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Purpose The purpose of this study was to evaluate the feasibility and safety of transbronchial cryoablation with a novel flexible cryoprobe using nitrogen as the refrigerant in an in vivo porcine model of lung parenchyma. Materials and methods A novel flexible cryoprobe using nitrogen as the refrigerant was used for transbronchial cryoablation of lung parenchyma in six normal female pigs. The cryoprobe was delivered to the distal bronchus in the bilateral porcine lungs via the bronchoscopic working channel under virtual bronchoscopy guidance. The position was confirmed with real-time computed tomography (CT). The whole procedure included two freeze-thaw cycles (15 min and 2 min, respectively). CT images were obtained during cryoablation and at 24 h, one week, two weeks and four weeks after the treatment to assess the effectiveness and safety of the procedure. Ablation zone tissue samples were obtained at 24 h and four weeks after the cryoablation for further histopathological analysis. Results All ablation procedures (12/12; 100%) were performed successfully. No major complications occurred during the procedure or the observation period. The ablation zones were clearly depicted on CT with a maximal ablation zone volume at 24 h (21.88 ± 12.61 [SD] cm3) compared to 3.64 ± 2.06 (SD) cm3 and 10.73 ± 3.84 (SD) cm3 at the end of the 1st and 2nd freeze-thaw cycles, respectively (P Conclusion The novel flexible bronchoscopy-guided cryoablation is a feasible, safe and effective modality in an in vivo porcine model of peripheral normal lung parenchyma, suggesting potential capabilities for the treatment of peripheral lung cancer in humans.

Endobronchial intervention is increasingly used as a minimally invasive means for the treatment of pulmonary diseases. In order to acquire the position of bronchoscopy, vision-based localization approaches are clinically preferable but are sensitive to visual variations. The static nature of pre-operative planning makes mapping of intraoperative anatomical features challenging for learning-based methods using visual features alone. In this work, we propose a robust navigation framework based on Vision Kinematic Interaction (VKI) for monocular bronchoscopic videos. To address visual-imbalance between the virtual and real views of bronchoscopy images, a Visual Similarity Network (VSN) is proposed to extract domain-invariant features to represent the lumen structure from endoscopic views, as well as domain-specific features to characterize the surface texture and visual artefacts. To improve the robustness of online estimation of camera pose, we also introduce a Kinematic Refinement Network (KRN) that allows progressive refinement of camera pose estimation based on network prediction and robot control signals. The accuracy of camera localization is validated on phantom and porcine lung datasets from a robotically controlled endobronchial intervention system, with both quantitative and qualitative results demonstrating the performance of the techniques. Results show that the features extracted by the proposed method can preserve the structural information of small airways in the presence of large visual variations along with the much-improved camera localization accuracy. The absolute trajectory errors (ATE) on phantom data and porcine data are 8.01 mm and 8.62 mm respectively.

Background Accurate preoperative localization of small pulmonary nodules facilitates the rapid and precise video-assisted thoracoscopic surgery (VATS). This study aims to evaluate the feasibility, safety, and efficacy of navigation bronchoscopy-guided pulmonary microcoil placement for preoperative pulmonary nodule localization. Methods Twelve lung lesions were simulated by mixing lipiodol in three porcine models. After 1 week, two microcoils per lesion were deployed under bronchoscopic guidance. Computed tomography scans were then performed 1 day, 1 week, 2 weeks, and 4 weeks after the deployment to assess the position of the microcoils relative to the lesions. Surgical resection of the simulated lesions was performed under fluoroscopy 5 weeks after the deployment and the accuracy, stability, and associated complications of the microcoil localization were evaluated. Following this, an exploratory clinical study was conducted on three patients with pure ground-glass pulmonary nodules. Results The mean diameter of the twelve simulated lung lesions was 9.55±2.36 mm, and the mean distance from the pleura to the lesions was 8.29±2.99 mm. Twenty-four pulmonary microcoils were implanted in the bronchi surrounding the lesions. Four weeks later, the mean distance between the microcoils and the center of the lesions was 16.12±8.97 mm and the average migration of the microcoils relative to the baseline position (1 day after implantation) was 3.48±4.56 mm. All microcoils and target lesions were successfully resected in both the animal experiment and clinical study and no complications, such as pneumothorax, were observed during marker implantation or postoperative follow-up. Conclusions The preoperative localization of pulmonary nodules by navigation bronchoscopy-guided microcoil placement is a safe, stable, and effective technique with minimal complication risk. This procedure can assist subsequent thoracoscopic resection.

