BACKGROUND:Upper tracheal stenosis (UTS) is a rare process with multiple causes and variable approaches to treatment. Australian data on management patterns are lacking and patient resources reflecting local practices are scarce. AIMS:To describe the management strategies of UTS over 12 years among three teaching hospitals in New South Wales, Australia. A secondary aim is to formulate an evidence-based patient information sheet for this condition and its management. METHODS:Retrospective descriptive case series. Demographic, procedural and spirometric data were obtained from the medical records of patients undergoing bronchoscopy for UTS between March 2012 and February 2024. RESULTS:A total of 31 patients (81% female) underwent 120 procedures (median: 3; interquartile range: 1-5) with a median procedure interval of 134 days. The interventions included 82 balloon dilatations, 37 steroid injections, 54 radial incisions (28 endoscopic scissors, 26 laser) and seven stent insertions. Following serial procedures, there were improvements in mean maximum forced expiratory flow (FEFmax) by 1.62 L/s (95% CI: 1.05-2.15, P < 0.001) and FEFmax percent predicted by 27% (95% CI: 18-36, P < 0.001). The mean FEV1 improved by 0.36 L (95% CI: 0.15-0.54, P = 0.002) and 14% predicted. There was a documented improvement in symptoms in 80% of therapeutic procedures. Complications were infrequent and higher in procedures involving stents. Based on these findings, a patient information sheet has been developed. CONCLUSIONS:Patients with UTS undergo several bronchoscopies that result in improvements in symptoms and function with relatively low rates of complications.

Background:Pneumothorax with persistent air leak (PAL) is a debilitating condition. Patients with PAL often require prolonged chest drainage, with associated complications, such as, hospital-acquired infections, thromboembolism, and deconditioning. Endobronchial valves (EBVs) are an approved bronchoscopic treatment for PAL and may allow earlier chest tube removal and hospital discharge. Current evidence supporting the use of EBV is limited to case series and uncontrolled studies. EBVs are usually used as a last resort when other treatments failed. Whether early referral for EBV placement is feasible and can reduce hospital length of stay in patients with pneumothorax and PAL has not been tested in a randomised controlled trial (RCT). Methods:EVAPoRATe is a prospective, open-labelled, pilot, multi-centre RCT. Forty patients with pneumothorax of any cause and PAL who are unsuitable for or unwilling to undergo surgical management will be randomised 1:1 to the Early EBV Referral arm or the Standard Care arm. Patients in the Early EBV Referral arm will be assessed by an interventional clinician for EBV placement at the earliest feasible time from Day 5 of pneumothorax. Patients allocated to the Standard Care arm will receive conventional management by the attending team; EBV is allowed if clinically appropriate when air leak persists after 12 days. Participants will be followed for 6 months after discharge. Discussion:The primary outcome is the feasibility of the trial protocol, assessed by recruitment rate, adherence to the intervention arm, and retention at follow-up. Secondary outcomes include total hospital length of stay, PAL-related length of stay, interventions for PAL and EBV complications, time to air leak cessation, time to chest drain removal, pneumothorax recurrence, adverse events and serious adverse events, removal of EBVs, performance status, and mortality. This pilot feasibility study will assess whether a future full-scale RCT of EBV for PAL is practical and will provide data to guide protocol refinement and sample size calculation. Trial Registration:Australian New Zealand Clinical Trials Registry: ACTRN12625000360415; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=388086&isReview=true.

