Citations

ABSTRACT Airway perforation is a potentially lethal complication from tracheal or mediastinal malignancies that require complex management. Advanced thyroid cancer is known to have high morbidity, and patients with tracheal metastatic lesions are vulnerable to injury. Therapeutic management typically comprises a combination of surgical and nonoperative treatment modalities, whose adverse effects can lead to significant airway injury. We present the case of a 67‐year‐old man with papillary thyroid carcinoma who developed a tracheocutaneous fistula following proton beam therapy and chemotherapy for metastatic disease. Airway repair and recanalization were successfully achieved through a combined surgical and bronchoscopic approach.

Abstract INTRODUCTION Guidelines recommend non-surgical biopsy for indeterminate pulmonary lesions > 8 mm. Shape-sensing robotic-assisted bronchoscopy (ssRAB) is growing in use to biopsy small pulmonary nodules; however current literature is limited to single center studies with limited follow-up. This study, PRECIsE, assessed safety and performance of the first ssRAB iteration across multiple sites and nascent users. METHODS Prospective, multicenter, observational study evaluating ssRAB without cone-beam CT guidance in patients with nodules 10–30 mm located in or beyond the sub-segmental airways. Patients were followed for 2 years; the primary endpoint was sensitivity for malignancy with diagnostic yield, and safety as secondary endpoints. Multilevel logistic regression models were used to control for factors associated with sensitivity and diagnostic yield. RESULTS A total of 305 procedures were performed across 6 centers. Median nodule size was 17.0 mm (IQR: 14.0–23.0) with bronchus sign present in 37% of cases. Sensitivity for malignancy through 2 years was 81.3% (95% CI: 75.7, 86.1). Multi-level modelling demonstrated female sex, smaller nodule size, lower lobe location, semi-solid density, and higher body-mass-index were associated with lower sensitivity. Diagnostic yield was 74.1% (95% CI: 68.8, 78.9) according to the ATS/ACCP criteria and 77.5% [95% CI: 72.4, 81.8] according to the intermediate criteria. Multi-level modeling demonstrated a non-significant site/center level effect on ATS/ACCP diagnostic yield (P = .36). Pneumothorax requiring intervention was 1.6% (5/305); bleeding was 1.0% (3/305) with two (2) Nashville grade 2 and one (1) Nashville grade 3 events. CONCLUSIONS The first iteration of ssRAB demonstrated encouraging performance and a strong safety profile among nascent users for the biopsy of small peripheral nodules.

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide, and despite advances in treatment, immune suppression remains an obstacle to effective therapy. Effector CD4+ T cells (CD4+ Teff) are critical for antitumor immunity, but their function is often inhibited by regulatory T cells (Treg), which accumulate in lung tumors and mediate suppressive functions through multiple mechanisms. This suppression leads to tumor progression and poor patient outcomes. However, the mechanisms underlying Treg-mediated suppression are not fully understood. Herein, we identify the extracellular adenosine 5-triphosphate receptor P2RX7 as a key regulator of Treg function in lung tumors. In a murine lung cancer model induced by Lewis lung carcinoma cells, we found that P2RX7 enhanced the suppressive capacity of tumor-infiltrating Tregs, promoting tumor growth. In T cell–specific P2RX7-knockout (P2RX7-KO) mice, reduced Treg infiltration was accompanied by increased CD4+ Teff accumulation and improved tumor control. Treg-specific P2RX7-KO mice exhibited reduced tumor growth, confirming a Treg-intrinsic role of P2RX7. Suppression assays revealed that tumor-infiltrating wild-type Tregs had greater suppressive activity compared with P2RX7-KO Tregs, which failed to inhibit type 1 and follicular helper T–like responses. This was associated with increased tumor-specific IgG production by lung B cells in P2RX7-KO mice. We also observed that wild-type Tregs expressed higher levels of the immunosuppressive molecule CTLA-4 when compared with P2RX7-KO Tregs. Thus, we conclude that P2RX7 expression on Tregs is essential for their suppressive function in lung cancer and targeting P2RX7 may constitute a strategy to improve lung cancer treatment by alleviating Treg-mediated immune suppression.

