A novel HLA-DQB2::MET gene fusion variant in lung adenocarcinoma with prolonged response to tepotinib: a case report.

Background: MET rearrangements are infrequently observed in non-small cell lung cancer (NSCLC). Advanced genomic detection techniques have unveiled such infrequent genomic variations, particularly MET fusions in approximately 0.5% of NSCLC patients. Tyrosine kinase inhibitors (TKIs) have revolutionized the standard of care in lung cancer and more recently a second generation MET TKI tepotinib received Food and Drug Administration (FDA) approval for MET exon 14 alterations in metastatic NSCLC. Despite this, the therapeutic landscape for MET-rearranged NSCLC patients remains significantly unexplored. The aim of our report is to detail a unique case of a patient with metastatic lung adenocarcinoma with a novel HLA-DQB2::MET fusion detected by next-generation sequencing (NGS) following previous treatment resistance. Case Description: A 73-year-old female was initially started on carboplatin, pemetrexed and pembrolizumab with maintenance, but eventually had progression in the left upper lobe (LUL). Upon progression she was enrolled in a clinical trial of a monoclonal antibody with or without a PD-1 inhibitor, but brain metastasis progression was eventually detected by magnetic resonance imaging (MRI) requiring stereotactic radiosurgery (SRS) and a craniotomy. The trial drug was eventually discontinued due to progression and toxicity and NGS on bronchoscopy tissue revealed HLA-DQB2::MET fusion. The patient was initiated on tepotinib and continues with clinical and radiological stable disease for over 12 months. The patient's response to a MET inhibitor, tepotinib, underscores the potential efficacy of selective MET inhibitors for individuals with previously unexplored MET fusions. Conclusions: The positive response to tepotinib of a patient with NSCLC harboring a novel MET-Fusion underscores the importance of the use of comprehensive next-generational sequencing-based panels and highlights the necessity for additional research and clinical exploration of selective MET inhibitors for managing NSCLC with MET rearrangements.

Computational fluid dynamics evaluation of excessive dynamic airway collapse.

BACKGROUND: Excessive dynamic airway collapse, which is often caused by the collapse of the posterior membrane wall during exhalation, is often misdiagnosed with other diseases; stents can provide support for the collapsing airways. The standard pulmonary function tests do not necessarily show change in functional breathing condition for evaluation of these type of diseases. METHODS: Flow characteristics through a patient's airways with excessive dynamic airway collapse have been numerically investigated. A stent was placed to support the collapsing airway and to improve breathing conditions. Computed tomography images of the patient's pre- and post-stenting were used for generating 3-Dimensional models of the airways, and were imported into a computational fluid dynamics software for simulation of realistic air flow behavior. Unsteady simulations of the inspiratory phase and expiratory phase were performed with patient-specific boundary conditions for pre- and post-intervention cases to investigate the effect of stent placement on flow characteristic and possible improvements. FINDINGS: Results of post-stent condition show reduced pressure, velocity magnitude and wall shear stress during expiration. The variation in wall shear stress, velocity magnitude and pressure drop is negligible during inspiration. INTERPRETATION: Although Spirometry tests do not show significant improvements, computational fluid dynamics results show significant improvements in pre- and post-treatment results, suggesting improvement in breathing condition.

Teflon Injection into the Trachea Causes Predictable Fibroblastic Response and Collagen Deposition: A Pilot Study.

BACKGROUND: Expiratory central airway collapse is an increasingly recognized abnormality of the central airways and may be present in as many as 22% of patients evaluated for chronic obstructive pulmonary disease and/or asthma. Many current treatment options require invasive procedures that have been shown to cause significant morbidity and mortality. To test the hypothesis that Teflon injection will induce sufficient fibroblast proliferation and collagen deposition, we evaluated the time course on the effect of Teflon injection in the posterior membranous trachea on the histopathology of the tracheobronchial tree. METHODS: Six Yucatan Pigs were assigned to undergo general anesthesia and injection of 0.3 to 0.5 mL of sterile Teflon paste in 50% glycerin into the posterior membranous tracheal wall. A control pig received an equivalent volume of glycerin. Animals were euthanized in predefined intervals and tracheas were excised and examined under light microscopy for identifying fibroblast proliferation and collagen deposition. RESULTS: Compared with the control pig, the Teflon injection site showed tissue reaction of fibrohistiocytic proliferation and subsequent collagen deposition in all animals. Furthermore, the increased fibroblast proliferation and collagen deposition were time dependent (P<0.01). CONCLUSION: This pilot study demonstrates histopathologic changes in the trachea after Teflon injection, comprised of increased fibroblast activity and collagen deposition that could be of potential use in creating greater airway rigidity in patients with sever diffuse excessive dynamic airway collapse.

Successful closure of bronchopleural fistula with Xeroform dressing.

Bronchopleural fistula (BPF) is a communication between the pleural space and the bronchial tree, and is associated with significant morbidity and mortality. Treatment options for BPF include surgical closure and medical therapy. In an unstable patient, invasive surgical intervention is not an option. In this article, we report the case of a 61-year-old man who developed pneumothorax with a large BPF after a bronchoscopic resection of a malignant endobronchial lesion. We inserted a piece of 1.5×1.5-cm Xeroform dressing to seal the massive air leak with successful closure of the BPF. To our knowledge, this is the first report of successful closure of a massive BPF with Xeroform dressing in an acutely decompensating patient.