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RATIONALE Outcomes of interventional lymphangiographic treatment of nontraumatic chylous pleural effusions using traditional approaches have been highly variable. Recent advances in lymphatic imaging have revealed variations in underlying pathophysiology enabling improved targeting of therapeutic interventions. OBJECTIVE To assess outcomes of an algorithm for management of nontraumatic chylous pleural effusions based on advanced MR identification of various abnormalities in the thoracoabdominal lymphatic network that give rise to chylothorax. METHODS Novel lymphatic MR imaging was performed in 52 patients ages 11 to 89 years. Three distinct pathophysiological patterns were found: (1) abnormal pulmonary lymphatic flow from the thoracic duct only; (2) abnormal pulmonary lymphatic flow from retroperitoneal lymphatic networks with or without involvement of the thoracic duct; and (3) chylous ascites presenting as chylous pleural effusion. Lymphatic interventions were individualized to the underlying pathophysiological patterns. RESULTS In 41/52 (79%) patients, imaging revealed abnormal pulmonary lymphatic flow from the thoracic duct and/or retroperitoneal lymphatic networks. Thoracic duct embolization and/or interstitial embolization of retroperitoneal lymphatic resulted in resolution of chylothorax in this group in 38/41 (93%) of those patients. Five patients experienced Grade 1 or 2 complications. One patient succumbed to post-operative stress-induced cardiomyopathy and pulmonary embolism. Chylous ascites was the cause of chylothorax in 11/52 (21%) patients. Eight chose to undergo interventions for chylous ascites with clinical success in 6/8 (75%). CONCLUSIONS Application of MRI-guided intervention algorithm resulted in successful control of non-traumatic chylothorax in 93% patients with abnormal pulmonary lymphatic flow. Appropriate treatment of chylous ascites presenting as a pleural effusion requires systematic evaluation and diagnosis prior to potential treatments.

Introduction Patients with COVID-19 ARDS require significant amounts of sedation and analgesic medications which can lead to longer hospital/ICU length of stay, delirium, and has been associated with increased mortality. Tracheostomy has been shown to decrease the amount of sedative, anxiolytic and analgesic medications given to patients. The goal of this study was to assess whether tracheostomy decreased sedation and analgesic medication usage, improved markers of activity level and cognitive function, and clinical outcomes in patients with COVID-19 ARDS. Study Design and Methods A retrospective registry of patients with COVID-19 ARDS who underwent tracheostomy creation at the University of Pennsylvania Health System or the Johns Hopkins Hospital from 3/2020 to 12/2020. Patients were grouped into the early (≤14 days, n = 31) or late (15 + days, n = 97) tracheostomy groups and outcome data collected. Results 128 patients had tracheostomies performed at a mean of 19.4 days, with 66% performed percutaneously at bedside. Mean hourly dose of fentanyl, midazolam, and propofol were all significantly reduced 48-h after tracheostomy: fentanyl (48-h pre-tracheostomy: 94.0 mcg/h, 48-h post-tracheostomy: 64.9 mcg/h, P = .000), midazolam (1.9 mg/h pre vs. 1.2 mg/h post, P = .0012), and propofol (23.3 mcg/kg/h pre vs. 8.4 mcg/kg/h post, P = .0121). There was a significant improvement in mobility score and Glasgow Coma Scale in the 48-h pre- and post-tracheostomy. Comparing the early and late groups, the mean fentanyl dose in the 48-h pre-tracheostomy was significantly higher in the late group than the early group (116.1 mcg/h vs. 35.6 mcg/h, P = .03). ICU length of stay was also shorter in the early group (37.0 vs. 46.2 days, P = .012). Interpretation This data supports a reduction in sedative and analgesic medications administered and improvement in cognitive and physical activity in the 48-h period post-tracheostomy in COVID-19 ARDS. Further, early tracheostomy may lead to significant reductions in intravenous opiate medication administration, and ICU LOS.

