sometimes too small for preoperative tissue diagnosis. A similar approach is applied to small indeterminate pulmonary nodules, where excisional biopsy often serves as the primary diagnostic and management strategy. As such, the standard of care for pulmonary nodules with high-risk features on imaging typically involves wedge resection for pathological evaluation.

Resection is therefore a key step in pulmonary cancer management. The recent standard of care involves minimally invasive resection via video-assisted thoracic surgery (VATS) (7,8,10). VATS improves patient recovery and reduces pain when compared to standard thoracotomy with no impact on oncologic outcomes (8,9). The use of thoracoscopic instruments unfortunately reduces tactile feedback, making the detection of small or deep pulmonary nodules difficult. This haptic feedback is also completely lost in robotic-assisted thoracic surgery (RATS) (11). The rising detection of pulmonary nodules has led to an increased number of ground-glass opacities (GGOs) requiring surgical management. These lesions are difficult to localize even for experienced surgeons. As nodules become smaller and less dense, manual palpation via minimally invasive techniques are no longer a reliable method for intraoperative localization. Consequently, a variety of localization techniques have been developed to assist thoracic surgeons to accurately identify and resect the targeted lesion.

There is currently no universally recommended standard for pre-operative or intraoperative localization of pulmonary nodules. Technique selection is influenced by patient characteristics, technical considerations, institutional resources, and local expertise. As a result, thoracic surgeons have variable exposure to nodule marking, and commonly used techniques have not been directly compared or validated leading to variability in practice and limited direct comparisons or validation across methods.

This narrative review synthesizes the existing literature on localization strategies highlighting success rates, accuracy, and complications while outlining the strengths and limitations of each technique. It identifies pivotal studies, compares findings from the largest series available, and examines feasibility of implementation across diverse clinical settings. Building on these insights, the review introduces a novel decision-making algorithm that incorporates key factors to support individualized and practical technique selection. The goal is to provide a resource to thoracic surgeons of the available options and support informed decision-making given the multiple techniques accessible. We present this article in accordance with the Narrative Review reporting checklist (available at https://vats.amegroups.com/article/view/10.21037/vats-25-23/rc).

Methods

A literature review was conducted using relevant keywords and MeSH terms, with no restrictions on study characteristics (Table 1). A search using the terms “pulmonary nodule” (AND) “localization” or “marking” was performed using the databases EMBASE and MEDLINE on April 3^rd, 2025; no time or language restriction was imposed to the search. Using the PubMed^® browser, the search was refined using the same MeSH terms. From this search, more than 80 different articles, published between 1990 and 2025, were selected based on the title and abstract, identifying different lung nodule localization techniques. Inclusion was based on date of publication, subjective quality assessment, clinical impact (as reflected by citations), and a description of the method. Studies focusing on rarely used or emerging techniques were included even if they lacked some of these features, given the limited available literature in certain areas. Articles were reviewed independently by authors (A.D. and A.W.) and using the identified techniques, further searches were conducted using a combination including the technique with (AND) “pulmonary nodules”. Literature identified was used for citation chaining to discern other relevant material. Citation chaining and additional search techniques were employed to ensure a comprehensive review. The content was overseen by thoracic surgeons at various stages of their careers.

Nodule localization techniques

Nodule palpation

Nodule palpation is the traditional way to identify pulmonary nodules intraoperatively. This technique does not require any additional equipment, no increased cost is associated with it and no additional training is required. Aside from potential trauma to the lung parenchyma, no significant complications are associated with nodule palpation. Surgeons use a variety of tools, from fingers to VATS instruments to probe and sweep the lung parenchyma. It was the eventual lack of sensitivity to detect small or deeper lung nodules that led to the development of more sophisticated lung nodule localization techniques.

When focusing on the reported literature, nodule palpation is a technique with a wide range of detection. Ichinose et al. (12) published a study in 2019 focusing on nodule identification via VATS. In a cohort of 229 patients, 267 nodules ranging from 3 to 15 mm were identified with VATS instruments and finger palpation, reporting a success and accuracy rate of 100%, and no complications. In comparison, studies focusing on perioperative localization of small nodules had a conversion rate to thoracotomy of 12% to 25% due to the inability to identify nodules (13,14). Several groups have compared conventional VATS palpation with intraoperative lung ultrasound (ILU) for nodule localization. The reported nodule identification success rate with palpation ranged from 47% to 97% (15-20). At the lower end of this spectrum, the reliance on palpation reflects poor sensitivity, which represents its most significant limitation. Additionally, digital nodule palpation often necessitates larger incisions, potentially leading to increased postoperative pain and recovery time (21,22).