MET exon 14 skipping mutation (METex14) is a key oncogenic driver in 2% of non-small cell lung carcinoma (NSCLC) and is enriched in sarcomatoid carcinoma (SAC). However, the prevalence and significance of METex14 NSCLC in the Australian population is not known. We evaluated the incidence, clinical, molecular, and histopathological features of METex14 and SAC cases in an Australian tertiary referral centre. We retrospectively analysed clinical, molecular, histopathological, and immunohistochemical data of NSCLC cases undergoing DNA and/or RNA fusion panel next-generation sequencing (NGS) between 1 July 2021 and 15 May 2024. Among 1267 NSCLC, 880 (69%) cases had DNA NGS only, 359 (28%) cases had both DNA NGS and RNA fusion panel, and 28 (2%) cases had RNA fusion panel only. Overall, 29 (2.3%) cases had METex14, 14 (1.1%) had MET amplification, and 10 (0.8%) had MET R988C. Of the 29 METex14 patients, 15 (52%) were women and 14 (48%) were men. METex14 patients were older than those who were MET wild-type, or with EGFR or KRAS mutations (median age 76 vs 71, 69, and 71, respectively) and were less likely to be smokers than KRAS-mutated cases (58% vs 92%, p<0.0001). Most METex14 cases were adenocarcinomas (76%), with 14% classified as SAC. Programmed death-ligand 1 (PD-L1) expression was higher in METex14 than in EGFR-mutated cases. Median survival for METex14 patients was 26 months (stage I), not reached (stage II), 8 months (stage III), and 3.5 months (stage IV). Among 28 SAC cases, 57% harboured oncogenic mutations, including KRAS (18%), METex14 (14%), BRAF V600E (7%), and EGFR exon 19 deletion (4%). SAC exhibited significantly higher PD-L1 expression (mean tumour proportion score 71 vs 30, p<0.0001) and a greater proportion of high PD-L1 expressors (82% vs 30%, p<0.0001) than other NSCLC subtypes. Stage IV SAC patients had a median survival of only 2 months. In summary, in our cohort of NSCLC, METex14 mutation was found in 2% of cases using DNA NGS alone ​and up to 3% when both DNA NGS and RNA fusion panel testing were employed. METex14 mutations were more common in elderly patients, with an equal gender distribution and a high proportion of non-smokers. While most cases were adenocarcinomas, SAC was enriched for METex14. SAC was an aggressive NSCLC subtype, with KRAS and METex14 as the most common driver mutations. Given the high prevalence of PD-L1 expression in SAC, further research on immunotherapy efficacy in this group is warranted.

Rationale: Despite advancements in emphysema treatment, high morbidity and mortality rates highlight the need for innovative therapies. Hyperinflation is particularly significant for patients with emphysema as it is the main contributor to dyspnea, and much of the associated morbidity. To address this, a novel self-expanding nitinol airway scaffold was designed to alleviate lung hyperinflation by connecting emphysematous parenchyma with central bronchi, allowing trapped air to escape. Placed via a bronchoscope, the airway scaffold spans the native bronchial tree, with one end positioned in emphysematous lung tissue and the other in a more central bronchus. Methods: We conducted a pooled analysis of two studies (BREATHE-1 in Australia and BREATHE-2 in Europe) involving patients with heterogeneous or homogeneous emphysema treated bronchoscopically with up to three permanent airway scaffolds per lung performed over one or two procedures. The main objectives were to prospectively assess the feasibility, safety, and initial outcomes of the airway scaffolds in treating emphysema-related hyperinflation. The primary outcome was safety, measured by assessment of device- and/or procedure-related serious adverse events (SAEs) through six months. Secondary outcomes were technical feasibility, improvements in pulmonary function, quality of life, symptoms and exercise capacity at 3- and 6-months, and airway patency assessment by high-resolution computed tomography (CT). Results: 60 severe emphysema patients (33F/27M; mean age 65±8 years; mean RV percent predicted 255±47%) were included. 98 procedures were performed and 328 airway scaffolds were successfully placed. Thirteen patients (21.7%) experienced at least one related SAE within the 6-months following the initial procedure including pneumonia (10.0%) and COPD exacerbation (5.0%), with no pneumothoraxes. The technical success rate (successful deployment in the targeted airway as assessed by the investigator) was 92.4%. Residual volume (RV) improved by a mean decrease from baseline of 866±862 ml at 3-months and 753±874 ml at 6-months (p<0.0001). Significant improvements were also observed in spirometry, quality of life, symptoms and exercise capacity. Quantitative assessment of post-treatment CTs demonstrated preserved airway patency through 6-months in the majority of evaluable airways. Conclusions: Treatment with self-expanding nitinol airway scaffolds in emphysema patients is technically feasible and has an acceptable safety profile. Clinically meaningful and statistically significant reductions of hyperinflation were achieved at 3- and 6-months after treatment, with concurrent improvements in pulmonary function, exercise capacity and quality of life.

The increasing adoption of lung cancer screening programs and advancements in imaging technologies has significantly increased the detection of pulmonary nodules, both incidentally and through screening. This document provides a comprehensive guide for clinicians to address the complexities of managing indeterminate pulmonary nodules (IPNs), emphasising person-centred and multidisciplinary care. IPNs are categorised based on size and morphology, with specific guidelines for malignancy risk stratification, diagnostic evaluation, and follow-up. Dedicated lung nodule evaluation teams (LNETs) and nodule multidisciplinary meetings (MDMs) play a critical role in ensuring guideline adherence, streamlining the diagnostic pathway, reducing unnecessary investigations, and improving outcomes. Structured IPN programs have demonstrated benefits in early lung cancer detection, improved detection of early-stage lung cancer, and reduced delays to treatment initiation. Effective management strategies include use of standardised reporting templates, utilising validated risk models such as the PanCan malignancy risk model and agreed protocols for follow up of IPNs. This document highlights the importance of accessing prior imaging to assess for growth and accounting for technical differences between computed tomography (CT) scans. Any nodule considered to be growing requires discussion at a nodule MDM with decision to act for tissue biopsy as appropriate. A nodule MDM will assist in optimising the safest and most efficient biopsy techniques based on nodule characteristics and risk profile. By integrating multidisciplinary expertise and adhering to evidence-based protocols, services can improve the timely diagnosis and management of IPNs, minimise over-investigation, reduce chance of overdiagnosis and ultimately enhance patient outcomes and lung cancer survival.

