CT-guided Preoperative Localization of Pulmonary Nodules Using a Glucose Test and Tissue Adhesive

Summary

This CT-guided protocol localizes ground-glass nodules preoperatively using tissue adhesive and a glucose test, which verifies needle placement and prevents airway injection-enhancing safety and distinguishing it from prior localization techniques.

Abstract

Intraoperative localization of ground-glass nodules (GGNs) is challenging. This study evaluates a CT-guided protocol that innovatively combines a glucose solution test with tissue adhesive marking to enhance safety and efficacy. The standardized procedure involves preoperative thin-slice CT (≤1 mm) with a 5 × 5 cm grid for planning, followed by percutaneous puncture to a shallow (5 mm) subpleural depth. A key safety innovation is the injection of 0.3 mL of 5% glucose solution to confirm extra-bronchial needle position via cough reflex testing before depositing 0.3 mL of 2-octyl cyanoacrylate to create a palpable marker. This protocol not only achieves precise localization of pulmonary nodules but also significantly reduces the incidence of pneumothorax by minimizing the number of required puncture attempts. The method is readily reproducible and integrates seamlessly into standard preoperative workflows. This approach establishes a safer, non-radioactive alternative for GGN localization, with its core innovations -- the glucose confirmation step and shallow subpleural injection -- serving as key mechanisms for complication prevention.

Introduction

Over the past two decades, advancements in computed tomography (CT) imaging have dramatically increased the detection rate of small pulmonary nodules, particularly ground-glass nodules (GGNs), which often measure less than 1 cm in diameter and exhibit indistinct borders on conventional chest radiography¹. Concurrently, the number of thoracic surgeries performed to resect these nodules has risen sharply, driven by clinical guidelines recommending surgical intervention for suspicious GGNs to rule out malignancy². However, a critical challenge persists: intraoperative identification of GGNs remains highly unreliable. Unlike solid tumors, GGNs lack sufficient tactile feedback and visual contrast from surrounding lung parenchyma, making manual palpation or direct visualization ineffective in up to 40% of cases³. This limitation often forces surgeons to either extend incisions for broader exploration or risk leaving residual disease, both of which compromise patient outcomes.

To address this, preoperative localization techniques have emerged as essential tools to guide precise resection. Traditional methods, such as hookwire placement, were once considered the gold standard but are plagued by significant drawbacks. Hookwire systems, for example, require percutaneous insertion of a sharp-tipped wire under CT guidance, which carries a 15-30% risk of pneumothorax-complications that often delay surgery or require additional intervention⁴. Fluorescent dye injection, though less invasive, relies on specialized equipment for detection and may diffuse beyond the target nodule, reducing its utility in deep lung lesions⁵. Electromagnetic navigation bronchoscopy (ENB), although offering real-time tracking, is limited by the complexity of bronchial anatomy and requires prolonged procedure times, making it unsuitable for urgent cases⁶. These limitations underscore the need for a simpler, safer, and more versatile localization method.

Against this backdrop, CT-guided tissue glue injection has gained traction as a promising alternative. Tissue glue, typically composed of 2-octyl cyanoacrylate, is a biocompatible polymer that rapidly hardens upon contact with tissue, forming a palpable nodule. Upon polymerization within the lung, the tissue adhesive becomes distinctly discernible from the surrounding pulmonary parenchyma on CT imaging⁷. This dual-modality approach -- combining tactile feedback from the hardened glue with radiographic guidance -- addresses the core limitations of existing techniques. Unlike hookwire systems, it eliminates the need for secondary marker removal, reducing surgical time and patient discomfort. Unlike fluorescent dyes, its mechanical stability ensures consistent localization, even in deep lung segments.

The rationale for this method extends beyond its technical feasibility. Studies have shown that GGNs often lie within 3 cm of the pleural surface, a depth at which CT-guided puncture remains highly accurate⁸. By injecting glue just beneath the pleura, operators can create a stable marker that resists displacement during breathing or surgical manipulation. Additionally, the use of non-ionic iodinated oil minimizes the risk of allergic reactions, a common concern with other contrast agents⁹. These features collectively position CT-guided glue injection as a practical solution for centers lacking access to advanced navigation systems or specialized equipment.

