Electromagnetic Navigation Transthoracic Nodule Localization for Minimally Invasive Thoracic Surgery.

The increased use of chest computed tomography (CT) has led to an increased detection of pulmonary nodules requiring diagnostic evaluation and/or excision. Many of these nodules are identified and excised via minimally invasive thoracic surgery; however, subcentimeter and subsolid nodules are frequently difficult to identify intra-operatively. This can be mitigated by the use of electromagnetic transthoracic needle localization. This protocol delineates the step-by-step process of electromagnetic localization from the pre-operative period to the postoperative period and is an adaptation of the electromagnetically guided percutaneous biopsy previously described by Arias et al. Pre-operative steps include obtaining a same day CT followed by the generation of a three-dimensional virtual map of the lung. From this map, the target lesion(s) and an entry site are chosen. In the operating room, the virtual reconstruction of the lung is then calibrated with the patient and the electromagnetic navigation platform. The patient is then sedated, intubated, and placed in the lateral decubitus position. Using a sterile technique and visualization from multiple views, the needle is inserted into the chest wall at the prechosen skin entry site and driven down to the target lesion. Dye is then injected into the lesion and, then, continuously during needle withdrawal, creating a tract for visualization intra-operatively. This method has many potential benefits when compared to the CT-guided localization, including a decreased radiation exposure and decreased time between the dye injection and the surgery. Dye diffusion from the pathway occurs over time, thereby limiting intra-operative nodule identification. By decreasing the time to surgery, there is a decrease in wait time for the patient, and less time for dye diffusion to occur, resulting in an improvement in nodule localization. When compared to electromagnetic bronchoscopy, airway architecture is no longer a limitation as the target nodule is accessed via a transparenchymal approach. Details of this procedure are described in a step-by-step fashion.

A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking.

Lung squamous carcinoma (LUSC) is a highly metastatic disease with a poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of circRNA is through miRNA sponging, we found that miR-671-5p more potently silenced an axis of CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing of CDR1as or CDR1 significantly inhibited LUSC metastases and CDR1 was sufficient to promote migration and metastases. CDR1, which directly interacted with adaptor protein 1 (AP1) complex subunits and coatomer protein I (COPI) proteins, no longer promoted migration upon blockade of Golgi trafficking. Therapeutic inhibition of the CDR1as/CDR1 axis with miR-671-5p mimics reduced metastasis in vivo. This report demonstrates a novel role for CDR1 in promoting metastasis and Golgi trafficking. These findings reveal an miRNA/circRNA axis that regulates LUSC metastases through a previously unstudied protein, CDR1. SIGNIFICANCE: This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1.

AABIP Evidence-informed Guidelines and Expert Panel Report for the Management of Indwelling Pleural Catheters.

BACKGROUND: While the efficacy of Indwelling pleural catheters for palliation of malignant pleural effusions is supported by relatively robust evidence, there is less clarity surrounding the postinsertion management. METHODS: The Trustworthy Consensus-Based Statement approach was utilized to develop unbiased, scientifically valid guidance for the management of patients with malignant effusions treated with indwelling pleural catheters. A comprehensive electronic database search of PubMed was performed based on a priori crafted PICO questions (Population/Intervention/Comparator/Outcomes paradigm). Manual searches of the literature were performed to identify additional relevant literature. Dual screenings at the title, abstract, and full-text levels were performed. Identified studies were then assessed for quality based on a combination of validated tools. Appropriateness for data pooling and formation of evidence-based recommendations was assessed using predetermined criteria. All panel members participated in development of the final recommendations utilizing the modified Delphi technique. RESULTS: A total of 7 studies were identified for formal quality assessment, all of which were deemed to have a high risk of bias. There was insufficient evidence to allow for data pooling and formation of any evidence-based recommendations. Panel consensus resulted in 11 ungraded consensus-based recommendations. CONCLUSION: This manuscript was developed to provide clinicians with guidance on the management of patients with indwelling pleural catheters placed for palliation of malignant pleural effusions. Through a systematic and rigorous process, management suggestions were developed based on the best available evidence with augmentation by expert opinion when necessary. In addition, these guidelines highlight important gaps in knowledge which require further study.

