Endobronchial Ultrasound-guided Sampling of Centrally Located Intrapulmonary Tumors Provides Suitable Material for Diagnostic and Molecular Testing.

BACKGROUND: Curvilinear endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a key diagnostic and staging procedure for patients with suspected lung cancer. However, sampling centrally located intrapulmonary tumors is feasible but less well established. METHODS: We retrospectively evaluated the diagnostic utility of EBUS-TBNA in patients who underwent sampling of centrally located intrapulmonary tumors. Diagnostic accuracy, sample suitability for molecular testing, and complications were assessed. RESULTS: Between January 2015 and April 2021, 102 EBUS-TBNA procedures sampled centrally located intrapulmonary tumors in 99 patients. The median age was 70 [interquartile range, 63 to 75] years and 51% (51/99) were male. The commonest site was the right upper lobe (n=42/99; 42%). The median tumor size was 29 [interquartile range, 21 to 35] mm. The diagnostic yield was 88/102 (86%) with a false negative rate of 14% (14/102). In addition to intrapulmonary tumor sampling, lymph nodes were sampled in 65/102 procedures and 30/65(46%) were positive for lung cancer. Cancer was diagnosed in 87/99 (88%) cases. When requested, molecular testing was adequate in ≥94% of samples. Complications included minor bleeding in 6/102 (6%) with 2 requiring cold saline instillation, desaturation in 1/102 (1%), and tachycardia in 1/102(1%). One procedure was abandoned due to patient tachycardia. Delayed complications occurred in 1 patient who was hospitalized ≤7 days with pneumonia. CONCLUSION: EBUS-TBNA sampling of centrally located intrapulmonary tumors provides similar diagnostic accuracy to lymph node sampling, provides suitable material for molecular testing, and has a low complication rate.

Time between endobronchial ultrasound needle passes as a metric to monitor progress of trainees.

BACKGROUND: Methods to assess and track progress of new endobronchial ultrasound (EBUS) operators and trainees is desirable to ensure training goals and procedural competence are achieved. Relying on the diagnostic yield or on question-based assessments alone is not sufficient. This study examined the longitudinal change in times taken between needle passes (needle pass time; NPT) during EBUS lymph node sampling as a metric to monitor progress. RESEARCH DESIGN AND METHODS: :The EBUS database of a tertiary hospital was accessed to extract data on the first 50 EBUS procedures for three trainees. The NPT was derived using PACS images that are stored to document every needle pass during an EBUS procedure and an average NPT was calculated. RESULTS: Between the three trainees, 157 procedures were carried out within the study period with 302 nodal stations sampled. The mean NPT (n = 204 stations) was 2:49 ± 0:49 mins. The mean node short axis diameter was 15.5 ± 8.7 mm. There was a negative correlation between node size and time per pass (r - 0.146, p = 0.045).The average NPT showed a negative correlation with procedure order through the first 50 procedures. Less variation between procedures was noted for the three trainees from the 30th procedure onward. On multivariate regression, NPT was significantly associated with procedure order regardless of station sampled or lymph node diameter. CONCLUSION: NPT is novel, easy, and robust metric that can potentially help ensure EBUS trainees are advancing in a given training program.

Focused Neck Ultrasound and Lymph Node Sampling by Respiratory Physicians in Suspected Lung Cancer.

BACKGROUND: Malignant cervical lymphadenopathy in the setting of lung cancer represents N3 disease, and neck ultrasound (NUS) with sampling is described in the Royal College of Radiologists ultrasound training curriculum for the non-radiologists. This study reviews the incorporation of NUS +/- biopsy in the routine practice of a lung cancer fast-track clinic in the UK. METHODS: We retrospectively assessed 29 months of activity of a lung cancer fast-track clinic. Systematic focused NUS was conducted in suspected thoracic malignancy, sampling nodes with a ≥5-mm short axis, under real-time US using a linear probe (5-12 Mhz). Fine-needle aspirations (FNAs) with or without 18 Ga core biopsies were taken. RESULTS: Between August 2017 and December 2019, of 152 peripheral lymph nodes (LNs)/deposits sampled, 98 (64.5%) were supraclavicular fossa LNs with median [IQR] size 12 [8-18] mm. Core biopsies were performed in 54/98 (55%) patients, while all patients had FNAs. No complications occurred. The representative yield was 90/95 (94.7%) in cases with suspected cancer. No difference was seen between FNA versus core biopsy (p = 0.44). Of the 5 non-diagnostic samples, one was FNA only. The commonest diagnosis was lung cancer in 66/98 (67.3%). PDL-1 was sufficient in 35/36 tested (97.2%). ALK-FISH was successful in 24/25 (96%) cases. EGFR mutation analysis was successful in 28/31 (90.3%) cases. Median time from clinic to initial diagnosis was 7 [5-10] days. Computed tomography (CT) scans reported no significant lymphadenopathy in 18/96 (18.7%) cases, yet 10/18 (55.5%) cases were positive for malignancy. CONCLUSION: Neck nodal sampling by respiratory physicians was safe, timely, with a high diagnostic yield and suitability for molecular testing. Neck US can provide a timely diagnosis in cases that may be missed by CT alone.

Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory. METHODS: A multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure. RESULTS: A total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557-0.664], p = 0.0015) and 0.516 [0.443-0.589], p = 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume. CONCLUSIONS: SOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification.

Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study.

BACKGROUND: Over 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter. OBJECTIVES: To prospectively assess a previously described risk score (the RAPID (Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) score) in adults with pleural infection. METHODS: Prospective observational cohort study that recruited patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment and lung function at 3 months. RESULTS: Mortality data were available in 542 out of 546 patients recruited (99.3%). Overall mortality was 10% at 3 months (54 out of 542) and 19% at 12 months (102 out of 542). The RAPID risk category predicted mortality at 3 months. Low-risk mortality (RAPID score 0-2): five out of 222 (2.3%, 95% CI 0.9 to 5.7%); medium-risk mortality (RAPID score 3-4): 21 out of 228 (9.2%, 95% CI 6.0 to 13.7%); and high-risk mortality (RAPID score 5-7): 27 out of 92 (29.3%, 95% CI 21.0 to 39.2%). C-statistics for the scores at 3 months and 12 months were 0.78 (95% CI 0.71-0.83) and 0.77 (95% CI 0.72-0.82), respectively. CONCLUSIONS: The RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population.

Routine neck ultrasound by respiratory physicians in the diagnosis and staging of patients with lung cancer and mediastinal lymphadenopathy: a prospective pilot study.

INTRODUCTION: Cervical lymphadenopathy in lung cancer indicates advanced disease. The presence of mediastinal lymphadenopathy is commonly associated with involvement of neck lymph nodes and some studies suggest routine neck ultrasound (NUS) in this group of patients. We conducted a two-phase study looking at training a respiratory physician to perform ultrasound-guided neck lymph node aspiration in patients with suspected lung cancer. METHODS: In the first phase of the study, one of the authors underwent training in NUS according to predetermined criteria. The adequacy of sampling was prospectively recorded. In the second phase, consecutive patients with suspected lung cancer and mediastinal lymphadenopathy underwent NUS and sampling of abnormal lymph nodes. The outcomes were the adequacy of samples for pathological analysis and molecular analysis, prevalence of cervical lymphadenopathy, and change in stage. RESULTS: Following the period of training, 35 patients underwent neck node sampling with an overall adequacy of 88.6% (95% CI 78.1-99.1%). Cervical lymph node involvement was confirmed in 13 out of 30 patients with lung cancer (43.3%, 95% CI 25.5-62.6%). Further immunohistochemistry and molecular studies were possible in all patients when it was required (nine cases). NUS led to nodal upstaging in four out of 30 (13.3%) cases. CONCLUSION: Training a respiratory physician to perform NUS and needle sampling to an acceptable level is feasible. Benefits of embedding this procedure in lung cancer diagnosis and pathway staging need to be explored in further studies.

Prevalence and outcome of central airway obstruction in patients with lung cancer.

Introduction: Central airway obstruction (CAO) is a life-threatening complication of lung cancer. The prevalence of CAO in lung cancer patients is unknown. We audited CAO burden to inform our local cancer service. Methods: This is a cohort review of all new lung cancer diagnoses between 1 November 2014 and 30 November 2015. CAO was defined by CT appearance. CT scans and routine patient records were followed up to 30 November 2018 to determine the prevalence of CAO at diagnosis; the characteristics of patients with prevalent CAO; mortality (using survival analysis); and incident CAO over follow-up. Results: Of 342 new lung cancer diagnoses, CAO prevalence was 13% (95% CI 10% to 17%; n=45/342). Dedicated CT scan review identified missed CAO in 14/45 (31%) cases. In patients with prevalent CAO, 27/44 (61%) had a performance status of ≤2, 23/45 (51%) were diagnosed during an acute admission and 36/44 (82%) reported symptoms. Treatments were offered to 32/45 (71%); therapeutic bronchoscopy was performed in only 8/31 (26%) eligible patients. Median survival of patients with prevalent CAO was 94 (IQR 33-274) days. Multivariate analysis, adjusting for age, gender and disease stage, found CAO on index CT scan was independently associated with an increased hazard of death (adjusted HR 1.78 (95% CI 1.27 to 2.48); p=0.001). In total, 15/297 (5%) developed CAO during follow-up (median onset 340 (IQR 114-551) days). Over the audit period, 60/342 (18%; 95% CI 14% to 22%) had or developed CAO. Discussions: This is the first description of CAO prevalence in 40 years. Patients with prevalent CAO had a higher mortality. Our data provide a benchmark for service planning.