Noonan Syndrome is a disorder characterized by central and peripheral lymphatic conducting anomalies, leading to chylothorax, chylous ascites, and metabolic derangement. Novel imaging modalities including dynamic contrast magnetic resonance lymphangiography (DCMRL) and intranodal lymphangiography have allowed for increased visualization of lymphatic pathology. We describe the first study of a 61-year-old male with Noonan syndrome who developed severe pulmonary insufficiency and chylothoraces. DCMRL and intranodal lymphangiography demonstrated central thoracic duct (TD) occlusion. The patient's condition significantly improved following microsurgical TD-venous anastomosis assisted by TD catherization for imaging guidance, resulting in decompression of the lymphatic system and resolution of the pulmonary symptoms.

Airway complications following lung transplantation are common and difficult to manage. While a bulk of literature exists regarding the prevalence and risk factors associated development of airway complications following lung transplantation, literature guiding specific treatment options is limited. Balloon dilation alone is able to transiently relieve airway stenosis and improve symptoms though it is frequently insufficient. Treatment with airway stenting in severe disease has resulted in significant clinical improvement and can generally be removed with sustained effects. Translational studies into hypoxia-induced gene expression and the lung microbiome offer potential therapeutic targets for improved outcomes moving forward. Balloon dilation for airway stenosis should be considered first-line therapy, with consideration of ablative and topical airway therapy for more effective and sustained results. In severe cases, including dehiscence, malacia, and stenosis, stenting is often required. Silicone and covered metal stents, while sometimes necessary, are not a perfect solution and are associated with their own list of potential complications. In the absence of a robust evidence base, recognition of endoscopic airway phenotypes and the utility of the various bronchoscopic modalities available are essential for treating this complex group of patients.

Secondary pneumothorax is a rare but serious complication of allergic bronchopulmonary aspergillosis (ABPA) and bronchiectasis [1,2]. Persistent air leak (PAL) after secondary pneumothorax is an ongoing abnormal communication between bronchi or alveoli and the pleural space, despite drainage. Ongoing PAL for 5 days after initial chest tube insertion necessitates prolonged ambulatory drainage or aggressive management with video-assisted thoracoscopic surgery (VATS) or pleurodesis [3,4]. There are no randomized trials examining the efficacy of endobronchial valves (EBVs) for PAL with underlying inflammatory pulmonary disease. We describe the successful use of an EBV for PAL in a man with ABPA on high dose steroids, with a large bronchopleural fistula (BPF).

Primary airway lesions in the pediatric population are rare; however, it is important for the interventional pulmonologist to have a good understanding of the various excisional techniques and their application to the pediatric population. Lesion excision requires careful consideration to tailor specific equipment to specific anatomy, and airway caliber in the pediatric population is often the main limitation to applying those techniques to individual children. Obstruction from endobronchial tumors can require a multimodal and multidisciplinary approach. There is little data to guide the interventionalist other than clinical experience and case reports. In the following chapter the most common lesions are discussed as are the various techniques for airway lesion excision including laser ablation, mechanical excision, and cryotherapy.

Novel diagnostic techniques for lung cancer are rapidly evolving. Specifically, several novel changes to bronchoscopy are reaching clinical evaluation. It is critical to think about historical standards for evaluating new diagnostic testing, and put those concepts into the framework of lung cancer. Often a thorough evaluation of new technology is not performed as a part of regulatory marketing clearance. Therefore, we must consider how to best study novel testing beyond these regulatory minimums. There are several methodological principles that can achieve this goal such as using a control arm, more thorough reporting of enrolled patients, consecutive patient enrollment, and adequate sample size. We hope clinicians, particularly those performing bronchoscopy for lung nodules, will feel empowered to critically appraise the evaluation of new diagnostic testing for lung cancer moving forward.

