639 results found
Tsao M-S, Nicholson AG, Maleszewski JJ, et al., 2022, Introduction to 2021 WHO Classification of Thoracic Tumors., J Thorac Oncol, Vol: 17, Pages: e1-e4
Mackintosh JA, Wells AU, Cottin V, et al., 2021, Interstitial pneumonia with autoimmune features: challenges and controversies., Eur Respir Rev, Vol: 30
The presence of clinical, serological and/or radiological features suggestive, but not confirmatory, of a defined connective tissue disease in patients with interstitial lung disease is a relatively frequent occurrence. In 2015, the European Respiratory Society and the American Thoracic Society proposed classification criteria for the interstitial pneumonia with autoimmune features (IPAF) research entity to capture such patients in a standardised manner, with the intention of nurturing clinical research. This initiative resulted in the publication of several series of IPAF patients, with significant variation between cohorts in clinical characteristics, outcome and the application of IPAF criteria in patient selection. From this increasing body of published work, it has become apparent that revision of IPAF criteria is now required in order to justify the eventual designation of IPAF as a standalone diagnostic term, as opposed to a provisional entity put forward as a basis for clinical research. This review covers the current state of IPAF, conclusions that can and cannot be drawn from the IPAF evidence base, and ongoing uncertainties that require further expert group consideration.
Schulte JJ, Chapel DB, Attanoos R, et al., 2021, Comparison of Nuclear Grade, Necrosis, and Histologic Subtype Between Biopsy and Resection in Pleural Malignant Mesothelioma An International Multi-Institutional Analysis, AMERICAN JOURNAL OF CLINICAL PATHOLOGY, Vol: 156, Pages: 989-999, ISSN: 0002-9173
Popat S, Baas P, Faivre-Finn C, et al., 2021, Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up., Ann Oncol
Nicholson AG, Tsao MS, Beasley MB, et al., 2021, The 2021 WHO Classification of Lung Tumors: Impact of advances since 2015., J Thorac Oncol
The 2021 World Health Organisation (WHO) Classification of Thoracic Tumours was published earlier this year, with classification of lung tumors being one of the chapters. The principles remain those of using morphology first, supported by immunohistochemistry and then molecular techniques. In 2015, there was particular emphasis on using immunohistochemistry to make classification more accurate. In 2021, there is greater emphasis throughout the book on advances in molecular pathology across all tumor types. Major features within this edition are 1) broader emphasis on genetic testing than in the 2015 WHO Classification, 2) a chapter entirely dedicated to the classification of small diagnostic samples, 3) continued recommendation to document percentages of histological patterns in invasive non-mucinous adenocarcinomas, with utilization of these features to apply a formal grading system, as well as using only invasive size for T-factor size determination in part lepidic non-mucinous lung adenocarcinomas as recommended by the 8th Edition TNM Classification, 4) recognition of spread through airspaces (STAS) as a histological feature with prognostic significance, 5) moving lymphoepithelial carcinoma to squamous cell carcinomas, 6) update on evolving concepts in lung neuroendocrine neoplasm classification, 7) recognition of bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT) as a new entity within the adenoma subgroup, 8) recognition of thoracic SMARCA4-deficient undifferentiated tumor, and 9) inclusion of essential and desirable diagnostic criteria for each tumor.
