Safety and utility of indwelling pleural catheters in lung transplant recipients.

INTRODUCTION: The safety and efficacy of indwelling pleural catheters (IPCs) in lung allograft recipients is under-reported. METHODS: We performed a multicenter, retrospective analysis between 1/1/2010 and 6/1/2022 of consecutive IPCs placed in lung transplant recipients. Outcomes included incidence of infectious and non-infectious complications and rate of auto-pleurodesis. RESULTS: Seventy-one IPCs placed in 61 lung transplant patients at eight centers were included. The most common indication for IPC placement was recurrent post-operative effusion. IPCs were placed at a median of 59 days (IQR 40-203) post-transplant and remained for 43 days (IQR 25-88). There was a total of eight (11%) complications. Infection occurred in five patients (7%); four had empyema and one had a catheter tract infection. IPCs did not cause death or critical illness in our cohort. Auto-pleurodesis leading to the removal of the IPC occurred in 63 (89%) instances. None of the patients in this cohort required subsequent surgical decortication. CONCLUSIONS: The use of IPCs in lung transplant patients was associated with an infectious complication rate comparable to other populations previously studied. A high rate of auto-pleurodesis was observed. This work suggests that IPCs may be considered for the management of recurrent pleural effusions in lung allograft recipients.

Sight Unseen: Diagnostic Yield and Safety Outcomes of a Novel Multimodality Navigation Bronchoscopy Platform with Real-Time Target Acquisition.

BACKGROUND: Several advanced bronchoscopy platforms are currently available, but the clinical data supporting their use vary. Electromagnetic navigation bronchoscopy (ENB) remains the dominant technology; it is limited by its reliance on preoperative computed tomography, which only approximates patient anatomy during the procedure. Recently, ENB was enhanced with the (1) addition of digital tomosynthesis-based navigation correction, (2) improvements in planning algorithms, and (3) continuous real-time guidance (Illumisite™; Medtronic, Minneapolis, MN, USA). There are currently no clinical data on the diagnostic yield and safety profile of this system. OBJECTIVES: The primary objective of this study is to describe the diagnostic yield of the first 100 pulmonary parenchymal lesions sampled using the multimodality navigation bronchoscopy (MNB) platform. The secondary objective is to describe safety. METHODS: In this single-center prospective observational study, a database was maintained to track patient, procedural, and outcome data for the first 100 consecutive lesions sampled using the MNB platform at an academic quaternary referral center. Descriptive statistics and univariate and multivariate analyses are reported. RESULTS: The overall diagnostic yield of samples acquired was 79% (79/100). In the cohort where digital tomosynthesis was used, the diagnostic yield was 83% (69/83). Sensitivity for malignancy was 71% (52/73). Overall complication rates were low: pneumothorax (n = 3, 3%) and bleeding requiring intervention (n = 2, 2%). There were no procedural-related hospital admissions. CONCLUSIONS: The MNB system performed favorably. Platform superiority cannot be established without future prospective and comparative studies.

Extensive phenotyping of individuals at risk for familial interstitial pneumonia reveals clues to the pathogenesis of interstitial lung disease.