Case Presentation A 67-year-old woman was referred to our institution for nonresolving pneumonia and abnormal chest images. She was in her usual state of health until 1 month prior to referral when she started having fever, chills, dry cough, and chest pain. She presented initially to an urgent care facility that diagnosed her with bilateral pneumonia and left-sided volume loss on chest radiography. She was given azithromycin, but her fever did not resolve in the weeks following the antibiotic course. Previous to these symptoms she was able to play tennis and worked full time as the director of a charter school.

Background Endobronchial ultrasound (EBUS)-guided fine needle aspiration (FNA) is performed to diagnose and stage lung cancer. Multiple studies have described the value of Rapid On-Site Evaluation (ROSE), but often the emphasis is upon diagnosis than adequacy for molecular testing (MT). The aim was to identify variable(s), especially cytology-related, that can improve MT. Methods A search for EBUS-FNAs with ROSE was conducted for lung adenocarcinomas or when this diagnosis could not be excluded. All such cases underwent reflex MT on cell blocks. The impact of cytology-related variables [i.e., number of pass(es), dedicated pass(es) directly into media, cytotechnologist (CT), laboratory technician (LT) and triage with 1 or >1 cytologist] was evaluated. The latter category was divided into Group A [ROSE, triage and slide preparation by cytopathologist (CP) and CT at start of the procedure] and Group B (ROSE only by CT or by CT/CP after start of procedure; triage and slide preparation by CT or clinical staff). The impact of all these variables on MT was assessed. Results A total of 100 cases were identified, and 79 had sufficient tissue for MT. Of all variables evaluated, MT was positively affected by performing a direct dedicated pass (P = 0.013) and ROSE by Group A (P = 0.033). Conclusions ROSE with appropriate triage, including performing a dedicated pass and proper slide preparation, improves MT, and this is enhanced by having >1 cytologist at the start of the procedure. In the era of personalized medicine, “adequate” should denote sufficient tissue for diagnosis and MT.

Background Airway complications after lung transplantation are a difficult to treat clinical entity. A subset of these patients develop progressive distal airway stenosis (DAS) and a total loss of lobar airways. Stents may be placed to prevent continued obstruction. However, there is little data to suggest stent placement provides durable airway patency or a reduction in the need for further interventions. Methods A retrospective cohort study was conducted using patients with DAS who underwent a variety of interventions. Demographic information and complications were described using nonparametric methods. Lung function at 1 year and bronchoscopies per month were compared between stented and nonstented patients using a Mann-Whitney test. For patients treated with stenting, bronchoscopies per month were compared before and after stenting using a Wilcoxon signed-rank test. Airway patency was compared between stented and nonstented patients using the Fischer exact test. Results Eleven airways were identified as DAS phenotype, 5 of which were treated with stents. Within the stented airways, a trend toward an increase in bronchoscopies per month was seen after stent placement. Comparing the stented versus nonstented patients, there was no improvement in lung function, no reduction in bronchoscopies per month, and no difference in airway patency for stented patients. Conclusion Patients with DAS phenotypes that were treated with endobronchial stenting did not require less airway intervention or have greater final airway patency compared with the nonstented airways. Among the stented patients, the need for airway manipulation did not decrease after stent placement.

Cryotherapy is an evolving therapeutic and diagnostic tool used during bronchoscopy. Through rapid freeze-thaw cycles, cryotherapy causes cell death and tissue necrosis or tissue adherence that can be used via the flexible or rigid bronchoscope. This extreme cold can be used through the working channel of the bronchoscope via a specialized cryoprobe or directly with the use of spray cryotherapy. These properties allow for multiple bronchoscopic techniques, each with its own equipment and procedural, safety, and efficacy considerations. Bronchoscopic cryotherapy can be used in a variety of clinical scenarios, including the treatment of malignant and benign central airway obstruction and low-grade airway malignancy, foreign body removal or cryoextraction, endobronchial biopsy, and transbronchial biopsy. The bulk of the experience with bronchoscopic cryotherapy consists of uncontrolled case series of malignant central airway obstruction. There are also controlled data supporting the use of cryoadhesion for endobronchial biopsies, albeit with an increased risk of controllable bleeding. The use of cryoadhesion for transbronchial biopsies is an active area of investigation with limited controlled data. In addition, there are promising future directions using bronchoscopic cryotherapy, including chemosensitizing malignancy with cryotherapy and capitalizing on the synergy between cryotherapy and radiation.