Neck Ultrasound for the Detection of Cervical Lymphadenopathy in Sarcoidosis: An Alternative to Endobronchial Ultrasound.

BACKGROUND: Sarcoidosis is diagnosed by demonstration of granulomatous inflammation and exclusion of other potential causes. Lung parenchyma and intrathoracic lymph nodes are currently the commonest sites from which tissue is obtained in clinical practice, but historically scalene lymph node biopsy was the procedure of choice for diagnosing sarcoidosis in many institutions. AIM: We aimed to assess the utility of neck ultrasound (NUS) and cervical lymph node needle sampling among patients with stage 1 and 2 sarcoidosis. In addition, we analyzed the potential predictors of cervical lymphadenopathy in this retrospective cohort study. METHODS: Patients with evidence of intrathoracic lymphadenopathy and suspected sarcoidosis referred for an endobronchial ultrasound underwent NUS. Those with enlarged cervical lymph nodes underwent fine-needle aspiration and core needle biopsy when technically feasible. RESULTS: A total of 38 patients were included of which 34 (89.5%) underwent endobronchial ultrasound. Sixteen patients had enlarged lymph nodes on ultrasound and 8 (50%) of these underwent needle sampling. Non-necrotizing granulomas were detected in 6 cases (16.8%, 95% confidence interval, 6.1%-31.3%). Cervical lymphadenopathy was significantly associated with the presence of upper paratracheal lymphadenopathy (P=0.018) and the size of mediastinal lymph nodes on computed tomography (P=0.011). CONCLUSION: NUS and needle sampling of cervical lymph nodes is a potential modality that can be used for the diagnosis of sarcoidosis in a selected group of patients.

Ultrasound-Guided Cervical Lymph Node Sampling Performed by Respiratory Physicians.

BACKGROUND: A variety of disease processes investigated by respiratory physicians can lead to cervical lymphadenopathy. Ultrasound (US) has revolutionised respiratory investigations, and neck ultrasound (NUS) is increasingly recognised as an additional important skill for respiratory physicians. OBJECTIVES: We aimed to assess the feasibility of NUS performed by respiratory physicians in the workup of patients with mediastinal lymphadenopathy. METHODS: This is a single-centre retrospective cohort study. All patients that underwent US-guided cervical lymph node sampling were included. The diagnostic yield is reported, and specimen adequacy is compared for respiratory physicians and radiologists. RESULTS: Over 5 years, 106 patients underwent NUS-guided lymph node sampling by respiratory physicians compared to 35 cases performed by radiologists. There was no significant difference in the adequacy of sampling between the two groups (respiratory physicians 91.5% [95% CI 84.5-96%] compared to 82.9% [95% CI 66.4-93.4%] for radiologists [p = 0.2]). In the respiratory physician group, a diagnosis was achieved based on lymph node sampling in 89 cases (84%). Neck lymph node sampling was the only procedure performed to obtain tissue in 48 cases (45.3%). CONCLUSION: NUS and sampling performed by respiratory physicians are feasible and associated with an adequacy rate comparable to that of radiologists. It can reduce the number of invasive procedures performed in a selected group of patients. Guidelines for training and competency assessment are required.

PET and Neck Ultrasound for the Detection of Cervical Lymphadenopathy in Patients with Lung Cancer and Mediastinal Lymphadenopathy.

BACKGROUND: Cervical lymph nodes are frequently involved in patients with lung cancer and indicate inoperability. Some guidelines recommend neck ultrasound (NUS) in patients with bulky mediastinal lymphadenopathy. Positron emission tomography (PET) is indicated for patients with potentially curable disease. OBJECTIVES: We aimed to assess the diagnostic yield of NUS and the diagnostic accuracy of PET for cervical lymphadenopathy in this group with a high pre-test probability of N3 disease. METHODS: Records of all patients with lung cancer who underwent an NUS over a consecutive 5-year period were reviewed. Only patients with mediastinal lymphadenopathy on computerised tomography (CT) were included. The diagnostic accuracy of PET was assessed with NUS-guided fine needle aspiration cytology used as the reference test. RESULTS: During the study period, 123 patients met the inclusion criteria. Malignant cervical lymphadenopathy was confirmed in 49/123 (39.8% [95% CI 31.1-49.1]). PET-CT had a specificity of 81.1%, sensitivity of 87.5%, negative predictive value of 96.8% and positive predictive value of 50% for the detection of cervical lymphadenopathy, and it contributed no additional staging information in the neck area. Overall, PET led to a change in management in only 2.2% of cases. CONCLUSION: A significant proportion of patients with lung cancer and mediastinal lymphadenopathy have cervical lymphadenopathy detected by NUS. In this group of patients, PET offers minimal additional value in staging and management.