Background: The AFFINITY trial (NCT05890872) is a prospective, non-randomized, open-label, single-arm study evaluating the safety, immunological impact, and preliminary efficacy of Aliya pulsed electric field ablation in patients with solid tumors. Thirty-one patients were enrolled; thirty received lung lesion ablation prior to continuation on standard-of-care treatment. This manuscript reports six-month local control outcomes and immunological response characteristics. Radiological outcomes were assessed using a modified RECIST 1.1, and immunological impact was evaluated via changes in peripheral blood immunocyte populations and detection of immunoglobulins (Ig) to tumor-associated antigens in serum post-ablation. Methods: Twenty-eight patients underwent radiological assessment of ablated lesions at approximately 1-, 3-, and 6-month post-ablation to evaluate local control. Peripheral blood was collected for immune monitoring using flow cytometry and to detect IgG responses to biopsy-specific and tumor-associated antigens. Results: At 6 months, two cohorts emerged: 12 received ablation only, and 16 received ablation plus systemic and/or focal therapies (radiotherapy or second ablation). In the ablation-only group, imaging showed local control in all ablated lesions (8/12 SD, 4/12 PR), suggesting local efficacy without systemic therapy in those patients. Immunophenotyping showed dynamic changes in circulating immune cells, including T and B cell activation. A subset also exhibited modulation of tumor antigen-specific IgG, indicating a systemic humoral response. Conclusions: This analysis provides preliminary evidence that this form of ablation may promote local tumor control and modulate systemic immune function. These findings support the immunogenic potential of this specialized energy and warrant further investigation. Extended 12-month data for the full cohort will be reported in a future manuscript.

ABSTRACTTherapeutic treatment of lung nodules by ablation is a new field. Even though not considered standard of care, lung nodule ablation can be appropriate for select cases. Even though ablation is a safe and well‐tolerated procedure, bleeding is a potential complication. We introduce our stepwise approach through two cases on how we AIM (Anticipate/Adjust, Image, Manage) to prevent uncontrolled bleeding during Robotically Assisted Bronchoscopic Ablation: 1. Anticipate structures with high risk for bleeding and adjust accordingly, accounting for the needle ablation field; 2. Image: utilise cone beam CT before the first and after each ablation session to screen for bleeding; 3. Manage bleeding by pre‐emptively utilising Fogarty balloon occlusion.

Background: To evaluate the safety of Aliya pulsed electric field (PEF) ablation in lung lesions at the time of biopsy before first-line standard of care (SOC) therapy in patients with metastatic cancer. Methods: Eligible patients requiring diagnostic biopsy for suspected metastatic lung lesions were enrolled. Treatment-naive lesions ≤5 cm were PEF ablated bronchoscopically or percutaneously. Procedure and/or device-related adverse events (AE) or serious adverse events (SAEs) and their effects on subsequent therapy were assessed from PEF ablation through 30 days. Results: Forty-four lesions from 30 enrolled patients were ablated using PEF with 3-dimensional image guidance immediately following diagnostic biopsy under general anesthesia. Ninety percent (27/30) were ablated bronchoscopically with robotic navigation. One to 3 lesions (range: 0.4 to 2.4 cm longest diameter) were ablated per patient, including 17 within 1 cm of the pleura or a fissure. One procedure-related SAE (pneumothorax) occurred at the time of percutaneous biopsy and PEF ablation and resolved without sequelae. No AE impacted planned therapy initiation. Limited changes to the lung parenchyma in and around the PEF ablation zone were observed on CT scans 30 days post-PEF ablation. Conclusion: This study demonstrates PEF ablation of lung lesions at the time of diagnostic biopsy is safe. One PEF-related SAE occurred within 30 days of PEF and resolved without sequelae. Ablation adjacent to sensitive structures was feasible, safe, and without impact on subsequent therapy.

ABSTRACTAlthough current treatment strategies for nonmalignant airway stenosis may offer short‐term relief, their effectiveness is limited by high recurrence rates, often requiring additional procedures. While paclitaxel‐coated balloons (PCB) have demonstrated effectiveness in treating stenosis across various vascular and nonvascular conditions, their evidence in recurrent airway stenosis remains limited. Here, we present the case of a 35‐year‐old female with bronchial stenosis who underwent multiple bronchoscopic interventions, all of which were complicated by restenosis. Following the addition of a PCB to the therapeutic regimen, the patient achieved sustained airway patency.

