Publications by authors named "John C English"

Appropriate management requires timely and accurate confirmation of non-small cell lung cancer (NSCLC) recurrence in patients who have had curative-intent surgical resection. We assessed the association between circulating tumor DNA (ctDNA) identified using amplicon sequencing and evidence of recurrence on CT surveillance. A prospective cohort study of NSCLC patients with early-stage disease undergoing curative-intent resection was conducted.

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The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training.

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Lung transplantation is a life-saving treatment for patients with end-stage lung disease. COVID-19 has been associated with a severe and rapid decline in pulmonary function, in which case lung transplantation has been described to be effective. We herein describe 9 patients who underwent lung transplantation for COVID-19 acute respiratory distress syndrome, of whom 6 were bridged with extracorporeal membrane oxygenation (ECMO).

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Context.—: The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability.

Objective.

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Background: Despite meticulous surgery for non-small cell lung cancer (NSCLC), relapse is as high as 70% at 5 years. Many institutions do not conduct reflexive molecular testing on early stage specimens, although targeted gene therapy may extend life by years in the event of recurrence. This ultimately delays definitive treatment with additional biopsy risking suboptimal tissue acquisition and quality for molecular testing.

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Purpose: Primary lung cancers associated with cystic airspaces are increasingly being recognized; however, there is a paucity of data on their natural history. We aimed to evaluate the prevalence, pathologic, and imaging characteristics of cystic lung cancer in a regional thoracic surgery center with a focus on the evolution of computed tomography morphology over time.

Materials And Methods: Consecutive patients referred for potential surgical management of primary lung cancer between January 2016 and December 2018 were included.

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Chronic lung allograft dysfunction (CLAD) is the most common cause of mortality in lung transplant recipients after the 1st year of transplantation. CLAD has traditionally been classified into two distinct obstructive and restrictive forms: bronchiolitis obliterans syndrome and restrictive allograft syndrome. However, CLAD may manifest with a spectrum of imaging and pathologic findings and a combination of obstructive and restrictive physiologic abnormalities.

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Objectives: The majority of coronavirus disease 2019 mortality and morbidity is attributable to respiratory failure from severe acute respiratory syndrome coronavirus 2 infection. The pathogenesis underpinning coronavirus disease 2019-induced respiratory failure may be attributable to a dysregulated host immune response. Our objective was to investigate the pathophysiological relationship between proinflammatory cytokines and respiratory failure in severe coronavirus disease 2019.

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Introduction: The 2011 IASLC classification system proposes guidelines for radiologists and pathologists to classify adenocarcinomas spectrum lesions as preinvasive, minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA). IA portends the worst clinical prognosis, and the imaging distinction between MIA and IA is controversial.

Materials And Methods: Subsolid pulmonary nodules resected by microcoil localization over a three-year period were retrospectively reviewed by three chest radiologists and a pulmonary pathologist.

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The testicular spread of renal cell carcinoma is extremely rare. Five cases of renal cell carcinoma metastatic to the testis are described. The patients ranged from 45 to 81 years of age.

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Gene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity.

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Background: Gaucher disease type 1 (GD1) is a lysosomal storage disease rarely resulting in end stage pulmonary hypertension (PH) and interstitial lung disease. There have only been two previous case reports of patients with GD1 receiving lung transplants.

Case Presentation: We report a case of successful bilateral sequential lung transplantation in a patient with end-stage GD1-related PH.

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Background: The tumor microenvironment (TME) is a complex mixture of tumor epithelium, stroma and immune cells, and the immune component of the TME is highly prognostic for tumor progression and patient outcome. In lung cancer, anti-PD-1 therapy significantly improves patient survival through activation of T cell cytotoxicity against tumor cells. Direct contact between CD8+ T cells and target cells is necessary for CD8+ T cell activity, indicating that spatial organization of immune cells within the TME reflects a critical process in anti-tumor immunity.

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Rationale: The interstitial lung disease (ILD) specialists in Vancouver participate in a multidisciplinary discussion (MDD) that is primarily used internally for patients seen by these specialists. The MDD is also used remotely (externally) by general pulmonologists to increase access to this service.

Objectives: To describe the impact of an MDD on the diagnosis and management of ILD in these two patient cohorts, and to report the satisfaction of referring pulmonologists with this service.

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Background: Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer.

Methods: We did this single-arm, prospective study in eight centres across Canada.

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Introduction: Lung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited.

Methods: Participants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk-selected in Canada.

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Diffuse pulmonary ossification (DPO) is a rare disease with unknown pathogenesis, clinical manifestations, and treatment options. This report describes the diagnosis of DPO in an otherwise healthy 26-year-old man with recurrent spontaneous pneumothorax. His father was diagnosed with a similar lung condition in his 30's with computed tomography (CT) images that were strikingly similar to those of the patient.

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Lung cancer is a leading cause of cancer-related deaths worldwide. Lung cancer risk factors, including smoking and exposure to environmental carcinogens, have been linked to chronic inflammation. An integral feature of inflammation is the activation, expansion and infiltration of diverse immune cell types, including CD4 T cells.

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Context: - The histopathologic criteria for idiopathic pulmonary fibrosis were revised in the American Thoracic Society/European Respiratory Society/Japan Respiratory Society/Latin American Thoracic Association guidelines in 2011. However, the evidence of diagnosis based on the guidelines needs further investigation.

Objective: - To examine whether the revised histopathologic criteria for idiopathic pulmonary fibrosis improved interobserver agreement among pathologists and the predicted prognosis in patients with interstitial pneumonia.

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Genes involved in fetal lung development are thought to play crucial roles in the malignant transformation of adult lung cells. Consequently, the study of lung tumour biology in the context of lung development has the potential to reveal key developmentally relevant genes that play critical roles in lung cancer initiation/progression. Here, we describe for the first time a comprehensive characterization of miRNA expression in human fetal lung tissue, with subsequent identification of 37 miRNAs in non-small cell lung cancer (NSCLC) that recapitulate their fetal expression patterns.

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Pleuroparenchymal fibroelastosis (PPFE) is a newly described form of interstitial lung disease that originates in the upper lung zones and typically progresses to involve the entire lung. The disease may be idiopathic but is often associated with other pre- or coexisting conditions. Pneumothorax is a common complication and can occur at presentation or at other times during the course of the disease.

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Background: Cigarette smoke is associated with the majority of lung cancers: however, 25% of lung cancer patients are non-smokers, and half of all newly diagnosed lung cancer patients are former smokers. Lung tumors exhibit distinct epidemiological, clinical, pathological, and molecular features depending on smoking status, suggesting divergent mechanisms underlie tumorigenesis in smokers and non-smokers. MicroRNAs (miRNAs) are integral contributors to tumorigenesis and mediate biological responses to smoking.

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Background: It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs.

Methods: Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT).

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Background: An imbalance between proteolytic enzymes and their inhibitors is thought to be involved in the pathogenesis of chronic obstructive pulmonary disease. Matrix metalloproteinase-1, also known as interstitial collagenase, has been implicated as a potentially important proteinase in the genesis of chronic obstructive pulmonary disease and, more specifically, emphysema.

Methods: We performed quantitative immunohistochemical assessment of matrix metalloproteinase-1 expression in the resected lung of 20 smokers/ex-smokers who had varying severity of airflow obstruction and emphysema and compared this with the lungs of 5 nonsmokers.

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