Yet, this method is not without limitations. Its efficacy depends on operator experience in CT-guided puncture, as misalignment can lead to glue deposition outside the target area. Moreover, its utility diminishes for nodules deeper than 3 cm from the pleura, where needle deflection increases the risk of off-target injection¹⁰. Despite these constraints, early clinical reports suggest it compares favorably to traditional methods, with preliminary data showing a 90% success rate in localizing GGNs and a pneumothorax rate of less than 5%¹¹.

In the broader context of thoracic surgery, this technique aligns with a growing trend toward minimally invasive, patient-centered care. By reducing reliance on invasive procedures and minimizing radiation exposure from repeated imaging, it supports value-based healthcare goals¹². As technology advances -- such as the integration of artificial intelligence for real-time trajectory planning -- its applicability is likely to expand, potentially transforming how GGNs are managed globally.

For clinicians considering this method, key factors to assess include nodule size (preferably ≥5 mm), proximity to the pleura (≤3 cm), and patient eligibility for CT-guided procedures (e.g., no active bleeding disorders). While not a universal solution, it offers a robust option for many patients, bridging the gap between traditional and cutting-edge localization techniques.

Protocol

NOTE: All procedures involving human participants were approved by the Institutional Review Board of Zhongshan Hospital, Fudan University (Approval No. B2025－222R), and written informed consent was obtained from all participants.

1. Preoperative preparation

1. Patient eligibility assessment
   1. Verify eligibility for video-assisted thoracoscopic surgery (VATS). Confirm INR <1.5 and platelet count >50,000/µL. Rule out active pulmonary infection. Assess ability to maintain position for ≥30 min. Obtain written informed consent.
      NOTE: A comprehensive eligibility assessment minimizes procedural risks. Ensure VATS can be performed within 3 days post localization. Position the patient comfortably to facilitate prolonged immobility during the procedure.
2. Equipment and material preparation
   1. Gather a CT scanner capable of 1.0 mm slice acquisition, a 5 × 5 cm biopsy grid, a 22 G Chiba needle (15 cm length), 5% glucose solution, α-cyanoacrylate medical adhesive, 2% lidocaine, disposable transparent dressing bowls, 1 mL/2 mL/10 mL syringes, iodophor antiseptic solution, sterile scissors, sterile drapes, and vascular clamps. Verify all items are present before starting.

2. Localization procedure

1. Patient positioning and CT scanning
   1. Position the patient for optimal operator access and tolerance. Select a supine or contralateral decubitus position for anterior or lateral nodules; choose a contralateral decubitus or prone position for posterior nodules. Acquire a baseline CT scan with standard (5 mm) and thin-section (1 mm) reconstructions. Use the biopsy grid and a surgical marker to identify and mark the optimal skin entry point and plan the needle trajectory and depth based on the scan.
      NOTE: Thin-section CT is essential for precise nodule targeting.
2. Prepuncture preparation
   1. Disinfect the operative field with iodophor, apply sterile drapes, and infiltrate local anesthesia (2% lidocaine) from the skin to the parietal pleura. Create a central perforation in a disposable dressing bowl using sterile vascular clamp. Invert and position the bowl over the operative site, then secure it to the drapes with a vascular clamp. Align the puncture needle through the bowl's perforation so that it lightly contacts the marked entry point.
      NOTE: This setup maintains a sterile field and needle stability.
3. Needle advancement under CT guidance
   1. Advance the 22 G Chiba needle along the planned trajectory; shift the entire secured system (drapes and bowl) to adjust the needle angle or direction. Perform intermittent CT scans covering ±2 cm from the target after each 1-2 cm advancement, and stop advancement at 5-10 mm from the pleural surface. If positioning is suboptimal, adjust within the lung without exiting the pleura. If pleural re-entry is needed, complete it swiftly to reduce pneumothorax risk.
      NOTE: Incremental advancement with limited CT verification enhances accuracy while reducing radiation exposure. Avoiding pleural re-passage mitigates pneumothorax.
4. Needle tip verification using glucose solution
   1. Inject 0.3 mL of 5% glucose solution slowly at 0.05 mL/s. Monitor for immediate or intensifying cough; if coughing occurs, perform a limited CT scan. Withdraw the needle approximately 2 cm, reposition, and repeat the glucose test. If coughing persists, withdraw to the subcutaneous tissue and restart from Step 2.2.
      NOTE: Repositioning prevents adhesive from being injected into the airways. Glucose testing also flushes blood from the needle lumen, preventing premature adhesive coagulation.
5. Tissue adhesive marker deployment
   1. Inject 0.3-0.5 mL of α-cyanoacrylate medical adhesive. Allow 3 s for initial polymerization; then, withdraw the needle. Immediately assess for pain, headache, or cough.
      NOTE: Promptly evaluate for complications: headache may indicate air embolism (manage with Trendelenburg positioning and oxygen); escalating pleuritic pain suggests pleural leakage (treat with dexamethasone 10 mg and morphine 10 mg).
6. Marker position confirmation and complication assessment
   1. Perform a confirmatory CT scan immediately post injection. Verify a spherical or flake-shaped hyperdense marker adjacent to the nodule. Check for pneumothorax; if present, rescan after 5 min to assess progression. Perform tube thoracostomy if pneumothorax is significant or enlarging.
      NOTE: This scan confirms successful localization and guides the management of complications.

