Researchers identify novel diagnostic method to detect small lung nodules

Researchers from China have successfully utilized a mixture of tissue adhesive and iohexol to localize small and impalpable pulmonary lesions and nodules under CT guidance—a novel approach highlighted in a clinical study published in Thoracic Cancer.

“Small pulmonary nodule detection during video-assisted thoracoscopic surgery (VATS) or thoracotomy is frequently challenging; however, accurate and efficient localization of nodules is critical for precise resection,” the authors wrote. “[W]e introduce and evaluate the feasibility and safety of a novel technique for preoperative pulmonary nodule localization.”

The researchers identified 140 patients, with a total of 153 pulmonary nodules measuring less than 2 cm in diameter, for the study. They injected the mixture of tissue adhesive and iohexol to localize each nodule via preoperative CT guidance. They assessed patient/nodule characteristics, surgical data, localization data, complications, and pathological results.

Using the novel technique, the team identified all nodules preoperatively, with a mean nodule size of 8.7 ± 2.6 mm and a mean distance from nodule to pleura of 7.9 ± 8.2 mm. It took an average of 8.7 ± 1.0 minutes to visualize the nodules. In total, 6.4% of patients underwent two simultaneous nodule localizations and 1.4% underwent three simultaneous nodule localizations. Major complications included pneumothorax in 12.1% of patients, pain in 4.3% of patients, and malodor in 3.6% of patients. Notably, neither embolism nor allergic reactions occurred.

The wide dissemination of low-dose CT to screen for lung cancer has resulted in an explosion in the detection of indeterminate, small pulmonary nodules (SPNs). Although CT can provide detailed features of the lesions, patients are often referred to a thoracic surgeon for surgical resection.

VATS is considered the gold standard to diagnose and treat pulmonary SPNs, according to the authors. Unlike open-thoracotomy procedures, the minimally invasive nature of VATS is advantageous in decreasing postoperative pain and recovery time, as well as enhancing aesthetics. Importantly, VATS permits surgeons to biopsy, as well as definitively treat early-stage lung cancer. VATS is key in managing patients with peripheral and possibly malignant SPNs. On a related note, minimally invasive surgical methods such as the Da Vinci robotic surgery are common alternatives for biopsy and resection of pulmonary lesions.

“It is still challenging for surgeons to identify nodules by palpation or inspection during thoracotomy, especially when nodules are too small or lack sufficient consistency (eg, ground-glass opacities [GGOs]),” the authors wrote. “Using VATS for SPNs may also be challenging if the nodule is not easily accessible, or if it is located a certain distance from the pleural surface.”

Findings from previous research have indicated that lesions with nodule sizes <10–15 mm, and with a nodule-to-pleura distance of >10 mm, were undetectable on VATS. Ultimately, palpation of pulmonary nodules via a VATS access incision is challenging—particularly when the nodule is small and deep within the lung parenchyma, thus requiring preoperative localization.

Hook-wire placement, microcoils, and methylene blue injection have all been used in clinical practice to mark lesions preoperatively—these techniques require the percutaneous placement of localizing material (eg, hook-wire) or the injection of marking substances (eg, methylene blue). Although these approaches are satisfactory, they pose the risk of migration or spillage of the material utilized between the radiological intervention and surgery, ideally conducted rapidly and in sequence. Moreover, percutaneous nodule marking can lead to complications akin to image-guided lung biopsies, such as pneumothorax and bleeding, as well as air embolism. 

The current technique of using an injected mixture of tissue adhesive and iohexol as a localization marker demonstrated certain advantages, according to the authors. First, the adhesive is composed of monomeric n-butyl-2-cyanoacrylate, which polymerizes quickly when in contact with tissue fluid, thus forming a tough artificial nodule that is easily identified by inspection or palpation. Second, the adhesive is nontoxic.

Further, the tissue adhesive solidifies rapidly when in contact with tissue fluid, thus decreasing the risk of pneumothorax and embolism. Third, the iodine-contrast medium iohexol permits artificial nodules to be better-visualized on CT, and accentuates spatial relationships between the artificial and pulmonary nodule, thus allowing surgeons to optimize resection range during surgery.

“Our study demonstrates that this novel method is safe and straightforward to implement,” the authors concluded.