Marx A, Chan JKC, Chalabreysse L, et al., 2021, The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: What Is New in Thymic Epithelial, Germ Cell, and Mesenchymal Tumors?, J Thorac Oncol
This overview of the fifth edition of the WHO classification of thymic epithelial tumors (including thymomas, thymic carcinomas, and thymic neuroendocrine tumors [NETs]), mediastinal germ cell tumors, and mesenchymal neoplasms aims to (1) list established and new tumor entities and subtypes and (2) focus on diagnostic, molecular, and conceptual advances since publication of the fourth edition in 2015. Diagnostic advances are best exemplified by the immunohistochemical characterization of adenocarcinomas and the recognition of genetic translocations in metaplastic thymomas, rare B2 and B3 thymomas, and hyalinizing clear cell carcinomas. Advancements at the molecular and tumor biological levels of utmost oncological relevance are the findings that thymomas and most thymic carcinomas lack currently targetable mutations, have an extraordinarily low tumor mutational burden, but typically have a programmed death-ligand 1high phenotype. Finally, data underpinning a conceptual advance are illustrated for the future classification of thymic NETs that may fit into the classification scheme of extrathoracic NETs. Endowed with updated clinical information and state-of-the-art positron emission tomography and computed tomography images, the fifth edition of the WHO classification of thymic epithelial tumors, germ cell tumors, and mesenchymal neoplasms with its wealth of new diagnostic and molecular insights will be a valuable source for pathologists, radiologists, surgeons, and oncologists alike. Therapeutic perspectives and research challenges will be addressed as well.
Nicholson AG, Moreira AL, Mino-Kenudson M, et al., 2021, Grading in Lung Adenocarcinoma: Another New Normal, RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY, Vol: 16, Pages: 1601-1604, ISSN: 1551-7411
Nastase A, Mandal A, Lu SK, et al., 2021, Integrated genomics point to immune vulnerabilities in pleural mesothelioma, Scientific Reports, Vol: 11, ISSN: 2045-2322
Pleural mesothelioma is an aggressive malignancy with limited effective therapies. In order to identify therapeutic targets, we integrated SNP genotyping, sequencing and transcriptomics from tumours and low-passage patient-derived cells. Previously unrecognised deletions of SUFU locus (10q24.32), observed in 21% of 118 tumours, resulted in disordered expression of transcripts from Hedgehog pathways and the T-cell synapse including VISTA. Co-deletion of Interferon Type I genes and CDKN2A was present in half of tumours and was a predictor of poor survival. We also found previously unrecognised deletions in RB1 in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary mesothelioma cells. Defects in Hippo pathways that included RASSF7 amplification and NF2 or LATS1/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin. Our results suggest new therapeutic avenues in mesothelioma and indicate targets and biomarkers for immunotherapy.
Bhatt R, Semple T, Slater O, et al., 2021, Extracorporeal membrane oxygenation: Bridging therapy in paediatric pulmonary Langerhans cell histiocytosis, JOURNAL OF PAEDIATRICS AND CHILD HEALTH, ISSN: 1034-4810
Lindsay CR, Shaw EC, Moore DA, et al., 2021, Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists, British Journal of Cancer, Vol: 125, Pages: 1210-1216, ISSN: 0007-0920
Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies.
Ravaglia C, Nicholson AG, 2021, Biopsy in interstitial lung disease: specific diagnosis and the identification of the progressive fibrotic phenotype, CURRENT OPINION IN PULMONARY MEDICINE, Vol: 27, Pages: 355-362, ISSN: 1070-5287
Pyae PK, Cama R, Nicholson AG, et al., 2021, Curious case of the unexplained exudative pleural effusion, BMJ CASE REPORTS, Vol: 14
Bui LT, Winters NI, Chung M-I, et al., 2021, Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity, NATURE COMMUNICATIONS, Vol: 12
Willis-Owen S, Domingo Sabugo C, Starren E, et al., 2021, Y disruption, autosomal hypomethylation and poor male lung cancer survival, Scientific Reports, Vol: 11, ISSN: 2045-2322
Lung cancer is the most frequent cause of cancer death worldwide. It affects more men than women, and men generally have worse survival outcomes. We compared gene co-expression networks in affected and unaffected lung tissue from 126 consecutive patients with Stage IA–IV lung cancer undergoing surgery with curative intent. We observed marked degradation of a sex-associated transcription network in tumour tissue. This disturbance, detected in 27.7% of male tumours in the discovery dataset and 27.3% of male tumours in a further 123-sample replication dataset, was coincident with partial losses of the Y chromosome and extensive autosomal DNA hypomethylation. Central to this network was the epigenetic modifier and regulator of sexually dimorphic gene expression, KDM5D. After accounting for prognostic and epidemiological covariates including stage and histology, male patients with tumour KDM5D deficiency showed a significantly increased risk of death (Hazard Ratio [HR] 3.80, 95% CI 1.40–10.3, P = 0.009). KDM5D deficiency was confirmed as a negative prognostic indicator in a further 1100 male lung tumours (HR 1.67, 95% CI 1.4–2.0, P = 1.2 × 10–10). Our findings identify tumour deficiency of KDM5D as a prognostic marker and credible mechanism underlying sex disparity in lung cancer.