Percutaneous CT-guided device placement

Percutaneous CT-guided device placement is one of the most commonly use techniques for intraoperative identification of pulmonary nodules. Success rates using these techniques for nodule localization are well studied and reported in the literature ranging from 93% to 100% (23-32), making percutaneous CT-guided device placement an effective technique. The success is likely related to the availability across centers and reproducibility (33). However, this procedure has several limitations and disadvantages. First, the percutaneous approach places patients at risk of post-procedural complications, including pneumothorax (10–47%) (24-26,28-30,34), pneumorrhagia (6–35%) (24-26,28-30,34) and hemoptysis (0–2%) (24,28). The most concerning but rare complication is air embolism, described as fatal in some cases (35,36). Concomitantly, this procedure requires the coordination of interventional radiologists and surgeons’ schedules, along with the associated departmental resources. Devices are at risk of dislodgement both during placement, since the patient is usually awake, and while the patient is on the way to the operating theater (23,25,26,36). Lastly, this technique is not amenable to all pulmonary nodules. For lesions in proximity to major structures (heart, large blood vessels or nerves) and located in certain anatomical regions (diaphragmatic angle, anterior to scapula), percutaneous device placement should be avoided given the risk of injury to surrounding structures or lack of a clear tract (37).

The two main devices currently used are the hook-wire and microcoil, with the hook-wire being the most often used technique (23). The hook-wire technique is simple, performed in a short period of time and is used by other surgical specialties, enabling the transfer of knowledge and equipment between specialties. For example, Yan et al. (26) performed a retrospective study of 74 patients using a recent system developed for localization of breast nodules, with a success rate of 93.2%, an average depth of 1.7 cm and a 6.8% rate of dislodgement. To reduce the risk of dislodgement, the use of the four-hook needle is gaining interest, which uses a metal four-hook anchoring to the pulmonary parenchyma and leaving a marker wire in the visceral pleura instead of the classic metal wire (23). In comparison, the microcoil has a lower reported rate of dislodgement than hook-wire (23,25). In the classic method described (38), the interventional radiologist leaves only the head of the microcoil in the proximity or within the nodule. The identification of the head then requires intraoperative fluoroscopy, a likely reason why hook-wire is still favored. The tailing approach is a new approach, which leaves the tail of the microcoil outside the visceral pleura and in the pleural space, which enables direct intraoperative visualization of the microcoil without fluoroscopy (23-25,32). In a recent comparative study, Sun et al. (25) compared classic hook-wire to the trailing microcoil approach. The localization success rate for microcoil was reported at 99%, with only 1 case where the tail was too short for identification. This rate was significantly higher compared to the 93% hook-wire group success rate. The microcoil was also associated with a significant decreased incidence of pneumorrhagia and depth of needle penetration, correlating that deeper penetration into the lung parenchyma is associated with more vascular injuries. Furthermore, multivariate analysis suggested that with hook-wire localization, shorter depth of needle penetration into lung tissue and longer duration between localization to VATS, were risk factors for dislodgement of localization device (25).

Multiple attempts have also been made to decrease the device dislodgement rates and extend the interval between device placement and resection to its limit. The limitation of the hook-wire technique is the weak tissue attachment in the shallow lung parenchyma, especially in the first 1 cm of penetration (25). Patients are therefore instructed to limit movements, even in the event of pain secondary to the wire implantation, and it is recommended that the resection be performed on the same day, since the wire is externalized. Microcoil insertion is not associated with movement restrictions. Huang et al. (24) published a retrospective analysis of microcoil placement using the tailing approach, with tails of 2–3 cm outside the visceral pleura. The dislodgement rate did not significantly vary between patients who underwent VATS resection on the same day, the following day or more than two days after microcoil insertion. Most patients did not report obvious symptoms or discomfort after microcoil insertion. With comparable complication rates reported in the literature, their results showed the safety and efficacy of microcoil localization and VATS resection on different days. The great advantage here is allowing flexibility in the device placement and resection schedules.

