The detection of Programmed Death Ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) has therapeutic implications for patients with advanced NSCLC.Previous studies have shown that PD-L1 in pleural fluid cytology is concordant to PD-L1 expression in tissue specimens.In 2020 the pathology laboratory in our centre recommended sending pleural fluid in formalin if PD-L1 analysis would be required, in accordance with prior PD-L1 studies in tissue specimens.In this single-centre study we assessed the adequacy of malignant pleural effusion (MPE) fluid for PD-L1 analysis, comparing the period before and after our pathology recommendation, and evaluating difference in yield between samples sent for cytology not in fixative compared to those sent in formalin. METHODS:All MPE from 2018-2019 (Period 1) and 2020-2022 (Period 2) were reviewed.Only pleural fluid samples positive for NSCLC were included.Data collection included histological subtype, if a sample was sent in formalin, and PD-L1 testing results.A total of 79 positive pleural fluids for malignancy were identified in Period 1, of which 26 were NSCLC and 6 of those were sent in formalin.In Period 2 there was 139 malignant pleural fluids, 44 of which were NSCLC.Of the 44 NSCLC in Period 2, 20 were sent in formalin.Pleural fluid samples were deemed as: sufficient for PD-L1 testing, insufficient for PD-L1 testing if the pathologists could not perform the analysis, and "unknown" if PD-L1 testing was not attempted. RESULTS:For the 26 samples in Period 1, 7 were sufficient for PD-L1 (26.92%), 8 were insufficient for PD-L1 (30.77%) and 11 samples had unknown PD-L1 adequacy status (42.31%).Period 2 had 15 samples sufficient for PD-L1 (34.09%), 14 were insufficient for PD-L1 (31.82%) and unknown sample adequacy in 15 (34.09%).In period 1, of the 7 samples which were PD-L1 sufficient, 4 had been in formalin compared to 3 without fixative; and insufficient in 1 sample from the formalin group as opposed to 10 samples in the no fixative group (P¼0.030;CI -95%, -4%).For period 2, 12 of the PD-L1 sufficient samples had been sent in formalin contrasted to 3 samples without fixative; and there were more PD-L1 insufficient samples in the no fixative group compared to the formalin group at 10 samples vs 4 samples respectively (P¼0.001;CI -83%,-20%).CONCLUSIONS: Pleural fluid yield for PD-L1 testing significantly increases if MPE samples are sent in formalin.CLINICAL IMPLICATIONS: Pleural fluid sampling is minimally invasive, and can be the first diagnostic investigation in patients presenting with advanced malignancy.We recommend that any patient undergoing diagnostic thoracocentesis with the suspicion of malignancy should have pleural fluid sent in formalin, and potentially decrease the need for more invasive investigations for PD-L1 analysis.
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. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
Toxic epidermal necrolysis and Staphylococcal scalded skin syndrome (SSSS) are potentially life-threatening dermatological emergencies that present in a similar clinical fashion. Toxic epidermal necrolysis is typically triggered by anticonvulsant and other neurological medications and reports clindamycin inducing the disease is exceedingly rare. SSSS seldomly occurs in adult patients. We present the case of a 60-year-old male presenting with dermatological rash covering >80% his body surface. Diagnosis and therapy involved multidisciplinary contribution from medical physicians, dermatologists, microbiologists and histopathologists to provide a favourable outcome.
Endobronchial metastasis from extrapulmonary malignancies are rare and include malignant melanoma. Cases that are complicated by central airway obstruction should follow a patient-centred approach, guided by patient and tumour characteristics. http://bit.ly/32baZvo.
Background and objectiveHiatal hernias (HH) are associated with gastro-oesophageal reflux and may contribute to lung disease severity. We aimed to evaluate the prevalence of HH among stable non-cystic fibrosis bronchiectasis (NCFB) patients and determine associations with disease severity.MethodsA retrospective cross-sectional cohort study of 100 consecutive NCFB patients in our institution was performed. Data were collected on baseline variables, microbiology, lung function and radiology, according to the modified Bhalla score. Disease severity was assessed using the Bronchiectasis Severity Index (BSI) and FACED severity scores.ResultsFollowing expert radiological review, 81 patients were deemed suitable for study inclusion (mean age (SD) 62.6 (12.4), females 55 (67.9%), body mass index (BMI) 26.9 (5.7)); 29 (35.8%) were HH positive (HH+). HH+ patients had a trend towards higher BMI (P=0.07), and a significantly higher proportion had reflux symptoms (HH+ 62.1% vs HH- 28.8%, P<0.01). The presence of HH+ was associated with cystic bronchiectasis (HH+ 30.1%, HH- 11.5%; P=0.03), increased number of lobes involved (HH+ 2.62 (1.54), HH- 2.17 (1.42); P=0.03), increased extent of bronchiectasis, (HH+ 6.2 (4.7), HH- 4.5 (3.1); P=0.04), decreased parenchymal attenuation (HH+ 1.0 (1.8), HH- 0.2 (0.5); P=0.03) and reduced percent predicted forced expiratory volume in 1s (HH+ 75.4% (24.5), HH- 90.4% (25.5); P=0.02). There was no lobar predilection. HH+ was associated with increased disease severity scores: BSI (HH+ 4.93 (1.65), HH- 3.25 (2.13); P<0.001) and FACED (HH+ 2.21 (1.52), HH- 1.35 (1.43); P<0.01).ConclusionsHH+ was associated with worse disease severity in NCFB patients, characterized by decreased lung function, increased extent and severity of radiological disease, and increased composite disease severity scores.This is the first study to evaluate the role of hiatal hernias in bronchiectasis. The presence of a hiatal hernia was associated with worse disease severity, characterized by decreased lung function, increased extent and severity of radiological disease, and increased composite disease severity scores.
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.
Medical thoracoscopy is an important technique for assessment of undiagnosed exudative pleural effusion. It is also important in the management of pleural disease, benign or malignant. Standard equipment available from several manufacturers enables the procedure to be performed through a single port of entry, frequently under conscious sedation. With good patient selection, thoracoscopy is a highly successful and safe procedure. Adequate training is mandatory and a period of mentoring is highly recommended. In this paper we discuss the use of thoracoscopy for some benign and malignant conditions and reveal that controversy remains over issues including the optimum mode and agent for pleurodesis. In addition, opinions differ on the precise role of thoracoscopy for pleural infection. In this paper we discuss key background information necessary for the safe provision of thoracoscopy. We then undertake a review of recent literature addressing important aspects of this procedure.