Klebe S, Nakatani Y, Dobra K, et al., 2021, The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis, PATHOLOGY, Vol: 53, Pages: 446-453, ISSN: 0031-3025
Mino-Kenudson M, Le Stang N, Daigneault JB, et al., 2021, The International Association for the Study of Lung Cancer Global Survey on Programmed Death-Ligand 1 Testing for NSCLC, JOURNAL OF THORACIC ONCOLOGY, Vol: 16, Pages: 686-696, ISSN: 1556-0864
Abdelhady SG, Fouda EM, Shaheen MA, et al., 2021, Spectrum of childhood interstitial and diffuse lung diseases at a tertiary hospital in Egypt, ERJ OPEN RESEARCH, Vol: 7
Devaney R, Simpson T, Bush A, et al., 2021, Fructose 1,6-bisphosphatase deficiency as a cause of childhood interstitial lung disease, PEDIATRIC PULMONOLOGY, Vol: 56, Pages: 2362-2365, ISSN: 8755-6863
Johkoh T, Lee KS, Nishino M, et al., 2021, Chest CT Diagnosis and Clinical Management of Drug-related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors: A Position Paper from the Fleischner Society, RADIOLOGY, Vol: 298, Pages: 550-566, ISSN: 0033-8419
Johkoh T, Lee KS, Nishino M, et al., 2021, Chest CT Diagnosis and Clinical Management of Drug-Related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors A Position Paper From the Fleischner Society, CHEST, Vol: 159, Pages: 1107-1125, ISSN: 0012-3692
Salguero FJ, White AD, Slack GS, et al., 2021, Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19, NATURE COMMUNICATIONS, Vol: 12
Invernizzi R, Wu BG, Barnett J, et al., 2021, The respiratory microbiome in chronic hypersensitivity pneumonitis is distinct from that of idiopathic pulmonary fibrosis, American Journal of Respiratory and Critical Care Medicine, Vol: 203, Pages: 339-347, ISSN: 1073-449X
RATIONALE: Chronic hypersensitivity pneumonitis (CHP) is a condition that arises following repeated exposure and sensitisation to inhaled antigens. The lung microbiome is increasingly implicated in respiratory disease but to date, no study has investigated the composition of microbial communities in the lower airways in CHP. OBJECTIVE: To characterise and compare the airway microbiome in subjects with CHP, idiopathic pulmonary fibrosis (IPF) and controls. METHODS: We prospectively recruited individuals diagnosed with CHP (n=110), IPF (n=45) and controls (n=28). Subjects underwent bronchoalveolar lavage and bacterial DNA was isolated, quantified by qPCR and the 16S rRNA gene was sequenced to characterise the bacterial communities in the lower airways. MAIN MEASUREMENTS AND RESULTS: Distinct differences in the microbial profiles were evident in the lower airways of subjects with CHP and IPF. At the phylum level, the prevailing microbiota of both IPF and CHP subjects included Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria. However, in IPF, Firmicutes dominated while the percentage of reads assigned to Proteobacteria in the same group was significantly lower compared to CHP subjects. At the genus level, Staphylococcus was increased in CHP and Actinomyces and Veillonella in IPF. The lower airway bacterial burden in CHP subjects was higher than controls but lower than those with IPF. In contrast to IPF, there was no association between bacterial burden and survival in CHP. CONCLUSIONS: The microbial profile of the lower airways in subjects with CHP is distinct from that of IPF and, notably, bacterial burden in individuals with CHP fails to predict survival.