Incidence and clinical relevance of non-small cell lung cancer lymph node micro-metastasis detected by staging endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: Approximately twenty percent of lymph node (LN) negative non-small cell lung cancer (NSCLC) patients who undergo curative intent surgery have pan-cytokeratin immunohistochemistry (IHC)-detectable occult micro-metastases (MMs) in resected LNs. The presence of the MMs in NSCLC is associated worsened outcomes. As a substantial proportion of NSCLC LN staging is conducted using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), we sought to determine the frequency of detection of occult MMs in EBUS-TBNA specimens and to evaluate the impact of MMs on progression-free and overall survival. METHODS: We performed retrospective IHC staining for pan-cytokeratin of EBUS-TBNA specimens previously deemed negative by a cytopathologist based on conventional hematoxylin and eosin staining. The results were correlated with clinical variables, including survival outcomes. RESULTS: Of 887 patients screened, 44 patients were identified meeting inclusion criteria with sufficient additional tissue for testing. With respect to the time of the EBUS-TBNA procedure, 52% of patients were clinical stage I, 34% clinical stage II, and clinical 14% stage IIIa NSCLC. Three patients (6.8%) were found to have cytokeratin positive MMs. All 3 MMs detected were at N2 LN stations. The presence of MMs was associated with significantly decreased progression-free (median 210 vs. 1,293 days, P=0.0093) and overall survival (median 239 vs. 1,120 days, P=0.0357). CONCLUSIONS: Occult LN MMs can be detected in EBUS-TBNA specimens obtained during staging examinations and are associated with poor clinical outcomes. If prospectively confirmed, these results have significant implications for EBUS-TBNA specimen analyses and possibly for the NSCLC staging paradigm.

Peripheral Lung Nodule Diagnosis and Fiducial Marker Placement Using a Novel Tip-Tracked Electromagnetic Navigation Bronchoscopy System.

BACKGROUND: Electromagnetic navigation (EMN) has improved bronchoscopic access to peripheral pulmonary nodules. A novel EMN system utilizing novel tip-tracked instruments for endobronchial [electromagnetic navigation bronchoscopy (ENB)] as well as transthoracic lung biopsy [electromagnetic-guided transthoracic needle aspiration (EMTTNA)] has become available. The system provides real-time feedback as well as the ability to biopsy lesions outside of the airway. These advances have the potential to improve diagnostic yield over previous EMN systems. METHODS: We performed a retrospective review of consecutive peripheral bronchoscopy cases utilizing a novel EMN platform for biopsy and/or fiducial marker (FM) placement at a tertiary care university hospital. We analyzed factors that may influence diagnostic yield including lesion size. RESULTS: Our study included 108 patients who underwent EMN-guided bronchoscopy between June 2015 and April 2017 for the diagnosis of peripheral lung lesions and/or the placement of FMs for stereotactic body radiotherapy. Ninety-three patients underwent biopsy utilizing ENB +/- EMTTNA. The combined diagnostic yield was 78%. EMTTNA provided a diagnosis for 5 patients in whom the ENB biopsy results were negative. Diagnostic yield by nodules <20, 20 to 30, and >30 mm in size was 30/45 (67%), 27/30 (90%), and 16/18 (89%), respectively. Sixty-five patients underwent FM placement with a total of 133 FM placed. CONCLUSION: This novel tip-tracked EMN system incorporating both ENB and EMTTNA can guide biopsy and FM placement with a high degree of success and with a low complication rate. Multicentered prospective trials are required to develop algorithmic approaches to combine ENB and EMTTNA into a single procedure.

An update on the role of advanced diagnostic bronchoscopy in the evaluation and staging of lung cancer.

Lung cancer remains a common and deadly disease. Many modalities are available to the bronchoscopist to evaluate and stage lung cancer. We review the role of bronchoscopy in the staging of the mediastinum with convex endobronchial ultrasound (EBUS) and discuss emerging role of esophageal ultrasonography as a complementary modality. In addition, we discuss advances in scope technology and elastography. We review the bronchoscopic methods available for the diagnosis of peripheral lung nodules including radial EBUS and navigational bronchoscopy (NB) with a consideration of the basic methodologies and diagnostic accuracies. We conclude with a discussion of the comparison of the various methodologies.

Pleural effusions in non-transplanted cystic fibrosis patients.

BACKGROUND: Pleural effusions are considered rare in cystic fibrosis (CF) patients. There is a paucity of available information in the literature concerning the nature and significance of pleural effusions in non-transplanted CF patients. METHODS: We conducted a multicenter retrospective evaluation of non-transplanted adult CF patients. Given the small sample size, only descriptive statistics were performed. RESULTS: A total of 17 CF patients with pleural effusion were identified, of whom 9 patients underwent thoracentesis. The crude incidence of pleural effusion was 43 per 10,000 person-years in hospitalized CF patients at large CF centers. All sampled effusions were inflammatory in nature. All samples submitted for culture grew at least one organism. CONCLUSION: Pleural effusions are rare in adult non-transplanted CF patients. These fluid collections appear to be quite inflammatory with a higher rate of empyema than in the general population.