RATIONALE: Asymptomatic relatives of patients with familial interstitial pneumonia (FIP), the inherited form of idiopathic interstitial pneumonia, carry increased risk for developing interstitial lung disease. OBJECTIVES: Studying these at-risk individuals provides a unique opportunity to investigate early stages of FIP pathogenesis and develop predictive models of disease onset. METHODS: Seventy-five asymptomatic first-degree relatives of FIP patients (mean age, 50.8 yr) underwent blood sampling and high-resolution chest computed tomography (HRCT) scanning in an ongoing cohort study; 72 consented to bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies. Twenty-seven healthy individuals were used as control subjects. MEASUREMENTS AND MAIN RESULTS: Eleven of 75 at-risk subjects (14%) had evidence of interstitial changes by HRCT, whereas 35.2% had abnormalities on transbronchial biopsies. No differences were noted in inflammatory cells in BAL between at-risk individuals and control subjects. At-risk subjects had increased herpesvirus DNA in cell-free BAL and evidence of herpesvirus antigen expression in alveolar epithelial cells (AECs), which correlated with expression of endoplasmic reticulum stress markers in AECs. Peripheral blood mononuclear cell and AEC telomere length were shorter in at-risk individuals than healthy control subjects. The minor allele frequency of the Muc5B rs35705950 promoter polymorphism was increased in at-risk subjects. Levels of several plasma biomarkers differed between at-risk subjects and control subjects, and correlated with abnormal HRCT scans. CONCLUSIONS: Evidence of lung parenchymal remodeling and epithelial dysfunction was identified in asymptomatic individuals at risk for FIP. Together, these findings offer new insights into the early pathogenesis of idiopathic interstitial pneumonia and provide an ongoing opportunity to characterize presymptomatic abnormalities that predict progression to clinical disease.

"Tool-in-lesion" Accuracy of Galaxy System-A Robotic Electromagnetic Navigation BroncHoscopy With Integrated Tool-in-lesion-Tomosynthesis Technology: The MATCH Study.

BACKGROUND: The Galaxy System (Noah Medical) is a novel robotic endoluminal platform using electromagnetic navigation combined with integrated tomosynthesis technology and augmented fluoroscopy. It provides intraprocedural imaging to correct computerized tomography (CT) to body divergence and novel confirmation of tool-in-lesion (TIL). The primary aim of this study was to assess the TIL accuracy of the robotic bronchoscope with integrated digital tomosynthesis and augmented fluoroscopy. METHODS: Four operators conducted the experiment using 4 pigs. Each physician performed between 4 and 6 nodule biopsies for 20 simulated lung nodules with purple dye and a radio pacifier. Using Galaxy's "Tool-in-Lesion Tomography (TOMO+)" with augmented fluoroscopy, the physician navigated to the lung nodules, and a tool (needle) was placed into the lesion. TIL was defined by the needle in the lesion determined by cone-beam CT. RESULTS: The lung nodule's average size was 16.3 ± 0.97 mm and was predominantly in the lower lobes (65%). All 4 operators successfully navigated to all (100%) of the lesions in an average of 3 minutes and 39 seconds. The median number of tomosynthesis sweeps was 3 and augmented fluoroscopy was utilized in most cases (17/20 or 85%). TIL after the final TOMO sweep was 95% (19/20) and tool-touch-lesion was 5% (1/20). Biopsy yielding purple pigmentation was also 100% (20/20). CONCLUSION: The Galaxy System demonstrated successful digital TOMO confirmed TIL success in 95% (19/20) of lesions and tool-touch-lesion in 5% (1/20) as confirmed by cone-beam CT. Successful diagnostic yield was achieved in 100% (20/20) of lesions as confirmed by intralesional pigment acquisition.

Diagnostic Yield vs Diagnostic Accuracy for Peripheral Lung Biopsy Evaluation: Evidence Supporting a Future Pragmatic End Point.

BACKGROUND: Diagnostic yield and accuracy endpoints have been used inconsistently in the evaluation of advanced diagnostic bronchoscopy devices and techniques, limiting between-study comparisons. In addition, diagnostic accuracy can be adjudicated only after prolonged clinical follow-up, which delays reporting on the performance of novel devices. RESEARCH QUESTION: Will a conservative diagnostic yield definition result in few false-negative initial results to closely approximate diagnostic accuracy and represent a useful outcome for future studies of diagnostic utility? METHODS: Commonly used definitions of diagnostic yield were applied to a prospective data set of consecutive peripheral pulmonary lesions sampled by navigational bronchoscopy from 2017 to 2019. All consider malignancy to be diagnostic but differ in their classification of nonmalignant biopsy findings, which were subcategorized as specific benign, nonspecific benign, or normal lung. Diagnostic yield calculations were also compared with diagnostic accuracy, defined as the proportion of biopsy specimens deemed diagnostic by each definition that were confirmed accurate through 2 years of follow-up. RESULTS: A total of 450 biopsy specimens of lesions were analyzed. The prevalence of malignancy was 60.9% (274 of 450). On initial bronchoscopy pathology, there were 227 malignant diagnoses (50.4%), with a single false positive (0.4%). Among 104 biopsy specimens with specific benign findings, only two were false negative for malignancy (1.9%). There were 119 nonspecific benign biopsy specimens, with 46 false negatives for malignancy (38.7%). The discrepancy between diagnostic yield and accuracy was 0.7% for the conservative definition, which only considered malignant or specific benign findings as diagnostic. INTERPRETATION: A conservative diagnostic yield definition excluding nonspecific benign diagnoses closely approximated diagnostic accuracy through 2 years' follow-up, with a less than 1% discrepancy. Using this conservative yield definition may allow for dissemination of reliable diagnostic utility data without protracted delays needed for follow-up data in this era of rapid technological change in advanced diagnostic bronchoscopy.