Abstract Introduction Chronic obstructive pulmonary disease involves an unregulated inflammatory process that leads to the destruction and remodeling of lung architecture, potentially resulting in air-filled lesions known as bullae. We outline a novel technique for transbronchial decompression of a bulla using robotic-assisted bronchoscopy (RAB) in a patient with intraparenchymal emphysematous bullae. Case Description A 74-year-old woman with a medical history significant for COPD, Sjögren's disease, and former smoker, presented to our outpatient clinic with progressively worsening exertional dyspnea over the past two years. The patient underwent a thymectomy for thymic hyperplasia where a right middle bulla was incidentally identified. Posterior bullectomy was not performed intraoperatively due to severe pleural adhesions and the high risk of lung injury during dissection. High-resolution chest computed tomography revealed diffuse subpleural bullous changes, with asymmetric high-attenuation mural foci in several cysts (Figure 1A), with a total volume of 124.11 cm3. Given the high surgical risk, a bronchoscopic approach was decided. Bullae needle aspiration was performed under RAB guidance. Decompression was accomplished using PleurX catheter drainage (Pleur-Evac, Telfex, USA). The connection between the robot and the drainage system utilized a 3-way stopcock (Merit Medical Systems, USA) and a 30 cm vinyl connecting tube (Cook Incorporated, USA). Suction through water seal suction was performed at 20mmHg for 5 min, during which we observed bullae reduction with live intraprocedural mobile CT images. The robot was then retracted, and a 4.0 mm Zephyr endobronchial valve was deployed in the superior segment of the right middle lobe to promote atelectasis, no immediate complications were reported. Post-procedural chest CT demonstrated a significant reduction in bullae size as shown in Figure 1B. At the one-month follow-up, chest X-ray imaging revealed increased atelectasis and persistent collapse in the previously identified area of cystic change. By the two-month follow-up, pulmonary function tests indicated nonspecific ventilatory impairment, with improvements in FEV1% (from 70.5% to 78.2%) and FVC% (from 80.5% to 90.2% of the predicted values). Subsequent follow-ups have demonstrated clinical improvement in the patient's symptoms. Conclusion We contribute to the literature by introducing a novel, non-invasive technique for managing bullae with RAB in patients who are not candidates for surgery. Further studies are warranted to standardize this technique and assess its broader applicability. Figure 1. High-resolution computed tomography showing pre- and post-procedure views of the bullae. (A) Coronal and sagittal views showing the right middle lobe bullae. (66x81mm) (B) Post-procedure view of the chest HRCT (17x29 mm)

Abstract Background: Expiratory central airway collapse (ECAC) is defined by excessive inward bulging of either posterior tracheobronchial membrane or anterolateral cartilage. ECAC commonly coexists with COPD, asthma, GERD, and obstructive sleep apnea. ECAC association with bronchiectasis is yet to be documented. Common conditions leading to bronchiectasis are obstructive lung diseases predisposing to recurrent infections, cystic fibrosis, COPD, or idiopathic. This study aims to evaluate the occurrence of bronchiectasis in patients with ECAC as the primary outcome and the correlation between the severity of bronchiectasis and the severity of ECAC as a secondary outcome. Methods: A retrospective single-center study evaluated patients diagnosed with ECAC using dynamic bronchoscopy in Mayo Clinic, Florida, from June 2019 to December 2020. Radiologists analyzed dynamic, or non-contrast chest computed tomography (CT) scans to evaluate the presence of bronchiectatic changes and the prevalence of bronchiectasis in this population. Bronchiectatic changes were documented using the Brody scoring system which recorded the bronchiectasis size, extent and tree in bud appearance in individual lobes. The final score had a range from 0 to 72. The bronchiectasis scores for individual lung lobes were analyzed to interpret distribution of bronchiectasis in ECAC population. The combined bronchiectasis scores of severe ECAC and non-severe ECAC cohorts were compared to assess if severe ECAC had higher bronchiectatic involvement. Results: Out of the 166 patients diagnosed with ECAC through dynamic bronchoscopy, 133 patients (80.1%) presented bronchiectatic changes in their CT scans. Of the 59 patients with severe ECAC, 51 patients (86.4%) were diagnosed with bronchiectasis. Of the 107 patients with non-severe ECAC, 82 (76.6 %) had bronchiectasis. The mean bronchiectasis scores are greater in right and left lower lobes, followed by middle lobes. The median values between severe and non-severe ECAC were 3 and 3 respectively with a p value of 0.34. The inter quartile range was 9 in severe ECAC group and 6 in non-severe ECAC (graph 1). Discussion: The outcomes of this study showed a significant presence of bronchiectatic changes in the ECAC population, implying the importance of evaluating for other pathologies. It can signify a pathological process similar to other pathologies which predispose to recurrent infections except for cystic fibrosis, which has an upper lobe involvement. The correlation of severity between ECAC and bronchiectasis requires more studies with a larger cohort for significant outcomes.