Other device placement techniques include fiducial marking which would be the third most reported technique. Gold (39) and I-125 (40,41) seeds are examples of material used in fiducial marking. The accuracy rate of gold fiducial marking was reported to be 98% by Sancheti et al. (39). Most of their patients underwent marking and surgery on the same day with a 9% post-procedural complication rate. Fra-Fernandez et al. (40) published a series describing 34 nodules localized with I-125 seeds, with a success rate of 88% and high complication rate with 31 complications reported. This series distinguished itself with 69% of the patients undergoing surgery several days after localization, with a series mean of 7.7 days (range, 3 to 16 days).

Altogether, percutaneous CT-guided device placement for pulmonary nodule localization is widely available and has a high reported success rate. However, the complication profile is the main disadvantage. The microcoil technique is associated, in the more recent literature, with lower complication and dislodgement rates (25,30), making it a superior device localization technique. Microcoils are used in other clinical contexts (e.g., angioembolization) with good tissue compatibility. Combined with its soft structure, microcoils do not cause significant damage to lung parenchyma and could explain the lower vascular complication rate. The pneumothorax rate is similar or lower between microcoil and hook-wire (24-26,30,31), giving the superiority to microcoil in this category as well. The possibility of extending the localization procedure and operation to multiple days is associated with less reported discomfort making the microcoil technique more patient friendly. Overall, the microcoil showed a superiority in device choice during our recent literature review. However, the new microcoil tailing technique requires more expertise and is technically more challenging for interventional radiologists. Furthermore, cost may be prohibitive as some studies report higher costs associated with the microcoil localization technique (25).

Percutaneous CT-guided agent injection

Another form of percutaneous lung parenchymal marking is with agent injections. Several different dyes have been reported in the literature for this technique. A non-exhaustive list includes methylene blue (36), lipiodol (42), indocyanine green (ICG) (43-45) and Technetium 99 (46,47). The technical aspects of percutaneous dye injection for nodule localization are similar to device placement. Strengths and weakness of these approaches therefore overlap. The success rate reported in the literature for nodule marking is between 91% to 100% (36,42-45,47,48) when all dyes are combined. When looking at accuracy in intraoperative marking (i.e. dye correctly identify and enable parenchymal resection that includes the nodule), Gkikas et al. (48), as an example, reported an estimate 97.3% accuracy of the ICG in their systematic review.

Dye injection offers the benefit of low cost and broad availability, as most dyes are already in use across various medical specialties. In terms of post-procedural complications, dyes have a similar profile to other percutaneous approaches with an overall complication rate ranges between 0% to 46% (36,42-45). In individual comparative studies, complication rates in single center were found similar (36) or inferior (45) when compared to percutaneous device placement. However, less major complications, such as air embolism or unstable pneumothorax, are reported. This may suggest that dye injection has a better safety profile than the use of solid devices.

Several weaknesses have been identified in studies specific to dye injection. The first concern is dye diffusion between injection to visualization via VATS or RATS (43,49). Different techniques are currently used to minimize dye diffusion, aside from reducing the time between injection and resection. For example, ICG is often mixed with iopamidol (44) or albumin (50) for this reason. In addition to diffusion, the dye can also impact the surrounding tissue, disrupt the tissue integrity and impact of histopathologic interpretation of the resected specimen.

As previously noted, percutaneous dyes tend to have a better safety profile with very similar success and accuracy rates, compared to percutaneous device placement. In a retrospective cohort study, Kleedehn et al. (36) compared hook-wire placement to methylene blue injection. Localization was successful at 100% in the dye injection group compared to a 96% success rate with hook-wire localization, which had an additional 13% dislodgement rate. While overall complication rates were similar, reported at 46% in the dye injection group versus 54% in the hook-wire group, the types of complications differed. The dye group experienced a significantly higher incidence of post-procedural cough, which the authors attributed to pleural irritation from the dye. Rates of pneumothorax and pneumorrhagia were similar between groups. Importantly, the study reported no issues with dye diffusion in the context of same-day surgery.

Systemic injection

The main agent used for systemic injection in identification of lung nodule reported in literature is ICG. The identification of pulmonary nodules with ICG relies on the enhanced permeability and retention effect. This effect occurs secondary to the high permeability of blood vessels and neoangiogenesis observed in tumors. The ICG therefore accumulates preferably in tumors and poor lymphatic washout promotes the retention in the tumor environment (48,51). This propriety is very useful for patients with multiple synchronous lesions, where the systemic ICG would preferably accumulate in all concerning lesions (51,52). Unfortunately, ICG also accumulated in areas of inflammation, making it a less specific (53). ICG is widely used in a number of different specialties and is easily accessible. Simultaneously, the reported complication profiles showed minimal complication rate (48,52,53) at doses as high as 5 mg/kg (53).