Chua F, Bartlett E, Barnett J, et al., 2021, PLEUROPARENCHYMAL FIBROELASTOSIS: CLINICAL, FUNCTIONAL AND MORPHOLOGIC DETERMINANTS OF MORTALITY, Publisher: BMJ PUBLISHING GROUP, Pages: A74-A74, ISSN: 0040-6376
Popat S, Sharma B, MacMahon S, et al., 2021, Durable Response to Vismodegib in PTCH1 F1147fs Mutant Relapsed Malignant Pleural Mesothelioma: Implications for Mesothelioma Drug Treatment, JCO PRECISION ONCOLOGY, Vol: 5, Pages: 39-43
Bui LT, Winters NI, Chung M-I, et al., 2021, Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity., bioRxiv
Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyzed the transcriptomes of 605,904 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observed a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD epithelial cells expressed higher levels of genes linked directly to the efficiency of viral replication and innate immune response. Additionally, we identified basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.
Raghu G, Remy-Jardin M, Ryerson CJ, et al., 2021, Diagnosis of Hypersensitivity Pneumonitis in Adults: An Official ATS/JRS/ALAT Clinical Practice Guideline (vol 202, pg e36, 2020), AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 203, Pages: 150-151, ISSN: 1073-449X
Barnett J, Pulzato I, Javed M, et al., 2021, Radiological-pathological correlation of negative CT biopsy results enables high negative predictive value for thoracic malignancy, CLINICAL RADIOLOGY, Vol: 76, ISSN: 0009-9260
Cui W, Yousaf N, Bhosle J, et al., 2020, Real-world outcomes in thoracic cancer patients with severe Acute respiratory syndrome Coronavirus 2 (COVID-19): Single UK institution experience, Cancer Treatment and Research Communications, Vol: 25, Pages: 100261-100261, ISSN: 2468-2942
BACKGROUND: UK COVID-19 mortality rates are amongst the highest globally. Controversy exists on the vulnerability of thoracic cancer patients. We describe the characteristics and sequelae of patients with thoracic cancer treated at a UK cancer centre infected with COVID-19. METHODS: Patients undergoing care for thoracic cancer diagnosed with COVID-19 (RT-PCR/radiology/clinically) between March-June 2020 were included. Data were extracted from patient records. RESULTS: Thirty-two patients were included: 14 (43%) diagnosed by RT-PCR, 18 (57%) by radiology and/or convincing symptoms. 88% had advanced thoracic malignancies. Eleven of 14 (79%) patients diagnosed by RT-PCR and 12 of 18 (56%) patients diagnosed by radiology/clinically were hospitalised, of which four (29%) and 2 (11%) patients required high-dependency/intensive care respectively. Three (21%) patients diagnosed by RT-PCR and 2 (11%) patients diagnosed by radiology/clinically required non-invasive ventilation; none were intubated. Complications included pneumonia and sepsis (43% and 14% respectively in patients diagnosed by RT-PCR; 17% and 11% respectively in patients diagnosed by radiology/clinically). In patients receiving active cancer treatment, therapy was delayed/ceased in 10/12 (83%) and 7/11 (64%) patients diagnosed by RT-PCR and radiology/clinically respectively. Nine (28%) patients died; all were smokers. Median time from symptom onset to death was 7 days (range 3-37). CONCLUSIONS: The immediate morbidity from COVID-19 is high in thoracic cancer patients. Hospitalisation and treatment interruption rates were high. Improved risk-stratification models for UK cancer patients are urgently needed to guide safe cancer-care delivery without compromising efficacy.
Domingo-Sabugo C, Starren E, Mandal A, et al., 2020, Distinct Landscapes of Genomic Alterations between Lung Carcinoids and Non-Small Cell Lung Cancers, Publisher: SPRINGERNATURE, Pages: 528-528, ISSN: 1018-4813
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