Robotic versus Electromagnetic bronchoscopy for pulmonary LesIon AssessmeNT: the RELIANT pragmatic randomized trial.

BACKGROUND: Robotic-assisted bronchoscopy has recently emerged as an alternative to electromagnetic navigational bronchoscopy for the evaluation of peripheral pulmonary lesions. While robotic-assisted bronchoscopy is proposed to have several advantages, such as an easier learning curve, it is unclear if it has comparable diagnostic utility as electromagnetic navigational bronchoscopy. METHODS: Robotic versus Electromagnetic bronchoscopy for pulmonary LesIon AssessmeNT (RELIANT) is an investigator-initiated, single-center, open label, noninferiority, cluster randomized controlled trial conducted in two operating rooms at Vanderbilt University Medical Center. Each operating room (OR) is assigned to either robotic-assisted or electromagnetic navigational bronchoscopy each morning, with each OR day considered one cluster. All patients undergoing diagnostic bronchoscopy for evaluation of a peripheral pulmonary lesion in one of the two operating rooms are eligible. Schedulers, patients, and proceduralists are blinded to daily group allocations until randomization is revealed for each operating room each morning. The primary endpoint is the diagnostic yield defined as the proportion of cases yielding lesional tissue. Secondary and safety endpoints include procedure duration and procedural complications. Enrolment began on March 6, 2023, and will continue until 202 clusters have been accrued, with expected enrolment of approximately 400 patients by the time of completion in March of 2024. DISCUSSION: RELIANT is a pragmatic randomized controlled trial that will compare the diagnostic yield of the two most commonly used bronchoscopic approaches for sampling peripheral pulmonary lesions. This will be the first known cluster randomized pragmatic trial in the interventional pulmonology field and the first randomized controlled trial of robotic-assisted bronchoscopy. TRIAL REGISTRATION: ClinicalTrials.gov registration (NCT05705544) on January 30, 2023.

Spray Cryotherapy for Benign Large Airway Stenosis: A Multicenter Retrospective Cohort Study of Safety and Practice Patterns.

BACKGROUND: Benign airway stenosis (BAS) represents a significant burden on patients, providers, and healthcare systems. Spray cryotherapy (SCT) has been proposed as an adjunctive treatment to reduce BAS recurrence. We sought to examine safety and practice variations of the latest SCT system when used for BAS. METHODS: We conducted a retrospective multicenter cohort study in seven academic institutions within the Interventional Pulmonary Outcomes Group. All patients who underwent at least one SCT session with a diagnosis of BAS at the time of procedure at these institutions were included. Demographics, procedure characteristics, and adverse events were captured through each center's procedural database and electronic health record. RESULTS: A total of 102 patients underwent 165 procedures involving SCT from 2013 to 2022. The most frequent etiology of BAS was iatrogenic (n = 36, 35%). In most cases, SCT was used prior to other standard BAS interventions (n = 125; 75%). The most frequent SCT actuation time per cycle was five seconds. Pneumothorax complicated four procedures, requiring tube thoracostomy in two. Significant post-SCT hypoxemia was noted in one case, with recovery by case conclusion and no long-term effects. There were no instances of air embolism, hemodynamic compromise, or procedural or in-hospital mortality. CONCLUSION: SCT as an adjunctive treatment for BAS was associated with a low rate of complications in this retrospective multicenter cohort study. SCT-related procedural aspects varied widely in examined cases, including actuation duration, number of actuations, and timing of actuations relative to other interventions.