Gkikas et al. (48) published a meta-analysis of ICG use in lung nodule localization, The meta-analysis included 30 studies accounting for 1,776 patients when combining all three approaches. From those, 8 studies focused on systemic injection of ICG. The vast majority (87.5%) used the same administration dose at 5 mg/kg, with intervals between injection and resection ranging from 12 to 96 h. No complications were reported. The reported accuracy of systemic ICG injection at identifying pulmonary tumors was 83.5%, with a sensitivity estimated at 88% and specificity at 25%. All studies included used ICG for localization of nodules within 2 cm of the visceral pleura.

A more targeted agent under investigation for lung cancer is OTL38, a folate analogue conjugated to the near-infrared (NIR) dye S0456 (54). While currently Food and Drug Administration (FDA)-approved for use in ovarian cancer, OTL38 is being studied for its potential in pulmonary malignancies. It targets the folate receptor alpha, which is expressed in approximately 90% of pulmonary adenocarcinomas and 70% of squamous cell carcinomas (54,55) at levels up to 105 fold higher than in surrounding lung parenchyma (55). The agent is injected 3 to 6 hours prior to the resection and requires a specialized thoracoscope for intraoperative visualization.

In an early series published by Predina et al. (54), OTL38 enabled the intraoperative identification of 16 out of 21 targeted GGOs, and 20 out of 21 nodules were successfully detected on the back table with no adverse events reported. In terms of complication pattern, a phase II clinical trial of 100 patients reported 12 patients with grade I reaction, 6 with grade II reaction, and 2 with grade III events (56), with the main adverse event observed being nausea. To date, all studies using OTL38 identified nodules at a distance from the visceral pleura ranging from 0.0 to 2.7 cm, slightly above the maximum 1.5–2.0 cm classically reported with the ICG (53,57).

The use of systemic agents that preferentially accumulate in tumor or targeted lesions gives two main advantages. First, margins can be assessed in the specimen directly on the back table (54,55). Second, this enables the specific detection of new nodules, potentially not identified on imaging, leading to the resection for diagnosis and/or treatment. In a cohort of 100 patients, Gangadharan et al. (56) found nine additional cancerous nodules using OTL38. Systemic marker use does not necessitate a steep learning curve. In the same study, Gangadharan et al. (56) reported an average use of 15 minutes of fluorescence and that surgeons were comfortable with the image quality by 10 cases. With minimal adverse events and complications reported in the above studies, systemic injection of markers are a very promising avenue for pulmonary nodule marking.

Electromagnetic navigation bronchoscopy (ENB)

ENB was first described as a lung nodule biopsy technique (58,59). Modification of the original technique enabled interventional respirologists and thoracic surgeons to perform transbronchial dye injection as a technique for pulmonary nodule localization. The described technique is homogenous across the literature (33,58,60-62). A potential new avenue for the ENB technique could be the use of solid marking devices in contrast to the vastly used dyes. Multiple small studies have reported the use of ENB for placement of fiducial in cases of stereotactic radiosurgery, using fiducial as markers (63-65). Only one example of an alternative to dye marking via ENB was found for pulmonary lung nodule localization. Cheng et al. (66) described a dual technique of nodule marking, via ENB, using at the same time ICG and microcoil localization. The authors reported only 1 dislodgement from 15 patients (7%) and 100% resection rate of the targeted nodule.

Across the literature, ENB localization success with intraoperative visualization of the dye ranges from 88% to 100% (33,58,60-62,67,68). The first major strength of ENB is the complication rate. The main complication reported is bronchial bleeding, almost unanimously minor, at 0% to 6% (33,58,60-62,67). Therefore, ENB is low risk, with most studies reporting no complication related to the localization procedure. Furthermore, the endoscopic approach allows the localization of multiple and even bilateral nodules. Jeong et al. (67) published a series focusing on patients with 2 or more nodules. Localization was done on multiple ipsilateral lobes in all patients, with 94.4% of nodule amenable to ENB localization and an accuracy of marking at 88.2%. All nodules were resected and notably no VATS cases were converted to a thoracotomy. The reduction of the global procedural time is another strength of the ENB. Bolton et al. (60) were among the first to describe a significant reduction in total procedural time, mainly reducing the time between the end of procedural localization and start of surgery. This is achieved by combining the endoscopic and VATS in the same procedure, using the same operating theatre (avoiding patient travel) and general anesthesia. The use of general anesthesia for localization procedures thus also avoids patient discomfort.

