Robot-Assisted Bronchoscopy for Identification of Lung Nodules During Minimally Invasive Pulmonary Resection.

OBJECTIVE: Small pulmonary nodules can be difficult to identify during minimally invasive surgical (MIS) resection. Previous investigators have reported using standard bronchoscopy with electromagnetic navigation to identify small pulmonary nodules. Robot-assisted bronchoscopy has been introduced into clinical practice and has shown utility for the biopsy of small lesions. We report our experience using robot-assisted bronchoscopy with dye marking to aid in minimally invasive pulmonary resection. METHODS: Patients with peripheral pulmonary nodules underwent robot-assisted bronchoscopy before a planned minimally invasive resection. Indocyanine green or methylene blue was injected directly into the targeted lesion. Surgical resection was then immediately performed. Success was defined as dye visualization leading to sublobar resection of the target nodule without the need for lobectomy or thoracotomy. RESULTS: Thirty patients with a single targeted nodule underwent robot-assisted bronchoscopy followed by MIS resection. The median lesion size was 9 mm (4 to 25 mm), and the median distance from the pleura was 5 mm (1 to 32 mm). The success rate was 83.3% (25 of 30). There were 3 cases in which the dye was not visualized, and in 2 cases there was free extravasation of dye. The targeted nodule was identified in these 5 patients without the need for thoracotomy or lobectomy. Pathology revealed non-small cell lung cancer (n = 13, 43.3%), metastatic disease (n = 11, 36.7%), and benign disease (n = 6, 20%). There were no complications related to the use of robot-assisted bronchoscopy. CONCLUSIONS: Robot-assisted bronchoscopy with dye marking is safe and effective for guiding minimally invasive resection of small peripheral pulmonary nodules.

Navigating a Career in Medicine as a Woman.

Despite the increasing number of women within medical professions, gender equality in career advancement and leadership positions still remains a challenge due to numerous barriers including unbalanced domestic responsibilities, discrimination, and rigidity in career structures. Here, we discuss ways to achieve work-life balance and family planning as well as some of the challenges women face in medicine and nursing careers and outline strategies for individuals and organizations to overcome them.

Pleural Fluid Resolution Is Associated with Improved Survival in Patients with Malignant Pleural Effusion.

Malignant pleural effusion is associated with a poor prognosis and, while risk stratification models exist, prior studies have not evaluated pleural fluid resolution and its association with survival. We performed a retrospective review of patients diagnosed with malignant pleural effusion between 2013 and 2017, evaluating patient demographics, pleural fluid and serum composition, and procedural and treatment data using Cox regression analysis to evaluate associations with survival. In total, 123 patients were included in the study, with median survival from diagnosis being 4.8 months. Resolution of malignant pleural fluid was associated with a significant survival benefit, even when accounting for factors such as placement of an indwelling pleural catheter, anti-cancer therapy, pleural fluid cytology, cancer pheno/genotypes, and pleural fluid characteristics. Elevated fluid protein, placement of an indwelling pleural catheter, and treatment with targeted or hormone therapies were associated with pleural fluid resolution. We conclude that the resolution of pleural fluid accumulation in patients with malignant pleural effusion is associated with a survival benefit possibility representing a surrogate marker for treatment of the underlying metastatic cancer. These findings support the need to better understand the mechanism of fluid resolution in patients with malignant pleural effusion as well as the tumor-immune interplay occurring with the malignant pleural space.

A maladaptive pleural environment suppresses preexisting anti-tumor activity of pleural infiltrating T cells.