Shape-Sensing Robotic-Assisted Bronchoscopy vs Digital Tomosynthesis-Corrected Electromagnetic Navigation Bronchoscopy: A Comparative Cohort Study of Diagnostic Performance.

BACKGROUND: Electromagnetic navigational bronchoscopy has been the dominant bronchoscopic technology for targeting small peripheral lesions and now includes digital tomosynthesis-electromagnetic navigational bronchoscopy (DT-ENB), allowing near-real-time intraprocedural nodule visualization. Shape-sensing robotic-assisted bronchoscopy (ssRAB), with improved catheter stability and articulation recently became available. Although the diagnostic performance of these two methods seems higher than that of legacy systems, data remain limited. We sought to compare the diagnostic yield of these two novel platforms after their introduction at our institution. RESEARCH QUESTION: Does the diagnostic yield of ssRAB differ significantly from that of DT-ENB in patients undergoing biopsy of peripheral pulmonary lesions (PPLs)? STUDY DESIGN AND METHODS: This retrospective comparative cohort study analyzed prospectively collected data on consecutive procedures performed with DT-ENB and ssRAB in their first 6 months of use at our institution. Biopsies were considered diagnostic if histopathologic analysis revealed malignancy or specific benign features that readily explained the presence of a PPL. Nonspecific inflammation, normal lung or airway, and atypia not diagnostic of malignancy were considered nondiagnostic. RESULTS: SSRAB was used to biopsy 143 PPLs in 133 patients and DT-ENB was used to biopsy 197 PPLs in 170 patients. Diagnostic yield was 77% for ssRAB (110 of 143 PPLs) and 80% (158 of 197 PPLs) for DT-ENB (OR, 0.8; 95% CI, 0.5-1.4; P = .4). Median lesion diameters were 17 and 19 mm, respectively. No difference in diagnostic yield was found after adjustment for lesion size, bronchus sign, peripheral vs middle third location, and sex. Pneumothorax complicated 1.5% of ssRAB and 1.8% of DT-ENB procedures (P = .86). INTERPRETATION: SSRAB and DT-ENB showed comparable diagnostic yields and safety profiles in this comparative cohort study.

Inter-rater reliability of a novel objective endpoint for benign central airway stenosis interventions: Segmentation-based volume rendering of computed tomography scans.

OBJECTIVES: To evaluate the reliability of a novel segmentation-based volume rendering approach for quantification of benign central airway obstruction (BCAO). DESIGN: A retrospective single-center cohort study. SETTING: Data were ascertained using electronic health records at a tertiary academic medical center in the United States. PARTICIPANTS AND INCLUSION: Patients with airway stenosis located within the trachea on two-dimensional (2D) computed tomography (CT) imaging and documentation of suspected benign etiology were included. Four readers with varying expertise in quantifying tracheal stenosis severity were selected to manually segment each CT using a volume rendering approach with the available free tools in the medical imaging viewing software OsiriX (Bernex, Switzerland). Three expert thoracic radiologists were recruited to quantify the same CTs using traditional subjective methods on a continuous and categorical scale. OUTCOME MEASURES: The interrater reliability for continuous variables was calculated by the intraclass correlation coefficient (ICC) using a two-way mixed model with 95% confidence intervals (CI). RESULTS: Thirty-eight patients met the inclusion criteria, and fifty CT scans were selected for measurement. The most common etiology of BCAO was iatrogenic in 22 patients (58%). There was an even distribution of chest and neck CT imaging within our cohort. The average ICC across all four readers for the volume rendering approach was 0.88 (95% CI, 0.84 to 0.93), suggesting good to excellent agreement. The average ICC for thoracic radiologists for subjective methods on the continuous scale was 0.38 (95% CI, 0.20 to 0.55), suggesting poor to fair agreement. The kappa for the categorical approach was 0.26, suggesting a slight to fair agreement amongst the raters. CONCLUSION: In this retrospective cohort study, agreement was good to excellent for raters with varying expertise in airway cross-sectional imaging using a novel segmentation-based volume rendering approach to quantify BCAO. This proposed measurement outperformed our expert thoracic radiologists using conventional subjective grading methods.