On the other hand, ENB has disadvantages. Multiple authors reported a steep learning curve and expertise required to implement this technique in a new center (58,60,61). ENB necessitates a new skill set from interventional respirologists and surgeons, as well as expertise from radiologist, which make it less available across centers. Longer OR times are also required, given that both localization and resection are performed under the same anesthetic. Combined with the equipment required for ENB and the intraoperative visualization equipment for the specific dye used, this technique has a potential low cost-effectiveness (61). Regarding nodule localization, ENB does have limitations when targeting superficial lesions, especially in the absence of a bronchus sign on imaging. Some authors place the localizing agent in the surrounding area from the nearest bronchus (50,67), thus losing theorical accuracy.

Comparisons have been made between the ENB and percutaneous approach for dye injection localization. Yang et al. (61) published a comparative series of ENB and percutaneous CT-guided injection of ICG. ENB required double marking in more cases (3 compared to 0), but no complications were reported in the ENB group, compared to 5 pneumothoraxes in the CT-guided group. The authors did appreciate that the bronchoscopic approach facilitates access to nodules not accessible via percutaneous approach (i.e., near costophrenic angle, behind scapula). Gkikas et al. (48) reported similar success rate for percutaneous CT-guided and ENB injection of ICG, at 94.4% and 95.4% respectively. Intraoperative accuracy was similar with 97.3% and 95.5% respectively again.

ILU

ILU represents an alternative to the above-mentioned methods requiring external agents. Intraoperative ultrasound has a growing role in management of multiple cancers, including intrabdominal tumors. Ultrasound relies on tissue echogenicity to identify lesions and has been proven to successfully differentiate pure GGOs to solid pulmonary nodules. For example, Kondo et al. (69) correctly identified 100% of 53 GGOs measuring less than 20 mm by confirmation with back table examination of pulmonary wedge specimens. Overall, the success rate of ILU nodule identification reported in the literature is between 93–100% (15-19,70).

The use of ILU presents multiple advantages. Unanimously, no complication related to the use of ILU has been reported (15,16,70,71). The only theorical risk stated is the tissue manipulation and possible trauma to the visceral pleura, however, this is not the case practically. ILU also allows the identification of new lesions, not identified on imaging studies. The use of ILU is also shown to be time efficient. Gambardella et al. (15) demonstrated a significant reduction in the time to identify nodules when combining VATS with IUL compared to VATS palpation techniques (7.1±2.2 vs. 13.8±4.6 minutes respectively, P<0.05). Similar findings were observed by Hou et al. (16), where it took 7.09±1.80 minutes to localize a nodule with the use of ultrasound with VATS compared to 9.67±2.62 minutes with palpation (P<0.05). ILU also enables the surgeon to mark targeted resection margins during the procedure and assess specimen margins on the back table to confirm adequate excision; this supports optimal oncologic resection. A final key advantage of ILU is its on-demand availability, which sets it apart from other commonly used localization techniques that require preoperative coordination. ILU probes, typically 10 mm in diameter, are compatible with standard VATS and RATS (72) ports, allowing seamless integration into minimally invasive procedures. Mattioli et al. (17) aptly stated: “You use it when you need it,” highlighting the flexibility that ILU offers over more logistically complex alternatives.

Despite its favorable safety profile and high accuracy, ILU has notable limitations. Ultrasound is a highly operator-dependent modality that requires substantial training and experience. In reviewed studies, most of the operators had significant experience with intraoperative ultrasound and performed surgery in specialised centers (15). Moreover, ILU is not suitable for all patients. Effective sonographic imaging typically requires complete lung deflation, which can be difficult, or even impossible, to achieve in patients with asthma, chronic obstructive pulmonary disease, or significant pleural adhesions. These conditions are common among patients encountered in thoracic surgery clinics and operating rooms. In the series by Kondo et al. (69), they were able to identify 100% of the GGOs, even if 57% (30/53) of the patients did not have complete lung collapse. This highlights that this is an operator-dependant technique. Techniques to achieve complete lung deflation that may be useful to enhance the utility of ILU have been described including CO₂ insufflation (16) or slow pressure on the parenchyma with bronchus washout (69). Overall, ILU represents a promising approach for pulmonary nodule localization but remains limited by accessibility and a lack of large-scale evidence. To address this gap, larger trials are currently underway (73).