The increasing adoption of lung cancer screening programs and advancements in imaging technologies has significantly increased the detection of pulmonary nodules, both incidentally and through screening. This document provides a comprehensive guide for clinicians to address the complexities of managing indeterminate pulmonary nodules (IPNs), emphasising person-centred and multidisciplinary care. IPNs are categorised based on size and morphology, with specific guidelines for malignancy risk stratification, diagnostic evaluation, and follow-up. Dedicated lung nodule evaluation teams (LNETs) and nodule multidisciplinary meetings (MDMs) play a critical role in ensuring guideline adherence, streamlining the diagnostic pathway, reducing unnecessary investigations, and improving outcomes. Structured IPN programs have demonstrated benefits in early lung cancer detection, improved detection of early-stage lung cancer, and reduced delays to treatment initiation. Effective management strategies include use of standardised reporting templates, utilising validated risk models such as the PanCan malignancy risk model and agreed protocols for follow up of IPNs. This document highlights the importance of accessing prior imaging to assess for growth and accounting for technical differences between computed tomography (CT) scans. Any nodule considered to be growing requires discussion at a nodule MDM with decision to act for tissue biopsy as appropriate. A nodule MDM will assist in optimising the safest and most efficient biopsy techniques based on nodule characteristics and risk profile. By integrating multidisciplinary expertise and adhering to evidence-based protocols, services can improve the timely diagnosis and management of IPNs, minimise over-investigation, reduce chance of overdiagnosis and ultimately enhance patient outcomes and lung cancer survival.

BACKGROUND:Lung cancer is a heterogeneous disease and the primary cause of cancer-related mortality worldwide. Somatic mutations, including large structural variants, are important biomarkers in lung cancer for selecting targeted therapy. Genomic studies in lung cancer have been conducted using short-read sequencing. Emerging long-read sequencing technologies are a promising alternative to study somatic structural variants, however there is no current consensus on how to process data and call somatic events. In this study, we preformed whole genome sequencing of lung cancer and matched non-tumour samples using long and short read sequencing to comprehensively benchmark three sequence aligners and seven structural variant callers comprised of generic callers (SVIM, Sniffles2, DELLY in generic mode and cuteSV) and somatic callers (Severus, SAVANA, nanomonsv and DELLY in somatic modes). RESULTS:Different combinations of aligners and variant callers influenced somatic structural variant detection. The choice of caller had a significant influence on somatic structural variant detection in terms of variant type, size, sensitivity, and accuracy. The performance of each variant caller was assessed by comparing to somatic structural variants identified by short-read sequencing. When compared to somatic structural variants detected with short-read sequencing, more events were detected with long-read sequencing. The mean recall of somatic variant events identified by long-read sequencing was higher for the somatic callers (72%) than generic callers (53%). Among the somatic callers when using the minimap2 aligner, SAVANA and Severus achieved the highest recall at 79.5% and 79.25% respectively, followed by nanomonsv with a recall of 72.5%. CONCLUSION:Long-read sequencing can identify somatic structural variants in clincal samples. The longer reads have the potential to improve our understanding of cancer development and inform personalized cancer treatment.

KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed.From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features.Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant.KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.

The complete removal of a pulmonary hydatid cyst by bronchoscopy occurs rarely in clinical practice. We describe a 22-year-old male originally from Lebanon, with suspected hydatid cyst rupture on computed tomography chest after experiencing sudden onset fevers and cough whilst taking empiric anthelmintic therapy. Bronchoscopy revealed white gelatinous material in the posterior segment of the left lower lobe. The complete membranes of a hydatid cyst were removed with grasping forceps. Histologic examination confirmed the diagnosis of echinococcosis.