Robotic versus Electromagnetic Bronchoscopy for Pulmonary LesIon AssessmeNT: the RELIANT pragmatic randomized trial.

Background: Robotic assisted bronchoscopy has recently emerged as an alternative to electromagnetic navigational bronchoscopy for the evaluation of peripheral pulmonary lesions. While robotic assisted bronchoscopy is proposed to have several advantages, such as an easier learning curve, it is unclear if it has comparable diagnostic utility as electromagnetic navigational bronchoscopy. Methods: Robotic versus Electromagnetic Bronchoscopy for Pulmonary LesIon AssessmeNT (RELIANT) is an investigator-initiated, single-center, open label, noninferiority, cluster randomized controlled trial conducted in two operating rooms at Vanderbilt University Medical Center. Each operating room is assigned to either robotic assisted or electromagnetic navigational bronchoscopy each morning, with each OR day considered one cluster. All patients undergoing diagnostic bronchoscopy for evaluation of a peripheral pulmonary lesion in one of the two operating rooms are eligible. Schedulers, patients and proceduralists are blinded to daily group allocations until randomization is revealed for each operating room each morning. The primary endpoint is the diagnostic yield defined as the proportion of cases yielding lesional tissue. Secondary and safety endpoints include procedure duration and procedural complications. Enrolment began on March 6, 2023, and will continue until 202 clusters have been accrued, with expected enrolment of approximately 400 patients by the time of completion in March of 2024. Discussion: RELIANT is a pragmatic randomized controlled trial that will compare the diagnostic yield of the two most commonly used bronchoscopic approaches for sampling peripheral pulmonary lesions. This will be the first known cluster randomized pragmatic trial in the interventional pulmonology field and the first randomized controlled trial of robotic assisted bronchoscopy. Trial registration: ClinicalTrials.gov registration (NCT05705544) on January 30, 2023.

The Thoracic Research Evaluation and Treatment 2.0 Model: A Lung Cancer Prediction Model for Indeterminate Nodules Referred for Specialist Evaluation.

BACKGROUND: Appropriate risk stratification of indeterminate pulmonary nodules (IPNs) is necessary to direct diagnostic evaluation. Currently available models were developed in populations with lower cancer prevalence than that seen in thoracic surgery and pulmonology clinics and usually do not allow for missing data. We updated and expanded the Thoracic Research Evaluation and Treatment (TREAT) model into a more generalized, robust approach for lung cancer prediction in patients referred for specialty evaluation. RESEARCH QUESTION: Can clinic-level differences in nodule evaluation be incorporated to improve lung cancer prediction accuracy in patients seeking immediate specialty evaluation compared with currently available models? STUDY DESIGN AND METHODS: Clinical and radiographic data on patients with IPNs from six sites (N = 1,401) were collected retrospectively and divided into groups by clinical setting: pulmonary nodule clinic (n = 374; cancer prevalence, 42%), outpatient thoracic surgery clinic (n = 553; cancer prevalence, 73%), or inpatient surgical resection (n = 474; cancer prevalence, 90%). A new prediction model was developed using a missing data-driven pattern submodel approach. Discrimination and calibration were estimated with cross-validation and were compared with the original TREAT, Mayo Clinic, Herder, and Brock models. Reclassification was assessed with bias-corrected clinical net reclassification index and reclassification plots. RESULTS: Two-thirds of patients had missing data; nodule growth and fluorodeoxyglucose-PET scan avidity were missing most frequently. The TREAT version 2.0 mean area under the receiver operating characteristic curve across missingness patterns was 0.85 compared with that of the original TREAT (0.80), Herder (0.73), Mayo Clinic (0.72), and Brock (0.68) models with improved calibration. The bias-corrected clinical net reclassification index was 0.23. INTERPRETATION: The TREAT 2.0 model is more accurate and better calibrated for predicting lung cancer in high-risk IPNs than the Mayo, Herder, or Brock models. Nodule calculators such as TREAT 2.0 that account for varied lung cancer prevalence and that consider missing data may provide more accurate risk stratification for patients seeking evaluation at specialty nodule evaluation clinics.

Navigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trial.

Background: Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant etiologies. The gold-standard for minimally invasive biopsy, computed tomography-guided transthoracic needle biopsy (CT-TTNB), has never been directly compared to navigational bronchoscopy, a modality which has recently seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rate. Current estimates of the diagnostic utility of both modalities are based largely on non-comparative data with significant risk for selection, referral, and publication biases. Methods: The VERITAS trial (na V igation E ndoscopy to R each Indeterminate lung nodules versus T ransthoracic needle A spiration, a randomized controlled S tudy) is a multicenter, 1:1 randomized, parallel-group trial designed to ascertain whether electromagnetic navigational bronchoscopy with integrated digital tomosynthesis is noninferior to CT-TTNB for the diagnosis of peripheral lung nodules 10-30 mm in diameter with pre-test probability of malignancy of at least 10%. The primary endpoint is diagnostic accuracy through 12 months follow-up. Secondary endpoints include diagnostic yield, complication rate, procedure duration, need for additional invasive diagnostic procedures, and radiation exposure. Discussion: The results of this rigorously designed trial will provide high-quality data regarding the management of lung nodules, a common clinical entity which often represents the earliest and most treatable stage of lung cancer. Several design challenges are described. Notably, all nodules are centrally reviewed by an independent interventional pulmonology and radiology adjudication panel relying on pre-specified exclusions to ensure enrolled nodules are amenable to sampling by both modalities while simultaneously protecting against selection bias favoring either modality. Conservative diagnostic yield and accuracy definitions with pre-specified criteria for what non-malignant findings may be considered diagnostic were chosen to avoid inflation of estimates of diagnostic utility. Trial registration: ClinicalTrials.gov NCT04250194.

Endobronchial Therapies for Diagnosis, Staging, and Treatment of Lung Cancer.

Lung cancer is the leading cause of cancer-related death worldwide and within the United States. Although evidence-based screening has been shown to reduce cancer-related mortality, the late-stage presentation remains common. Bronchoscopy has been proven to be an essential tool in the diagnosis and management of lung cancer. Basic and advanced diagnostic bronchoscopic techniques offer a minimally invasive modality for diagnosing and staging patients with lung cancer. In patients with malignant endotracheobronchial disease, therapeutic bronchoscopy (flexible or rigid) is a safe procedure that palliates symptoms such as dyspnea and hemoptysis. In this article, we review the various endobronchial tools and strategies essential for the management of lung cancer.

Association between terminal pleural elastance and radiographic lung re-expansion after therapeutic thoracentesis in patients with symptomatic pleural effusion: a post-hoc analysis of a randomised trial.