Emerging methods

Radiofrequency

Radiofrequency indentification (RFID) for lung nodule localization utilizes near-field radio communication technology to detect markers placed bronchoscopically prior to surgery. Miyahara et al. (74) recently demonstrated the technique’s safety, reporting no associated complications, as well as its efficiency, highlighting its rapid deployment in the operative setting. Additional potential advantages of RFID include real-time intraoperative feedback on marker location, improved accuracy for deeply located or small nodules, and the ability to integrate with minimally invasive approaches such as VATS or RATS. Limitations include the need for specialized equipment, operator training, and potential difficulty in detecting markers in dense or emphysematous lung tissue, which may affect signal transmission. Further multicenter studies are needed to evaluate long-term outcomes, reproducibility, and cost-effectiveness of this approach.

Three-dimensional (3D) reconstruction

3D reconstruction technology is used in some centers to assist with surgical planning and guidance for nodule resection. This technology represents an assistance more than a proper marking technique (37,75,76). Nevertheless, Natale et al. (37) did show a significant decrease in resection time when 3D reconstruction was combined with palpation compared to an approach without reconstruction. Beyond operative efficiency, 3D reconstruction may enhance preoperative planning by allowing surgeons to visualize complex nodule locations relative to bronchi, vessels, and fissures, potentially improving margin clearance and reducing intraoperative uncertainty. Limitations include the need for high-quality preoperative imaging, time and expertise for image processing, and cost or availability of software in some centers. Integration with other localization methods, such as RFID or dye marking, may further optimize outcomes.

Experimental probes

Other techniques reported in the literature involve experimental probes. For example, Barmin et al. (77) developed an endoscopic probe capable of recording tissue density and were able to achieve a detection rate of 81%. Similarly, other studies have explored the use of probes designed to measure the bioimpedance spectrum of lung tissue, though these have so far only been tested in small in vitro groups (78-80). None of these new probes have emerged on the market yet.

Magnetic Occult Lesion Localization Instrument (MOLLI) magnetic localization

A final example is our team’s proposal to explore the use of the MOLLI Magnetic Localization system, which was originally developed in Toronto for breast tumor localization. To date, there are no published reports on the application in thoracic surgery, but a similar system was previously described. The M-GOLL (Magnetic-Guided Occult Lesion Localization) was described in a case series with great success (81). Compared to the M-GOLL, the MOLLI system offers the same wire-free and radiation-free approach, using a percutaneously placed magnetic marker. Intraoperatively, a handheld wand detects the marker and provides real-time distance and depth measurements to guide resection. The advantages of the MOLLI are having no restriction on metal instruments, electrocautery use and a smaller marker. The application for pulmonary nodule identification seems plausible and is already approved by Health Canada and the FDA for example. While further research is needed to assess its efficacy and safety in thoracic applications, this technology holds promise as a novel localization method.

Hybrid operating rooms (HORs) and image-guided video-assisted thoracoscopic surgery

HORs are increasingly available and represent an important advancement in pulmonary nodule localization; no comprehensive review would be complete without their inclusion. Growing interest in thoracic surgery has expanded their use in this field. HORs support the concept of image-guided video-assisted thoracoscopic surgery (iVATS), first described by Gill et al. (21). This single-stage approach enables both localization and resection of small pulmonary nodules during the same procedure, using intraoperative percutaneous CT guidance under a single anesthetic. Compared to the traditional staged approach, HORs offer potential advantages, including the elimination of patient transfer between departments, reduced risk of marker dislodgement, and immediate management of complications (81). Reported success rates for marker-guided VATS resections performed in HORs range from 87% to 100%, with postoperative complication rates comparable to those of standard VATS procedures (21,29,34,82-84). This high success rate is likely attributable to the ability to use real-time imaging (both fluoroscopy and CT) to accurately localize markers, confirm their position relative to the stapler, and verify complete excision within the specimen. In a review by Melloni et al. (82), no single localization technique received a definitive recommendation, reinforcing that a range of options, remain viable based on local expertise and available resources.

