Cryoablation and immunity in non-small cell lung cancer: a new era of cryo-immunotherapy.

Despite remarkable advances in tumor response and patient survival in the past decade, systemic immunotherapies for lung cancer result in an objective response in only around half of patients treated. On the basis of this limitation, combination strategies are being investigated to improve response rates. Cryoablation has been proposed as one such technique to induce immunogenic cell death and synergize with systemic immunotherapies, including immune checkpoint inhibitors. Cryoablation has been traditionally delivered percutaneously with imaging guidance although recent technological advances allow for bronchoscopic delivery. Herein, we review the pre-clinical and clinical evidence for the use of cryoablation in non-small cell lung cancer and potential induction of anti-tumor immunity. We highlight ongoing studies involving this approach and propose areas of future investigation.

Safety and utility of indwelling pleural catheters in lung transplant recipients.

INTRODUCTION: The safety and efficacy of indwelling pleural catheters (IPCs) in lung allograft recipients is under-reported. METHODS: We performed a multicenter, retrospective analysis between 1/1/2010 and 6/1/2022 of consecutive IPCs placed in lung transplant recipients. Outcomes included incidence of infectious and non-infectious complications and rate of auto-pleurodesis. RESULTS: Seventy-one IPCs placed in 61 lung transplant patients at eight centers were included. The most common indication for IPC placement was recurrent post-operative effusion. IPCs were placed at a median of 59 days (IQR 40-203) post-transplant and remained for 43 days (IQR 25-88). There was a total of eight (11%) complications. Infection occurred in five patients (7%); four had empyema and one had a catheter tract infection. IPCs did not cause death or critical illness in our cohort. Auto-pleurodesis leading to the removal of the IPC occurred in 63 (89%) instances. None of the patients in this cohort required subsequent surgical decortication. CONCLUSIONS: The use of IPCs in lung transplant patients was associated with an infectious complication rate comparable to other populations previously studied. A high rate of auto-pleurodesis was observed. This work suggests that IPCs may be considered for the management of recurrent pleural effusions in lung allograft recipients.

Updates in percutaneous tracheostomy and gastrostomy: should we strive for combined placement during one procedure?

PURPOSE OF REVIEW: Percutaneous tracheostomy and gastrostomy are minimally invasive procedures among the most common performed in intensive care units. Practices across centres vary considerably, and questions remain about the optimal timing, performance and postoperative care related to these procedures. RECENT FINDINGS: The COVID-19 pandemic has triggered a reevaluation of the practice of percutaneous tracheostomy and gastrostomy in the ICU. Combined percutaneous tracheostomy and gastrostomy at the bedside has potential benefits, including improved nutrition, decreased exposure to anaesthetics, decreased patient transport and decreased hospital costs. Percutaneous ultrasound gastrostomy is a novel technique that eliminates the need for an endoscope that may allow intensivists to perform gastrostomy at the bedside. SUMMARY: Multidisciplinary care is essential to the follow up of critically ill patients receiving tracheostomy and gastrostomy. Combined tracheostomy and gastrostomy has numerous potential benefits to patients and hospital systems. Interventional pulmonologists are uniquely qualified to perform both procedures and serve on a tracheostomy and gastrostomy team.

Safety and Feasibility of a Sheath Cryoprobe for Bronchoscopic Transbronchial Biopsy: The FROSTBITE Trial.

BACKGROUND: Bronchoscopic lung biopsy is typically performed using transbronchial forceps. However, this method is limited by small sample size and presence of crush artifact. Cryobiopsy offers the potential to overcome these limitations with larger artifact-free samples but has not been widely adopted due to concerns over increased rates of bleeding and pneumothorax. A new, smaller 1.1-mm cryoprobe has been developed that operates in a similar fashion to forceps, though the safety profile of this cryoprobe has not yet been prospectively studied. OBJECTIVE: The aim of this study was to investigate the safety of transbronchial biopsy using a novel 1.1-mm cryoprobe. METHODS: This prospective, single-arm study enrolled patients referred for transbronchial biopsy. All procedures were performed using the 1.1-mm cryoprobe with oversheath. The primary outcome was the composite of significant complications related to the cryobiopsy procedure (bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure). Bleeding and pneumothorax were graded according to previously published scales. RESULTS: Fifty participants from two academic medical centers underwent transbronchial cryobiopsy. Indications for biopsy included evaluation of lung transplant allograft (50%), diffuse lung disease (44%), and pulmonary parenchymal lesion (6%). There were two pneumothoraces (4%), neither of which required aspiration or chest tube placement. There were no Grade 3 or 4 bleeding events. Mild bleeding (Grade ≤2) was observed in 25 cases (50%). No complications occurred that met the a priori primary outcome of bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure. CONCLUSIONS: Transbronchial cryobiopsy using a 1.1-mm cryoprobe is feasible with an acceptable safety profile.

Applications of cryobiopsy in airway, pleural, and parenchymal disease.