Introduction: Treatment options for patients with malignant pleural effusions (MPE) are limited due, at least in part, to the unique environment of the pleural space, which drives an aggressive tumor state and governs the behavior of infiltrating immune cells. Modulation of the pleural environment may be a necessary step toward the development of effective treatments. We examine immune checkpoint molecule (ICM) expression on pleural T cells, the secretomes of pleural fluid, pleural infiltrating T cells (PIT), and ability to activate PIT ex vivo. Methods: ICM expression was determined on freshly drained and in vitro activated PIT from breast, lung and renal cell cancer. Secretomics (63 analytes) of activated PIT, primary tumor cultures and MPE fluid was determined using Luminex technology. Complementary digital spatial proteomic profiling (42 analytes) of CD45+ MPE cells was done using the Nanostring GeoMx platform. Cytolytic activity was measured against autologous tumor targets. Results: ICM expression was low on freshy isolated PIT; regulatory T cells (T-reg) were not detectable by GeoMx. In vitro activated PIT coexpressed PD-1, LAG-3 and TIGIT but were highly cytotoxic against autologous tumor and uniquely secreted cytokines and chemokines in the > 100 pM range. These included CCL4, CCL3, granzyme B, IL-13, TNFα, IL-2 IFNγ, GM-CSF, and perforin. Activated PIT also secreted high levels of IL-6, IL-8 and sIL-6Rα, which contribute to polarization of the pleural environment toward wound healing and the epithelial to mesenchymal transition. Addition of IL-6Rα antagonist to cultures reversed tumor EMT but did not alter PIT activation, cytokine secretion or cytotoxicity. Discussion: Despite the negative environment, immune effector cells are plentiful, persist in MPE in a quiescent state, and are easily activated and expanded in culture. Low expression of ICM on native PIT may explain reported lack of responsiveness to immune checkpoint blockade. The potent cytotoxic activity of activated PIT and a proof-of-concept clinical scale GMP-expansion experiment support their promise as a cellular therapeutic. We expect that a successful approach will require combining cellular therapy with pleural conditioning using immune checkpoint blockers together with inhibitors of upstream master cytokines such as the IL-6/IL-6R axis.

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.

Feasibility of a prototype carbon nanotube enabled stationary digital chest tomosynthesis system for identification of pulmonary nodules by pulmonologists.

Background: Screen detected and incidental pulmonary nodules are increasingly common. Current guidelines recommend tissue sampling of solid nodules >8 mm. Bronchoscopic biopsy poses the lowest risk but is paired with the lowest diagnostic yield when compared to CT-guided biopsy or surgery. A need exists for a safe, mobile, low radiation dose, intra-procedural method to localize biopsy instruments within target nodules. This retrospective cross sectional reader feasibility study evaluates the ability of clinicians to identify pulmonary nodules using a prototype carbon nanotube radiation enabled stationary digital chest tomosynthesis system. Methods: Patients with pulmonary nodules on prior CT imaging were recruited and consented for imaging with stationary digital chest tomosynthesis. Five pulmonologists of varying training levels participated as readers. Following review of patient CT and a thoracic radiologist's interpretation of nodule size and location the readers were tasked with interpreting the corresponding tomosynthesis scan to identify the same nodule found on CT. Results: Fifty-five patients were scanned with stationary digital chest tomosynthesis. The median nodule size was 6 mm (IQR =4-13 mm). Twenty nodules (37%) were greater than 8 mm. The radiation entrance dose for s-DCT was 0.6 mGy. A significant difference in identification of nodules using s-DCT was seen for nodules <8 vs. ≥8 mm in size (57.7% vs. 90.9%, CI: -0.375, -0.024; P<0.001). Inter-reader agreement was fair, and better for nodules ≥8 mm [0.278 (SE =0.043)]. Conclusions: With system and carbon nanotube array optimization, we hypothesize the detection rate for nodules will improve. Additional study is needed to evaluate its use in target and tool co-localization and target biopsy.

Case of a 57-Year-Old Man With Malignant Mesothelioma Presenting With Miliary Nodules on Chest Imaging.

CASE PRESENTATION: A 57-year-old man with history of stage IIIB right-sided malignant pleural mesothelioma was admitted from his oncologist's office for progressive dyspnea of two weeks duration. He had associated dyspnea at rest and a new dry cough. He denied sputum production, hemoptysis, or fevers, but he did endorse chills, fatigue, and weight loss. The patient was a veteran of the Navy and had extensive international travel in his 20s. He had never been incarcerated and denied any sick contacts or recent travels. He had received a diagnosis of mesothelioma 11 months earlier after presenting to his physician's office with complaints of shortness of breath on exertion. Initial imaging revealed a large right-sided pleural effusion with irregular pleural thickening. He underwent right-sided thoracoscopy, and the pleural biopsy result was consistent with epithelioid mesothelioma. Because of invasion of his seventh rib, he was not a candidate for surgery and underwent palliative radiation and chemotherapy with cisplatin, pemetrexed, and bevacizumab. He was undergoing his eighth cycle of chemotherapy at the time of presentation.

Atypical Mycobacterium Abscessus Infection in Stable Chronic Lymphocytic Leukemia: A Case Report and Review of the Literature.

