Faculty Bibliography

Background: There is growing appreciation for the role of tumordraining lymph nodes (TDLN) in the dynamic of immuno-editing orchestrated by non-small cell lung cancers (NSCLC). By comparing Tcell subsets and gene expression in TDLN and non-draining lymph nodes (NDLN), we aim to determine whether there is tumor-regional variation in immunophenotype. Method: Patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis/staging of NSCLC were recruited. Aspirates were obtained from TDLN (N1/N2 nodes with increased fluorodeoxyglucose-F-18 (FDG) avidity and/or enlarged >1cm) and NDLN (non-enlarged/non- FDG-avid N2/N3 nodes) along with peripheral blood. Samples were stained with fluorophore-conjugated antibodies (CD4-FITC, CD8-V450, CD25-PECy7, CD127-APCR700, CD45RO-PECF594) and analyzed by flow cytometry. CD4+CD25- and CD8+ effector T-cells (Teff) were sorted. Gene expression profiling was performed on sorted Teff using the NanostringTM platform to measure differential expression between TDLN and NDLNs. Result: We compared T-cell subpopulations in TDLN and paired NDLN from 16 subjects. There were significantly fewer CD4+ T-cells in TDLN vs NDLN (10.1% vs 28.9%, p=0.0039), with more Tregs (12.1% vs 7.3%, p=0.1563) suggesting a pattern of tumorregional immunosuppression in the TDLN. This was more consistent when tumor histology was adenocarcinoma compared to squamous cell cancer with respect to both depletion of Teff and higher proportion of Tregs (Fig 1). A more immunosuppressive TDLN phenotype was also observed with high tumor PD-L1 expression (>50%), with 36% fewer CD4+ T-cells in TDLN relative to paired NDLN when PD-L1 expression was high relative to just 3.2% fewer CD4+ T-cells with low PD-L1 expression. Gene expression in Teff has preliminarily demonstrated upregulation of genes mediating T-cell exhaustion (CTLA-4, PD-1, TGFb) and downregulation of co-stimulatory/recruitment factors (CD28, ICOS, ICAM2) in TDLN suggesting impaired activation of tumorregional Teff. Conclusion: Our findings suggest that TDLNs in patients with NSCLC display a tolerogenic phenotype, with more marked immunosuppression in the setting of adenocarcinoma and high tumor PD-L1 expression. (Figure Presented)

INTRODUCTION: We describe the evaluation and management of a patient with airway obstruction due to retained surgical material who was being treated as refractory asthma. CASE PRESENTATION: A 61 year old woman was referred for wheezing, dyspnea, and cough. She was steroid dependent in the setting of "poorly controlled asthma" and recurrent pneumonias. Fourteen years earlier she had undergone left lower lobectomy for "carcinoid". Given her refractory symptoms and lack of recent imaging, a CT chest was ordered. CT scan showed left mainstem obstruction. Bronchoscopy revealed complete left mainstem obstruction due to retained surgical pledgets. Extraction was not attempted given potential for major bleeding or loss of airway integrity. Intra-operative thoracic surgery consult was requested, leading to a decision to defer removal until a surgical team was available for urgent rescue completion pneumonectomy. A ventilation-perfusion (V/Q) scan was performed to characterize left lung physiology prior to interventions including relief of airway obstruction and possible completion pneumonectomy. There was decreased ventilation and perfusion of the left lung with split function of eight percent. A rigid bronchoscope was advanced into the left main bronchus. A needle knife at 20 watts was used to cut sutures retaining the pledgets and forceps were used for pledget and suture removal. The patient was extubated soon after the procedure and was discharged the following day. She was seen in follow-up and reported resolution of her symptoms and improved exercise tolerance. Repeat V/Q scan showed improved ventilation and perfusion with split function of twenty two percent. DISCUSSION: Transbronchial erosion of surgical material is rare, and literature describing removal of these foreign bodies is limited 1. Here we describe an approach including multi-disciplinary decision making, preparing for emergent complications during removal of the material, assessment of the patient's ability to tolerate foreign body removal and possible completion pneumonectomy, as well as rigid bronchoscope techniques for definitive removal. CONCLUSIONS: Foreign bodies due to transbronchial erosion are best approached with proper preparation and planning as we have described here

Establishing the etiology of exudative pleural effusions in the setting of an unrevealing pleural fluid analysis often requires biopsies from the parietal pleura. While closed pleural biopsy (CPB) has been a popular minimally-invasive approach, it has a poor diagnostic yield, barring a diagnosis of tuberculous pleurisy. Medical thoracoscopy (MT) is a minimally-invasive ambulatory procedure performed under local anesthesia or moderate sedation which allows for direct visualization of biopsy targets as well as simultaneous therapeutic interventions, including chemical pleurodesis and indwelling tunneled pleural catheter (ITPC) placement. The excellent yield and favorable safety profile of MT has led to it replacing CPB for many indications, particularly in the management of suspected malignant pleural effusions. As experience with MT amongst interventional pulmonologists has grown, there is an increased appreciation for its important role alongside percutaneous and surgical approaches in the diagnosis and treatment of pleural disease.

RATIONALE: Transbronchial cryobiopsy is an emerging technique for obtaining biopsies of lung parenchyma. Despite limited evidence of safety and efficacy in direct comparison to other available biopsy procedures, pulmonologists are integrating this technique into clinical practice with the hope of avoiding the risks of surgical lung biopsy. OBJECTIVES: To report the rate of severe complications and diagnostic outcomes immediately after introduction of transbronchial cryobiopsy into the clinical practice of a single-center, high-volume, interventional pulmonary group at a large academic medical center in the United States. METHODS: Retrospective review of a case series. RESULTS: Twenty-five consecutive patients underwent transbronchial cryobiopsy for a variety of indications over a period of 14 weeks. In the absence of a strict protocol, a variety of techniques was employed by four attending interventional pulmonologists and one advanced interventional pulmonology fellow to plan and complete the procedures. Three patients (12%) experienced serious hemorrhage immediately after biopsy, including one patient who survived a life-threatening bleed. Two procedures were complicated by an iatrogenic pneumothorax. One patient experienced hypercapnic respiratory failure shortly after the procedure. A definitive diagnosis was made on 14 cryobiopsies (56%). Another 5 biopsies (20%) contributed to a presumptive diagnosis achieved by multidisciplinary consensus. CONCLUSIONS: Transbronchial cryobiopsy may have diagnostic and safety limitations that are not yet well appreciated given the state of the published medical literature. Major questions remain regarding the safest procedural protocol to be used when performing transbronchial cryobiopsy. Thorough planning and a high degree of caution are encouraged on first introduction of this technique into a clinical practice.