Despite their advantages, HORs present several system-level limitations. As HORs are shared among various surgical specialties, routine availability for thoracic procedures may be constrained. Given that VATS resection of pulmonary nodules or masses is among the most frequently performed operations by thoracic surgeons (as reported by the Society of Thoracic Surgeons) the implementation of iVATS is unlikely to be feasible in institutions lacking either a dedicated thoracic operating room or exclusive shared access with a complementary service.

From an equipment standpoint, not all angiography tables are compatible with the lateral decubitus position commonly required for thoracic surgery. Alternatives such as dome-like gel positioners may be necessary to achieve optimal positioning (82). Furthermore, successful integration of iVATS requires not only surgical expertise but also proficiency across the entire operating team, including anesthesia, nursing, and radiology staff. The learning curve is nontrivial; for instance, Hsieh et al. (83) reported a 40% collision rate between the imaging system and the patient in their initial cases, often resulting in breaks in sterility. However, collision rates significantly decreased after the first 30 cases, alongside reductions in operative time and patient radiation exposure between the first and second halves of their early experience.

Several studies have compared single-stage iVATS procedures performed in HORs with the traditional two-stage approach involving preoperative localization in a CT suite. Chen et al. (29) reported a 92% localization and resection success rate in the HOR group versus 100% in the CT-room group. Although localization time was longer in the HOR setting, the overall procedure time was shorter. Radiation exposure, however, was significantly higher in the HOR group.

Similarly, Chao et al. (34) found comparable localization success rates between HOR (91%) and conventional CT-room (93%) groups. Localization times were similar across both modalities, and while the incidence of pneumothorax was higher in the CT-room group, no cases required intervention. Postoperative outcomes and hospital length of stay were equivalent between groups.

Discussion

Summary and implementation considerations

Table 2 summarizes the key features of the localization techniques discussed in this review. Notably, all reported methods demonstrate high success and accuracy rates for pulmonary nodule marking. Simultaneously, there is growing interest in synchronizing nodule localization and resection, particularly through single anesthetic events (SAEs) (86,87). SAEs are increasingly favored in thoracic surgery, where both diagnosis and treatment can occur on the same day. As of now, all techniques discussed are potentially adaptable to this single-stage workflow. Differentiation among them depends on their individual strengths and limitations, particularly in relation to their anatomical approach and feasibility of integration.

To guide institutions in selecting an appropriate technique, we present two perspectives. First, we assess feasibility of implementation based on reports from the literature. Techniques were categorized into three tiers of complexity, as shown in Figure 1 and reported in Table 2.

Figure 1 Classification of localization techniques by feasibility of implementation, divided into three categories based on the level of resources and institutional support required. See Discussion for details. 3D, three-dimensional; ICG, indocyanine green; MOLLI, Magnetic Occult Lesion Localization Instrument; OR, operating room.

Category 1: surgeon-level implementation

These techniques can be adopted by an individual or small group within a service without major infrastructure changes. This includes most percutaneous approaches, which rely on equipment already common in most hospitals, minimizing cost required for acquisition. For example, hook-wire localization is routinely used in breast cancer surgery (26), microcoils in angioembolization (27), and fiducials (e.g., I-125 seeds) in prostate cancer (40). Similarly, ICG, a cost-effective and widely available dye, is already used in specialties such as hepatobiliary surgery (48,51,57). The MOLLI magnetic localization system, though not yet validated for pulmonary applications, also fits into this category based on its portability and minimal infrastructure requirements.

Category 2: service-level implementation

These techniques require more advanced expertise and investment in specialized equipment or software, necessitating support from the department or institution. Examples include ILU, ENB, and 3D reconstruction tools. Successful integration of these approaches often depends on coordinated efforts among surgeons, radiologists, and anesthesiologists, along with institutional support for acquiring and maintaining the necessary systems.

Category 3: institution-level implementation

HORs represent the most complex and resource-intensive technique. Although widely used in cardiac and vascular surgery, their availability is often limited, and scheduling conflicts can arise. Implementing iVATS for pulmonary nodule localization would require either significant restructuring of HOR usage or construction of a dedicated suite for thoracic surgery. This also includes training a multidisciplinary team to work efficiently in this environment. As such, while offering high precision and promising outcomes, HORs are the most challenging to implement in practice.