Primary tracheal leiomyoma is exceedingly rare and recommended management has not been defined yet. Surgical management has been considered to be the standard treatment historically. Bronchoscopic intervention may be an ideal alternative for patients who refuse or are not fit for surgery. We report the first bronchoscopic submucosal dissection using an innovative water-jet Hybrid Knife performed on a patient with recurrent primary tracheal leiomyoma.

Rationale: Ferroptosis, a newly identified form of regulated cell death, can be induced following the inhibition of cystine-glutamate antiporter system XC- because of the impaired uptake of cystine. However, the outcome following the accumulation of endogenous glutamate in lung adenocarcinoma (LUAD) has not yet been determined. Yes-associated protein (YAP) is sustained by the hexosamine biosynthesis pathway (HBP)-dependent O-linked beta-N-acetylglucosaminylation (O-GlcNAcylation), and glutamine-fructose-6-phosphate transaminase (GFPT1), the rate-limiting enzyme of the HBP, can be phosphorylated and inhibited by adenylyl cyclase (ADCY)-mediated activation of protein kinase A (PKA). However, whether accumulated endogenous glutamate determines ferroptosis sensitivity by influencing the ADCY/PKA/HBP/YAP axis in LUAD cells is not understood. Methods: Cell viability, cell death and the generation of lipid reactive oxygen species (ROS) and malondialdehyde (MDA) were measured to evaluate the responses to the induction of ferroptosis following the inhibition of system XC-. Tandem mass tags (TMTs) were employed to explore potential factors critical for the ferroptosis sensitivity of LUAD cells. Immunoblotting (IB) and quantitative RT-PCR (qPCR) were used to analyze protein and mRNA expression. Co-immunoprecipitation (co-IP) assays were performed to identify protein-protein interactions and posttranslational modifications. Metabolite levels were measured using the appropriate kits. Transcriptional regulation was evaluated using a luciferase reporter assay, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA). Drug administration and limiting dilution cell transplantation were performed with cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. The associations among clinical outcome, drug efficacy and ADCY10 expression were determined based on data from patients who underwent curative surgery and evaluated with patient-derived primary LUAD cells and tissues. Results: The accumulation of endogenous glutamate following system XC- inhibition has been shown to determine ferroptosis sensitivity by suppressing YAP in LUAD cells. YAP O-GlcNAcylation and expression cannot be sustained in LUAD cells upon impairment of GFPT1. Thus, Hippo pathway-like phosphorylation and ubiquitination of YAP are enhanced. ADCY10 acts as a key downstream target and diversifies the effects of glutamate on the PKA-dependent suppression of GFPT1. We also discovered that the protumorigenic and proferroptotic effects of ADCY10 are mediated separately. Advanced-stage LUADs with high ADCY10 expression are sensitive to ferroptosis. Moreover, LUAD cells with acquired therapy resistance are also prone to higher ADCY10 expression and are more likely to respond to ferroptosis. Finally, a varying degree of secondary labile iron increase is caused by the failure to sustain YAP-stimulated transcriptional compensation for ferritin at later stages further explains why ferroptosis sensitivity varies among LUAD cells. Conclusions: Endogenous glutamate is critical for ferroptosis sensitivity following the inhibition of system XC- in LUAD cells, and ferroptosis-based treatment is a good choice for LUAD patients with later-stage and/or therapy-resistant tumors.