OBJECTIVES: Recurrent symptomatic effusions can be durably managed with pleurodesis or placement of indwelling pleural catheters. Recent pleurodesis trials have largely relied on lung re-expansion on post-thoracentesis radiograph as an inclusion criterion rather than pleural elastance as determined by manometry, which is an important predictor of successful pleurodesis. We investigated the association between lung re-expansion on post-pleural drainage chest imaging and pleural physiology, with particular attention to pleural elastance over the final 200 mL aspirated. DESIGN: Post-hoc analysis of a recent randomised trial. SETTING AND PARTICIPANTS: Post-results analysis of 61 subjects at least 18 years old with symptomatic pleural effusions estimated to be at least of 0.5 L in volume allocated to manometry-guided therapeutic thoracentesis in a recent randomised trial conducted at two major university hospitals in the USA. PRIMARY OUTCOME MEASURES: The primary outcome was concordance of radiographic with normal terminal pleural elastance over the final 200 mL aspirated. We label this terminal elastance 'visceral pleural recoil', or the tendency of the maximally expanded lung to withdraw from the chest wall. RESULTS: Post-thoracentesis chest radiograph and thoracic ultrasound indicated successful lung re-expansion in 69% and 56% of cases, respectively. Despite successful radiographic lung re-expansion, visceral pleural recoil was abnormal in 71% of subjects expandable by radiograph and 77% expandable by ultrasound. The sensitivity and positive predictive value of radiographic lung re-expansion for normal visceral pleural recoil were 44% and 24%, respectively. CONCLUSION: Radiographic lung re-expansion by post-thoracentesis chest radiograph or thoracic ultrasound is a poor surrogate for normal terminal pleural elastance. Clinical management of patients with recurrent symptomatic pleural effusions guided by manometry rather than post-thoracentesis imaging might produce better outcomes, which should be investigated by future clinical trials. TRIAL REGISTRATION NUMBER: NCT02677883; Post-results.

A multidisciplinary approach to the work up and management of pulmonary carcinoid tumors and DIPNECH: a narrative review.

Background and Objective: Low and intermediate grade neuroendocrine tumors of the lung are uncommon malignancies representing 2% of all lung cancers. These are termed typical and atypical pulmonary carcinoid tumors. These can arise in the setting of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). The presentation, workup, management and outcomes of patients with these tumors can overlap with more common lung cancers but differ in that many of these patients have a prolonged clinical course. The objective of this narrative review is to summarize the literature and provide evidence and expert-based algorithms for work up and treatment of pulmonary carcinoids and DIPNECH. Methods: A search of PubMed and Web of Science databases ending April 15, 2022, with the following keywords "lung carcinoid", "DIPNECH", "lung neuroendocrine," and "bronchopulmonary carcinoid". Key Content and Findings: Pulmonary carcinoid tumors benefit from a multidisciplinary approach. Pre-treatment imaging with contrast-enhanced computed tomography, and DOTATATE positron emission tomography is required. Surgical resection is the gold standard for curative intent, and possibly including sublobar resections. Patients can recur or develop new primaries thus emphasizing the importance of surveillance; national guidelines recommend at least a 10-year follow up. A growing body of literature support the use of endobronchial therapy, with long responses documented. Systemic therapy consists of everolimus, somatostatin analogs, peptide receptor radionuclide therapy, and chemotherapy. Diffuse idiopathic pulmonary neuroendocrine tumor cell hyperplasia is rare, but series suggest somatostatin analogs may confer clinical benefit. Conclusions: Pulmonary carcinoid tumors and DIPNECH are rare. Despite lack of regulatory approvals for advanced disease, multiple options are available but should be sequenced according to the clinical status and disease biology. Each patient should be discussed in a multidisciplinary setting and clinical trials should be considered if available.

Fluorescence in situ hybridization testing algorithm improves lung cancer detection in bronchial brushing specimens.