The Art of Rigid Bronchoscopy and Airway Stenting.

Interventional pulmonology has grown significantly over the last 2 decades and is now seen as an essential component in thoracic oncology care. The rigid bronchoscope occupies a central role in this specialty and offers many important advantages over the flexible scope when performing therapeutic procedures on central airways. Although stenting practices have evolved, it is generally accepted that stents offer an important treatment option for selected patients with benign and malignant airway diseases. This article discusses rigid bronchoscopy and stenting, future challenges, complications of the procedure and stents, and future directions.

The role of a nurse specialist in a modern lung-cancer service.

The delivery of a modern cancer service is dependent on the nurse specialist occupying a central role in the overall pathway. However, there are significant variations in the access to a lung cancer clinical nurse specialist (CNS) across the UK and the USA. In the UK, the lung cancer CNS plays a pivotal role in the delivery of high-quality care and treatment to patients with (presumed) thoracic malignancy. They are in an ideal position to provide holistic care to patients with lung cancer-ensuring that all needs are addressed from the time of initial referral to commencement of definitive treatment or palliative care. In addition the role provides support and advice to people on the increasingly complex treatment options and on survivorship, and plays an essential role in end-of-life care. In the USA, the nurse navigator is a core member of the lung cancer screening programme. In this review the authors provide a transatlantic perspective on the history, current practice and potential future roles for the lung cancer CNS in the UK and nurse navigator in the US.

Role of interventional pulmonology in the management of complicated parapneumonic pleural effusions and empyema.

Pleural infection is a major problem that affects 80,000 cases per year in the UK and USA. It is increasing in incidence, and in an ageing population, it presents a complex challenge that requires a combination of medical therapies and may lead to the need for surgery. This article focuses on the role of the interventional pulmonologist in the diagnosis and management of pleural infection. In particular, we examine the role of pleural ultrasound in diagnostics, thoracocentesis and real-time guided procedures, and the current management strategies, including the controversial role of medical thoracoscopy.

Anti-inflammatory cytokines predominate in acute human Plasmodium knowlesi infections.

Plasmodium knowlesi has entered the human population of Southeast Asia. Naturally acquired knowlesi malaria is newly described with relatively little available data, including data on the host response to infection. Therefore pre-treatment cytokine and chemokine profiles were determined for 94 P. knowlesi, and for comparison, 20, P. vivax and 22 P. falciparum, patients recruited in Malaysian Borneo. Nine, five and one patient with P. knowlesi, P. falciparum and P. vivax respectively had complicated malaria as defined by World Health Organisation. Patients with uncomplicated P. knowlesi had lower levels of the pro-inflammatory cytokines IL-8 and TNFα than those with complicated disease (both p<0.05, Dunn's post test, DPT). The anti-inflammatory cytokines IL-1ra and IL-10 were detected in all patients in the study. IL-1ra, the most abundant cytokine measured, correlated with parasitaemia in P. knowlesi (r(s) = 0.47, p =  <0.0001), P. vivax (r(s) = 0.61, p = 0.0042) and P. falciparum (r(s) = 0.57,p = 0.0054) malaria. IL-10 correlated with parasitaemia in both P. knowlesi (r(s) = 0.54, p =  <0.0001) and P. vivax (r(s) = 0.78, p =  <0.0001) infections. There were between group differences in soluble markers of macrophage activation (MIP-1ß and MCP-1). P. knowlesi patients had significantly lower levels of MIP-1ß than P. falciparum (DPT, p =  <0.01). Uncomplicated P. knowlesi patients had significantly lower levels of MCP-1 than uncomplicated P. falciparum patients (DPT, p =  <0.001). There was no significant difference between complicated and uncomplicated P. knowlesi infections. MCP-1, MIP-1ß, IL-8 and TNFα increased in complicated P. knowlesi but decreased in complicated P. falciparum infections. Descriptions of human knowlesi malaria provide a comparative means to discover mediators of pathophysiology in severe P. knowlesi as well as P. falciparum malaria. Crucially, P. knowlesi may be the disease and experimental primate model for severe malaria.