Bronchopleural fistula (BPF) is a known complication of necrotizing pneumonia that is treated primarily with pleural drainage and antimicrobial therapy, while surgical treatments are generally reserved for those who do not respond to conservative management.Endobronchial spigots -a potentially less invasive approach to the treatment of bronchial occlusioncan be utilized when the culprit bronchi can be isolated and successfully blocked.We describe here the case of a 44-year-old female with a persistent right lower lobe bronchopleural fistula complicating necrotizing MRSa pneumonia, despite pleural drainage and directed antimicrobial therapy.The use of an endobronchial spigot for the bronchial occlusion of two bronchopulmonary segments led to an immediate reduction in the size of a large pleural cavity, contributing to significant symptomatic and biochemical improvement.The treatment can thus be considered an alternate cost-effective minimally invasive approach to the management of non-resolving bronchopleural fistula.

BACKGROUND AND OBJECTIVE:As the presentation of pulmonary nodules increases, the importance of a safe and accurate method of sampling peripheral pulmonary nodules is highlighted. First-generation robotic bronchoscopy has successfully assisted navigation and improved peripheral reach during bronchoscopy. Integrating tool-in-lesion tomosynthesis (TiLT) may further improve yield. METHODS:We performed a first-in-human clinical trial of a new robotic electromagnetic navigation bronchoscopy system with integrated digital tomosynthesis technology (Galaxy System, Noah Medical). Patients with moderate-risk peripheral pulmonary nodules were enrolled in the study. Robotic bronchoscopy was performed using electromagnetic navigation with TiLT-assisted lesion guidance. Non-specific results were followed up until either a clear diagnosis was achieved or repeat radiology at 6 months demonstrated stability. RESULTS:Eighteen patients (19 nodules) were enrolled. The average lesion size was 20 mm, and the average distance from the pleura was 11.6 mm. The target was successfully reached in 100% of nodules, and the biopsy tool was visualized inside the target lesion in all cases. A confirmed specific diagnosis was achieved in 17 nodules, 13 of which were malignant. In one patient, radiological monitoring confirmed a true non-malignant result. This translates to a yield of 89.5% (strict) to 94.7% (intermediate). Complications included one pneumothorax requiring observation only and another requiring an overnight chest drain. There was one case of severe pneumonia following the procedure. CONCLUSION:In this first-in-human study, second-generation robotic bronchoscopy using electromagnetic navigation combined with integrated digital tomosynthesis was feasible with an acceptable safety profile and demonstrated a high diagnostic yield for small peripheral lung nodules.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often the only source of tumor tissue from patients with advanced, inoperable lung cancer. EBUS-TBNA aspirates are used for the diagnosis, staging, and genomic testing to inform therapy options. Here we extracted DNA and RNA from 220 EBUS-TBNA aspirates to evaluate their suitability for whole genome (WGS), whole exome (WES), and comprehensive panel sequencing. For a subset of 40 cases, the same nucleic acid extraction was sequenced using WGS, WES, and the TruSight Oncology 500 assay. Genomic features were compared between sequencing platforms and compared with those reported by clinical testing. A total of 204 aspirates (92.7%) had sufficient DNA (100 ng) for comprehensive panel sequencing, and 109 aspirates (49.5%) had sufficient material for WGS. Comprehensive sequencing platforms detected all seven clinically reported tier 1 actionable mutations, an additional three (7%) tier 1 mutations, six (15%) tier 2–3 mutations, and biomarkers of potential immunotherapy benefit (tumor mutation burden and microsatellite instability). As expected, WGS was more suited for the detection and discovery of emerging novel biomarkers of treatment response. WGS could be performed in half of all EBUS-TBNA aspirates, which points to the enormous potential of EBUS-TBNA as source material for large, well-curated discovery-based studies for novel and more effective predictors of treatment response. Comprehensive panel sequencing is possible in the vast majority of fresh EBUS-TBNA aspirates and enhances the detection of actionable mutations over current clinical testing.

The traditional indications for lobectomy for resectable Non‐small Cell Lung Cancer (NSCLC) may be set to change. Recently, anatomical segmentectomy (AS) versus lobectomy as an approach for early‐stage NSCLC has been described in phase 3 randomised controlled trials. The demand for methods to facilitate AS may increase as a consequence. We describe three cases of AS using the combination of endobronchial infiltration of indocyanine green (ICG) to identify the intersegmental plane (critical for the performance of AS), and Computed Tomography (CT) guided methylene blue injection for lesion localisation. The operations were completed successfully demonstrating satisfactory post‐operative outcomes including lesion resection with clear surgical margins and acceptable length of stay. We believe that endobronchial instillation of ICG and CT‐guided methylene blue injection for lesion localisation show promise as a technique to complement parenchymal sparing thoracic oncological surgery.