Background Next-generation sequencing is available for assessing genomic alterations in non–small-cell lung cancer (NSCLC), although the performance characteristics and clinical utility has not been well characterized. This technique can be used to sequence hundreds of known cancer-associated genes. Our aim was to investigate the diagnostic success and clinically relevant results of extensive sequencing in NSCLC patients. Patients and Methods A case series of 49 NSCLC patients was used to determine the success of extended next-generation sequencing, record genomic alterations, and evaluate clinical utility. Data were collected in a retrospective review. Sequencing was performed using a hybridization capture of 3320 exons from 236 cancer-related genes and 47 introns of 19 genes applied to ≥50 ng of DNA and sequenced to high, uniform coverage of 622 times. Results Sequencing was successful in 29 of 32 (91%) surgical/excisional specimens, and 12 of 17 (71%) nonsurgical specimens including an endoscopic forceps biopsy, core needle biopsies, fine-needle aspirates, and effusion cytologies. All 5 transthoracic core needle biopsies failed. A total of 179 genomic alterations (average 4.37 per tumor) were found. A total of 63 were clinically relevant (average 1.54 per tumor). The most frequently mutated genes were tumor protein p53, cyclin-dependent kinase inhibitor 2A, megalencephalic leukoencephalopathy with subcortical cysts 1, rapamycin-insensitive companion of mammalian target of rapamycin, epithelial growth factor receptor, SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 4, cyclin-dependent kinase inhibitor 2B, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α, Kirsten rat sarcoma viral oncogene homolog, Erb-B2 receptor tyrosine kinase 2, Serine/Threonine Kinase 11, and NK2 Homeobox 1. Sequencing results led to a change in management in 7 of 49 cases (14.3%). Conclusion Extended next-generation sequencing was performed successfully in 41 (83.7%) cases of NSCLC using a range of pathology specimens. Testing had the potential to affect treatment decisions in selected patients.

Background: Next-generation sequencing (NGS) with a multi-gene panel is now available for patients with lung adenocarcinoma, but the performance characteristics and clinical utility of this testing are not well-described. We present the results of an extended 467 gene panel in a series of advanced, highly selected nonsmall cell lung cancer (NSCLC) patients using a range of specimens, including predominantly small biopsy and cytology specimens. Materials and Methods: A retrospective review of 22 NSCLC biopsies sent for NGS using an extended gene panel from January 2014 to July 2015. The customized NGS panel sequences 467 cancer-associated genes with exonic and intronic sequences obtained from purified tumor DNA. Genomic alterations, patient characteristics, and success of testing were determined. Results: The majority of samples tested were metastatic lung adenocarcinoma on final pathology. Of the 22 specimens tested, 5 (22.7%) were surgical resections and 17 (77.3%) were small biopsy and cytology specimens. Twenty-one (95%) of the specimens were adequate for full sequencing and yielded a total of 204 genomic alterations (average 8.9 per tumor), of which 17 (average 0.81 per tumor) were actionable and/or clinically relevant. Genomic alterations were found most commonly in the TP53, EGFR, EPHB1, MLL3, APC, SETD2, KRAS, DNMT3A, RB1, CDKN2A, ARID1A, EP300, KDM6B, RAD50, STK11, and BRCA2 genes. Conclusions: NGS using a comprehensive gene panel was performed successfully in 95% of all NSCLC cases in this series, including 94% small biopsy and cytology specimens and 100% surgical resections. This custom assay was performed on a range of tumor specimens and demonstrates that small specimens are able to provide a similar depth of information as larger ones. As many patients present at an advanced stage and only small specimens are obtained, the information these provide has the potential for guiding treatment in highly selected patients with advanced lung adenocarcinoma.