Chronic lymphocytic leukemia is the most common blood cancer in adults. A major cause of morbidity and mortality associated with this cancer stems from opportunistic infections. Similar to many cancers, the inherent effects of battling a raging disease along with the many treatment options causing immunosuppression to lend to the likelihood of obtaining secondary infections. As it is important for physicians to note the ever-increasing secondary complications, which can manifest in the long-term management of immunosuppressed patients, we present a case of an 86-year-old Caucasian female with stable chronic lymphocytic leukemia who developed intermittent presentation of lung abscesses due to growth of atypical Mycobacterium species. With the advent of new treatment options, there has been an increased rate of drug-resistant organisms, lending for the need for more awareness to the severity of these secondary complications and for better options in preventing their occurrence.

Surgical Interventions for COPD.

Chronic obstructive pulmonary disease (COPD) treatment is aimed at managing the disease rather than cure, with a focus on improving quality of life and decreasing exacerbations. Interventional therapies, including lung volume reduction surgery, bullectomy, lung transplantation, and bronchoscopic lung volume reduction treatment using endobronchial valves, are treatment options for patients with COPD who are symptomatic due to hyperinflation despite optimal medical management. We will review the current literature to provide a comprehensive summary of the currently available scientific data, discuss typical treatment-related side effects, and evidence-based management approach and recommendations for patient selection in clinical practice.

Electromagnetic Transthoracic Nodule Localization for Minimally Invasive Pulmonary Resection.

BACKGROUND: Increased use of chest computed tomography and the institution of lung cancer screening have increased the detection of ground-glass and small pulmonary nodules. Intraoperative localization of these lesions via a minimally invasive thoracoscopic approach can be challenging. We present the feasibility of perioperative transthoracic percutaneous nodule localization using a novel electromagnetic navigation platform. METHODS: This is a multicenter retrospective analysis of a prospectively collected database of patients who underwent perioperative electromagnetic transthoracic nodule localization before attempted minimally invasive resection between July 2016 and March 2018. Localization was performed using methylene blue or a mixture of methylene blue and the patient's blood (1:1 ratio). Patient, nodule, and procedure characteristics were collected and reported. RESULTS: Thirty-one nodules were resected from 30 patients. Twenty-nine of 31 nodules (94%) were successfully localized. Minimally invasive resection was successful in 93% of patients (28/30); 7% (2/30) required conversion to thoracotomy. The median nodule size was 13 mm (interquartile range 25%-75%, 9.5-15.5), and the median depth from the surface of the visceral pleura to the nodule was 10 mm (interquartile range 25%-75%, 5.0-15.9). Seventy-one percent (22/31) of nodules were malignant. No complications associated with nodule localization were reported. CONCLUSIONS: The use of intraoperative electromagnetic transthoracic nodule localization before thoracoscopic resection of small and/or difficult to palpate lung nodules is safe and effective, potentially eliminating the need for direct nodule palpation. Use of this technique aids in minimally invasive localization and resection of small, deep, and/or ground-glass lung nodules.

Prevalence and factors associated with suboptimal peak inspiratory flow rates in COPD.

PURPOSE: Adequate peak inspiratory flow rate (PIFR) is required for drug dispersion with dry powder inhalers (DPIs). Prevalence of PIFR discordance (suboptimal PIFR with prescribed inhalers) and factors influencing device-specific PIFR are unclear in COPD. The objective of this study was to determine the prevalence of PIFR discordance and associated clinical factors in a stable COPD population. PATIENTS AND METHODS: An observational, single-center, cohort study was conducted including 66 outpatients with COPD. PIFR was measured using the In-Check™ Dial with applied resistance of prescribed inhalers. Participants were defined as discordant if measured PIFR was <30 L/min and <60 L/min for high and low-medium resistance devices, respectively, using an inspiratory effort the participant normally used with their prescribed DPI. RESULTS: The median age of the COPD participants was 69.4 years, 92% were white and 47% were female. A total of 48% were using low-medium resistance DPIs (Diskus®/Ellipta®) and 76% used high-resistance DPI (Handihaler®). A total of 40% of COPD participants were discordant to prescribed inhalers. Female gender was the only factor consistently associated with lower PIFR. Shorter height was associated with reduced PIFR for low-medium resistance (r=0.44; P=0.01), but not high resistance (r=0.20; P=0.16). There was no correlation between PIFR by In-Check™ dial and PIFR measured by standard spirometer. CONCLUSION: PIFR is reduced in stable COPD patients, with female gender being the only factor consistently associated with reduced PIFR. Discordance with prescribed inhalers was seen in 40% of COPD patients, suggesting that many COPD patients do not generate adequate inspiratory force to overcome prescribed DPIs resistance in the course of normal use.