INTRODUCTION: Cryobiopsy is a novel diagnostic technique for thoracic diseases, which has been extensively investigated over the past 20 years. It was originally proposed for the diagnosis of endobronchial lesions and diffuse parenchymal lung disease due to limitations of conventional sampling techniques including small size and presence of artifacts. AREAS COVERED: We review recent evidence related to the expanding use of cryobiopsy in thoracic diseases. To identify references, the MEDLINE database was searched from database inception until May 2022 for case series, cohort studies, randomized controlled trials, systematic reviews, and meta-analyses related to cryobiopsy. EXPERT OPINION: Cryobiopsy has expanding applications in the field of thoracic diseases. Evidence to support transbronchial cryobiopsy as an alternative to surgical lung biopsy is increasing and was recently endorsed as a conditional recommendation by the latest American Thoracic Society guideline update for Idiopathic Pulmonary Fibrosis. Developments in technology and technique, in particular the availability of a 1.1 mm flexible cryoprobe, have extended applications to pulmonary diseases, including diagnosis of interstitial lung diseases, peripheral pulmonary lesions, and lung transplant rejection.

Accuracy of Pulmonary Nodule Sampling Using Robotic Assisted Bronchoscopy with Shape Sensing, Fluoroscopy, and Radial Endobronchial Ultrasound (The ACCURACY Study).

BACKGROUND: Despite recent advances in guided bronchoscopy, the yield of bronchoscopic biopsy of a peripheral pulmonary nodule (PPN) remains highly variable. OBJECTIVE: The aim of the study was to evaluate which features of robotic assisted bronchoscopy (RAB) contribute to a successful biopsy in a cadaver model. METHODS: A preclinical, prospective, single-blinded trial using a ventilated human cadaveric model assessed the successful puncture of implanted pulmonary nodules using various localization techniques with RAB. The different approaches included positioning the robotic catheter at predefined distances from the target nodule (<10 mm, 10-20 mm, 20-30 mm), bronchoscopist correction of divergence between the software virtual map and bronchoscopic view if observed, and impact of fluoroscopy and radial endobronchial ultrasound (rEBUS). The primary endpoint was a central target hit (defined as an inner 2/3 target puncture) verified by cone-beam computed tomography. RESULTS: Thirty-eight RAB procedures were performed to target 16 PPNs. Median nodule size was 16.2 mm. All targets were located in the outer 1/3 of the lung with a bronchus sign in 31.3%. Central target hit rates were improved when the robotic catheter tip was closer to the nodule (<10 mm 68%, 10-20 mm 66%, 20-30 mm 11%, p < 0.001). Multivariable analysis confirmed the strongest predictor of a central target hit was robotic catheter distance to nodule (OR 0.89 per increase in 1 mm, p < 0.001), independent of the presence of a bronchus sign, divergence or concentric rEBUS view. CONCLUSIONS: Utilizing a RAB platform, closer proximity of the robotic catheter to the target nodule results in an increase in peripheral nodule biopsy success.

Management of Pneumothorax.

Pneumothorax is a common medical condition encountered in a wide variety of clinical presentations, ranging from asymptomatic to life threatening. When symptomatic, it is important to remove air from the pleural space and provide re-expansion of the lung. Additionally, patients who experience a spontaneous pneumothorax are at high risk for recurrence, so treatment goals also include recurrence prevention. Several recent studies have evaluated less invasive management strategies for pneumothorax, including conservative or outpatient management. Future studies may help to identify who is greatest at risk for recurrence and direct earlier definitive management strategies, including thoracoscopic surgery, to those patients.

Bronchoscopic intratumoural therapies for non-small cell lung cancer.

The past decade has brought remarkable improvements in the treatment of non-small cell lung cancer (NSCLC) with novel therapies, such as immune checkpoint inhibitors, although response rates remain suboptimal. Direct intratumoural injection of therapeutic agents via bronchoscopic approaches poses the unique ability to directly target the tumour microenvironment and offers several theoretical advantages over systemic delivery including decreased toxicity. Increases in understanding of the tumour microenvironment and cancer immunology have identified many potential options for intratumoural therapy, especially combination immunotherapies. Herein, we review advances in the development of novel bronchoscopic treatments for NSCLC over the past decade with a focus on the potential of intratumoural immunotherapy alone or in combination with systemic treatments.

Yield of Malignant Pleural Effusion for Detection of Oncogenic Driver Mutations in Lung Adenocarcinoma.

BACKGROUND: Pleural fluid can be used to assess targetable mutations in patients with lung adenocarcinoma. The primary objective of this study was to assess the yield of pleural fluid cytology for targetable oncogenic mutations (EGFR, KRAS, BRAF, ALK, and ROS1 gene rearrangements). We also assessed pleural fluid volume necessary for molecular testing. METHODS: Retrospective review was performed of 134 consecutive patients with lung adenocarcinoma associated malignant pleural effusions. EGFR and KRAS testing was done using PCR amplification followed by DNA sequencing, or next generation sequencing in more recent cases that included BRAF assessment. Fluorescence in situ hybridization employing break-apart probes was used to test for ALK and ROS1 rearrangements. RESULTS: Mutation analysis on pleural fluid cell-block was performed on 56 patients. It was adequate for complete analysis ordered including EGFR, KRAS, BRAF, ALK, and ROS1 rearrangements on 40 (71.4%) samples. For individual mutations, EGFR testing was possible in 38 of 49 (77.6%); KRAS 22 of 28 (78.6%); BRAF 10 of 13 (76.9%), ALK gene rearrangement 42 of 51 (82.4%) and ROS1 gene rearrangement in 21 of 28 (75%) pleural fluid specimens. The analysis was satisfactory in 13 of 19 (68.4%) samples with ≤100 mL versus 27 of 37 (72.9%) with >100 mL of fluid tested (P-value=0.7). CONCLUSION: Genetic mutation analysis can be performed on malignant pleural effusions secondary to lung adenocarcinoma, independent of fluid volume.