RATIONALE: Bronchoscopically collected cytology specimens are commonly used to obtain a diagnosis of cancer in patients with pulmonary lesions. However, the sensitivity of cytology is suboptimal, especially for peripheral lesions less than 2 cm in diameter. OBJECTIVES: We assessed the performance of a testing algorithm using cytology and fluorescence in situ hybridization (FISH) as part of clinical practice. METHODS: Bronchial brushing specimens (n = 343) were obtained from patients undergoing bronchoscopy for indeterminate pulmonary lesions. Routine cytology was performed and specimens without a positive diagnosis (n = 294) were analyzed by FISH, using residual brushing material. Pathology-confirmed lung cancer or clinical/radiographic evidence of disease was considered diagnostic of malignancy. MEASUREMENTS AND MAIN RESULTS: Routine cytology had a sensitivity and specificity of 41% (23 of 56) and 100% (45 of 45) for central lesions and 20% (26 of 133) and 100% (109 of 109) for peripheral nodules, respectively. FISH detected an additional 32% of lung cancers (18 central and 43 peripheral) not detectable by cytology alone, while producing false positive diagnoses in 22% (10 of 45) and 6% (6 of 109) benign central and peripheral lesions, respectively. In peripheral nodules, FISH detected (relative to routine cytology) an additional 44% (15 of 34) and 28% (25 of 91) of lung cancers less than 2 cm and 2 cm or more in size, respectively. A positive FISH result had a likelihood ratio of 1.45 and 5.87 for central and peripheral lesions and 3.44 and 15.38 for peripheral nodules less than 2 cm and 2 cm or more in size, respectively. CONCLUSIONS: FISH testing significantly increases the detection of lung cancer over routine cytology alone. It is especially useful for peripheral nodules.

Advanced Bronchoscopic Technologies for Biopsy of the Pulmonary Nodule: A 2021 Review.

The field of interventional pulmonology (IP) has grown from a fringe subspecialty utilized in only a few centers worldwide to a standard component in advanced medical centers. IP is increasingly recognized for its value in patient care and its ability to deliver minimally invasive and cost-effective diagnostics and treatments. This article will provide an in-depth review of advanced bronchoscopic technologies used by IP physicians focusing on pulmonary nodules. While most pulmonary nodules are benign, malignant nodules represent the earliest detectable manifestation of lung cancer. Lung cancer is the second most common and the deadliest cancer worldwide. Differentiating benign from malignant nodules is clinically challenging as these entities are often indistinguishable radiographically. Tissue biopsy is often required to discriminate benign from malignant nodule etiologies. A safe and accurate means of definitively differentiating benign from malignant nodules would be highly valuable for patients, and the medical system at large. This would translate into a greater number of early-stage cancer detections while reducing the burden of surgical resections for benign disease. There is little high-grade evidence to guide clinicians on optimal lung nodule tissue sampling modalities. The number of novel technologies available for this purpose has rapidly expanded over the last decade, making it difficult for clinicians to assess their efficacy. Unfortunately, there is a wide variety of methods used to determine the accuracy of these technologies, making comparisons across studies impossible. This paper will provide an in-depth review of available data regarding advanced bronchoscopic technologies.

A Survey-Based Study of Patient-Centered Costs Associated With Indwelling Pleural Catheters.

INTRODUCTION: Indwelling pleural catheters (IPC) are effective at palliating benign and malignant pleural effusions (MPE). They have also been found to be cost effective from a third-party payor perspective. Little is known of the impact IPCs have on patient-centered quality of life outcomes such as financial burden and patient and caregiver burden. We performed a cross-sectional survey study evaluating the impact of IPCs on multiple patient and caregiver quality of life metrics. METHODS: Patients ≥ 18 years old with an IPC in place for 2 months were eligible. Twenty patients were recruited over a 10-month period. Patients completed the CDC-Health Related Quality of Life (HRQOL)-4 and a HRQOL-financial questionnaire. The primary objective was to describe the socio-economic impact of IPCs. Demographic and IPC specific data were collected. Descriptive statistics were used. RESULTS: The mean (SD) age was 64.3 (0.70). The indication was MPE in 19/20. All patients had medical insurance. Medicare or Medicaid (CMS) comprised 10/20 of payors. The median (IQR) copay for private insurers was $238.45 (72-875); 11/20 had additional costs related to the IPC; 4/20 had significant life changes after the IPC; 17/20 received assistance from a non-paid caregiver; 6/20 patients could not do activities because of the IPC and this negatively impacted QOL in 3/6 of those patients. CONCLUSION: Patients with IPCs may experience negative life consequences, incur additional medical expenses, and require assistance from a non-paid caregiver. Activities may be negatively impacted by IPC. Discussion of alternative means of symptom palliation and pleurodesis would be beneficial.