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.

Alignment of Inhaled Chronic Obstructive Pulmonary Disease Therapies with Published Strategies. Analysis of the Global Initiative for Chronic Obstructive Lung Disease Recommendations in SPIROMICS.

RATIONALE: Despite awareness of chronic obstructive pulmonary disease (COPD) treatment recommendations, uptake is poor. The Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) spans 2010-2016, providing an opportunity to assess integration of 2011 Global Initiative for Obstructive Lung Disease (GOLD) treatment strategies over time in a large observational cohort study. OBJECTIVES: To evaluate how COPD treatment aligns with 2011 GOLD strategies and determine factors associated with failure to align with recommendations. METHODS: Information on inhaled medication use collected via questionnaire annually for 4 years was compiled into therapeutic classes (long-acting antimuscarinic agent, long-acting ß-agonist, inhaled corticosteroids [ICS], and combinations thereof). Medications were not modified by SPIROMICS investigators. 2011 GOLD COPD categories A, B, C, and D were assigned. Alignment of inhaler regimen with first-/second-line GOLD recommendations was determined, stratifying into recommendation aligned or nonaligned. Recommendation-nonaligned participants were further stratified into overuse and underuse categories. RESULTS: Of 1,721 participants with COPD, at baseline, 52% of regimens aligned with GOLD recommendations. Among participants with nonaligned regimens, 46% reported underuse, predominately owing to lack of long-acting inhalers in GOLD category D. Of the 54% reporting overuse, 95% were treated with nonindicated ICS-containing regimens. Among 431 participants with 4 years of follow-up data, recommendation alignment did not change over time. When we compared 2011 and 2017 recommendations, we found that 47% did not align with either set of recommendations, whereas 35% were in alignment with both recommendations. CONCLUSIONS: Among SPIROMICS participants with COPD, nearly 50% reported inhaler regimens that did not align with GOLD recommendations. Nonalignment was driven largely by overuse of ICS regimens in milder disease and lack of long-acting inhalers in severe disease.

Peak Inspiratory Flow Rate in Chronic Obstructive Pulmonary Disease: Implications for Dry Powder Inhalers.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with a significant economic burden related to hospital admissions for exacerbations. One of the primary treatment modalities for COPD is medications delivered through breath-actuated dry powdered inhalers (DPIs). For users to successfully receive inhaled medication, they must inhale with enough flow to overcome the internal resistance of the device, leading to deaggregation of the medication powder. Peak inspiratory flow rate (PIFR) is the maximal flow rate obtained during an inspiratory maneuver. PIFR measurement can be impacted by the internal resistance of the device, which varies with device design. Many devices require a PIFR >60 L/min for adequate medication dispersal, while others appear to have adequate drug deaggregation with a PIFR >30 L/min. Studies have shown PIFRs are reduced among females and decrease with age, without a clear correlation between forced expiratory volume in 1 second and PIFR. PIFR can be reduced at the time of COPD exacerbation. Recent data suggest that reduced PIFR may be associated with worse COPD-related symptom burden, increased odds of COPD-related hospital readmissions, and improved responsiveness to nebulized therapy. This review article aims to examine the physiology and clinical correlations of PIFR, as well as review published studies related to PIFR with DPIs used to treat COPD.

Electronic cigarettes as smoking cessation tool: are we there?

PURPOSE OF REVIEW: Electronic cigarette (e-cigarette) use is rapidly increasing, with many users reporting trying e-cigarettes as a method to quit combustible cigarettes. This review highlights recently published studies assessing the use of e-cigarettes as a tool for cessation of combustible cigarettes. RECENT FINDINGS: When evaluating data from four randomized controlled trials and multiple cohort studies, differential association between e-cigarette use and cessation rates was seen. Cessation rates are highest in UK cohort studies and in studies using a multifaceted approach, such as with the addition of varenicline. The largest evidence base is derived from observational cohort studies. Overall, the current evidence remains too small for conclusive results regarding efficacy of e-cigarettes for combustible cessation. There does appear to be a consistent reduction in daily combustible cigarette use in regular e-cigarette users. SUMMARY: Currently, there are conflicting data which can be used to support or dismiss e-cigarettes as a tool for smoking cessation. As larger population-based studies become available, the potential harms and benefits of e-cigarettes will become clearer. In the short term, shared decision-making with combustible cigarette users will be imperative when considering e-cigarettes as a smoking cessation tool.