Given that many centers may have access to multiple technologies and differing levels of expertise, we propose a preliminary decision-making algorithm to help guide technique selection (Figure 2). Although nodule depth is often discussed in the literature (42,43,85), most techniques report efficacy for lesions located up to 5 cm from the pleural surface (see Table 2). Therefore, our algorithm focuses on anatomical considerations rather than depth alone. The first decision point divides nodules into those located in the outer third versus inner third of the lung parenchyma. This follows the classification used in percutaneous studies, where peripheral lesions are more amenable to percutaneous and ultrasound-guided approaches. In contrast, deeper nodules may be better suited to ENB or systemic dyes. Gkikas et al. (48) previously noted this tendency in their systematic review, with peripheral nodules favoring percutaneous methods and central lesions more often approached bronchoscopically. An additional anatomical consideration is proximity to major structures. Percutaneous access is contraindicated near the heart, great vessels, major nerves, or where the shortest access path is blocked (e.g., near the scapula or diaphragm). In such cases, probe-based or bronchoscopic approaches offer safer alternatives, especially when combined with real-time imaging. This algorithm depicted in Figure 2 represents an effort to organize the growing and diverse body of literature on pulmonary nodule localization.

Figure 2 Proposed decision-making algorithm to guide technique selection in centers where multiple localization options are available. The algorithm is based on anatomical characteristics of the pulmonary nodule and leverages the strengths of each technique. It is intended as a conceptual framework, not a clinical guideline. ICG, indocyanine green.

Limitations and future directions

This review summarizes literature identified by our team and is not intended as a systematic review. As such, limitations in methodology and completeness are acknowledged. We encourage readers to conduct additional searches and contribute further studies to strengthen the evidence base. Importantly, the proposed algorithm is not a clinical guideline, but rather a conceptual scaffold to facilitate institutional planning and stimulate future research. As more techniques are developed, the choice of localization method will become increasingly individualized to the patient and the clinical circumstances surrounding the procedure.

Most of the literature consists of case series or small- to medium-sized cohorts. Comparative studies evaluating more than two techniques are rare, making it difficult to establish clear, evidence-based guidelines. Moreover, diversity of available techniques contributes to a fragmented evidence base, limiting direct comparisons. In some cases, certain techniques lack recent literature, necessitating the inclusion of older studies. Publication bias is also likely, with many reports highlighting high success rates that may not reflect real-world outcomes, and comparative studies sometimes emphasizing the technique favored by the authors. Robust, multicenter comparative studies remain essential to validate effectiveness and inform best practices.

Important perspectives are also underrepresented in the current literature. Only a minority of studies include patient-reported outcomes, making it difficult to fully integrate the patient perspective into decision-making. Comfort, tolerance, and anesthetic considerations, particularly for patients who may benefit from less invasive techniques despite lower precision are seldom addressed in detail. Cost considerations are similarly limited; few studies provide robust cost analyses, and comparisons are challenging due to differences in institutional resources, equipment availability, and pricing among manufacturers. In addition, in some regions, CT-based lung cancer screening programs have not been adopted due to concerns about cost-effectiveness, especially given the high proportion of detected GGOs that are ultimately non-malignant.

Future studies should aim to incorporate patient-centered outcomes, standardized cost analyses, and region-specific considerations for screening program adoption. Such data would enhance decision-making, optimize resource allocation, and support equitable access to effective localization techniques worldwide.

Conclusions

Advancements in intraoperative localization techniques have significantly improved the precision of pulmonary nodule resection in minimally invasive thoracic surgery. While traditional approaches such as percutaneous device placement or dye injection remain widely used, emerging methods demonstrate high success rates with fewer complications. Each technique has distinct advantages and limitations, and optimal selection depends on institutional infrastructure, team expertise, patient-specific considerations, and importantly, regional factors such as cost-effectiveness and resource availability. Recognizing that some health systems have not adopted certain modalities due to these constraints, ongoing innovation, multicenter collaboration, and cost-effectiveness research will be key to refining localization strategies and expanding equitable access worldwide.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://vats.amegroups.com/article/view/10.21037/vats-25-23/rc

Peer Review File: Available at https://vats.amegroups.com/article/view/10.21037/vats-25-23/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://vats.amegroups.com/article/view/10.21037/vats-25-23/coif). A.W. received honoraria from AstraZeneca (AZ), Merck, and Bristol Myers Squibb (BMS) for lectures and participation in advisory boards. She also serves as a Board Member of LUNGNSPEI, a non-profit organization, and provides expert opinions to MedCounsel. The other 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.

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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