3. Postprocedure protocol

1. Complication monitoring and safety measures
   1. Perform an immediate postprocedural CT scan to evaluate for pneumothorax or hemorrhage. Handle the adhesive cautiously to avoid skin contact or vapor inhalation. Wear gloves and appropriate personal protective equipment. Dispose of sharps and biohazardous materials according to institutional protocols.
      NOTE: Vigilant monitoring and adherence to safety protocols are critical.
2. Patient transfer for surgery
   1. Transfer the patient to the preoperative holding area. Schedule VATS resection within 3 days of successful localization.
      NOTE: Timely surgery ensures the marker remains palpable intraoperatively.

Results

The aforementioned procedure involved the localization of a peripherally located lesion by targeting its medial aspect (Figure 1 and Figure2). A stepwise puncture technique was employed to access the target position. Following the injection of medical adhesive, the patient exhibited only mild coughing without other subjective complaints. Postoperative CT imaging revealed no significant pneumothorax or pleural effusion.

The procedu...

Discussion

The development of this CT-guided pulmonary nodule localization technique, which incorporates a glucose verification step and tissue adhesive injection, holds significant promise for advancing minimally invasive thoracic surgery. The glucose verification test is a critical procedural step that prevents inadvertent injection into the airway and thereby improves patient safety. With the increasing volume of pulmonary nodule resections, this method provides a reliable solution for identifying small, non-palpable lesions. Co...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Reagents & Consumables
Item			Specification / Notes
2% Lidocaine			Local anesthetic, sterile
5% Glucose Solution			For bronchial position testing
α-Cyanoacrylate Medical Adhesive			e.g., Dermabond; sterile, fast-curing adhesive
Biohazard Waste Container			For sharps and contaminated materials
Gauze, Sterile			For post-injection site care
Gloves, Sterile			Personal protective equipment
Iodophor Antiseptic Solution			e.g., Betadine for skin disinfection
Syringes			1 mL, 2 mL, and 10 mL sterile
Equipment & Instruments
Item			Specification / Notes
22G Chiba Needle			15 cm length, for percutaneous access
5 × 5 cm Biopsy Localization Grid			For CT-guided skin marking
CT Scanner			Thin-slice ≤1 mm capability
Dressing Bowl, Disposable			Transparent, for sterile needle guidance
Scissors, Sterile			For perforating dressing bowl
Surgical Marker Pen			For marking skin entry site
Vascular Clamps			To secure dressing bowl to drapes
Patient Support & Monitoring
Item			Specification / Notes
Chest Tube Kit			e.g., 14F, for pneumothorax management
Oxygen Supply			For management of symptomatic pneumothorax
Spirometry Device (optional)			For guided breath-hold if used
Software / Imaging Tools
Item			Specification / Notes
CT Workstation Software			For scan planning and guidance