Convex Endobronchial Ultrasound-Guided Fiducial Placement for Malignant Central Lung Lesions: A Case Series.

BACKGROUND: Stereotactic radiotherapy is a useful therapeutic modality in patients with lung cancer and patients with pulmonary metastases who cannot tolerate, are not candidates for, or do not want surgery. Successful use of radial endobronchial ultrasound (EBUS) and navigation bronchoscopy to guide the placement of the fiducials required for stereotactic radiotherapy in peripheral lung lesions has been previously reported. We present the first series of patients in which convex-probe EBUS was used to deliver fiducials to hilar and mediastinal lymph nodes as well as central thoracic lesions. METHODS: Retrospective case series of 5 patients in which convex-probe EBUS was used to place fiducials in central lesions. RESULTS: Fiducial markers were successfully placed in all 5 patients and were durable. There were no procedure-related complications. CONCLUSION: Convex-probe EBUS is a useful tool in the placement of fiducial markers in patients with malignant lymphadenopathy and central parenchymal lung lesions.

Intra-arterial methylprednisolone infusion in treatment-resistant graft-versus-host disease.

Acute graft-versus-host disease (GVHD) is a potentially fatal complication following allogeneic hematopoietic stem cell transplant. Standard primary therapy for acute GVHD includes systemic steroids, often in combination with other agents. Unfortunately, primary treatment failure is common and carries a high mortality. There is no generally accepted secondary therapy for acute GVHD. Although few data on localized therapy for GVHD have been published, intra-arterial injection of high-dose corticosteroids may be a viable option. We treated 11 patients with steroid-resistant GVHD using a single administration of intra-arterial high-dose methylprednisolone. Three patients (27%) died periprocedurally. Four patients (36%) had a partial response to intra-arterial treatment and were discharged on total parenteral nutrition and oral medication. Four patients (36%) had a complete response and were discharged on oral diet and oral medication. No immediate treatment or procedure-related complications were noted. Twenty-seven percent of patients survived long-term. Our preliminary results suggest that regional intra-arterial treatment of steroid-resistant GVHD is a safe and potentially viable secondary therapy in primary treatment-resistant GVHD.

New classification scheme of left ventricular noncompaction and correlation with ventricular performance.

Isolated left ventricular noncompaction (LVNC) is an increasingly-recognized cardiomyopathy, and the possibility that it exists as a spectrum of disease has yet to be explored. We sought to determine the prevalence, spectrum, and functional consequences of LVNC; 2 blinded reviewers assessed 500 transthoracic echocardiograms for LVNC for adequate study quality, absence of co-existing cardiomyopathy, and LVNC. If present, the ratio of the maximum linear length of noncompacted to compacted myocardium (NC/C) and the planimetered area of LVNC on apical 4-chamber view were measured. Patients were classified by degree of noncompaction measured by either the NC/C ratio or LVNC area as controls, mild, moderate, and severe; 380 patients were included in the analysis and 60 (15.8%) had evidence of noncompaction. Patients with increasing severity of noncompaction had significantly decreased ejection fractions. In conclusion, these findings indicate that LVNC may be more common than previously recognized and may exist as a spectrum, which can be classified using the NC/C ratio or LVNC area classification schemes.

Prevalence of metabolic syndrome in retired National Football League players.

The National Institute of Occupational Safety and Health mortality study of National Football League (NFL) players concluded that retired NFL linemen have an increased risk of cardiovascular death compared with both nonlinemen and the general population. Though elevated body mass index contributed to the increased cardiac risk of linemen, it could not fully account for the mortality observed, suggesting that other unmeasured cardiovascular risk factors were involved. We performed a cross-sectional prevalence study of metabolic syndrome (MS), and its individual component criteria, in 510 retired NFL players who were recruited to multicity health screenings from February 2004 through June 2006. The International Diabetes Federation criteria were used to define MS. The MS component criteria of body mass index>30 kg/m2, reduced high-density lipoprotein, and raised fasting glucose were more prevalent in linemen compared with nonlinemen (85.4% vs 50.3%, p<0.001; 42.1% vs 32.7%, p=0.04; 60.4% vs 37.6%, p<0.001, respectively). Metabolic syndrome was more prevalent in linemen compared with nonlinemen (59.8% vs 30.1%, p<0.001). In conclusion, linemen exhibited a high prevalence of MS, almost double the prevalence of their nonlinemen counterparts. These findings may partially explain the increased risk for cardiovascular death observed in retired linemen and could have significant public health implications for preprofessional training regimens and postprofessional health maintenance.