Publications
664 results found
Khiroya R, Macaluso C, Montero MA, et al., 2017, Pleuroparenchymal Fibroelastosis: A Review of Histopathologic Features and the Relationship Between Histologic Parameters and Survival., American Journal of Surgical Pathology, Vol: 41, Pages: 1683-1689, ISSN: 0147-5185
Pleuroparenchymal fibroelastosis (PPFE) is now a defined clinicopathologic entity in the updated 2013 ATS/ERS classification of idiopathic interstitial pneumonias (IIPs), which has led to a significant increase in cases being diagnosed at our institution. We have therefore reviewed 43 PPFE cases (58 biopsies in total) to assess whether any clinical or histopathologic features provide prognostic information. A semiquantatitive grading system was used to assess extent of fibroblastic foci, intra-alveolar fibroelastosis, visceral pleural fibrosis, chronic inflammation in areas of fibrosis, vascular fibrointimal thickening, and presence of granulomas. Other patterns of interstitial lung disease were also noted, if present. All biopsies showed intra-alveolar fibroelastosis, fibroblastic foci at the leading edge of fibrosis and chronic inflammation within areas of fibrosis, 91% showed vascular fibrointimal thickening of vessels, 73% showed pleural fibrosis, and 35% showed granulomas. Ten cases showed a coexistent IIP (5 usual IIP, 5 showed features of hypersensitivity pneumonitis). There was no significant correlation with mortality and severity of histologic parameters, other than a significant decrease in mortality in PPFE with coexistent granulomas, after adjusting for age and gender (hazard ratio, 0.27; P=0.049). Male gender was also associated with an increased risk of mortality, after adjusting for age (hazard ratio, 4.8; P=0.045). PPFE is more common than previously thought, not infrequently showing coexistent pathology, specifically usual interstitial pneumonia and granulomatous lung disease, our data suggesting the latter may have prognostic significance.
Nicholson AG, 2017, UIP, NSIP and Their Differential Diagnoses, 10th Joint Meeting of the British-Division of the International-Academy-of-Pathology and the Pathological-Society-of-Great-Britain-and-Ireland, Publisher: WILEY, Pages: S4-S4, ISSN: 0022-3417
Jacob J, Bartholmai BJ, Rajagopalan S, et al., 2017, Unclassifiable-interstitial lung disease: Outcome prediction using CT and functional indices, RESPIRATORY MEDICINE, Vol: 130, Pages: 43-51, ISSN: 0954-6111
BackgroundUnclassifiable-interstitial lung disease (uILD) represents a heterogeneous collection of pathologies encompassing those fibrosing lung diseases which do not fulfill current diagnostic criteria. We evaluated baseline and longitudinal functional and CT (visual and quantitative computer [CALIPER] analysis) variables to identify outcome predictors in uILD.MethodsConsecutive patients with uILD on multidisciplinary review (n = 95) had baseline functional (FVC, DLco, CPI [composite physiologic index]) and CT features (visual evaluation: CT pattern, fibrosis extent, honeycombing presence, traction bronchiectasis severity, pulmonary artery (PA) diameter; CALIPER evaluation: fibrosis extent, pulmonary vessel volume (PVV)) examined in univariate and multivariate Cox regression models. Change in functional and CT variables were examined in a patient subset (n = 37), to identify indicators of outcome.ResultsOn univariate analysis, CPI was the most powerful functional predictor of mortality (p < 0.0001). Visual traction bronchiectasis (p < 0.0001), PA diameter (p < 0.0001) and honeycombing presence (p = 0.0001) and CALIPER PVV (p = 0.0003) were the strongest CT outcome predictors.On multivariate analysis of baseline indices, traction bronchiectasis (p = 0.003), PA diameter (p = 0.003) and CPI (p = 0.0001) independently predicted mortality. Colinearity with functional indices precluded the evaluation of CALIPER PVV in multivariate models.On evaluation of longitudinal variables, increasing CALIPER fibrosis extent was the strongest outcome predictor, and remained so following adjustment for baseline disease severity, and when FVC declines were marginal.ConclusionsIn uILD patients, CPI, traction bronchiectasis severity and PA diameter independently predicted outcome at baseline. Increasing fibrosis extent measured by CALIPER was the most powerful index of outcome regardless of baseline disease severity and strongly predicted outcome in patients with marginal FVC de
Tokaca N, Wotherspoon A, Nicholson AG, et al., 2017, Lack of response to nivolumab in a patient with EGFR-mutant non-small cell lung cancer adenocarcinoma sub-type transformed to small cell lung cancer, Lung Cancer, Vol: 111, Pages: 65-68, ISSN: 0169-5002
Small cell transformation is a rare but well recognised mechanism of acquired resistance to EGFR-TKI therapy in EGFR-mutated NSCLC, but optimal drug therapy thereof is unknown. Nivolumab has demonstrated activity in relapsed de novo small cell lung cancer in early phase trials. Here, we report a case of transformed EGFR-mutant SCLC treated with nivolumab with no benefit.
Egashira R, Jacob J, Kokosi MA, et al., 2017, Diffuse Pulmonary Ossification in Fibrosing Interstitial Lung Diseases: Prevalence and Associations, Radiology, Vol: 284, Pages: 255-263, ISSN: 0033-8419
PurposeTo investigate the prevalence of diffuse pulmonary ossification (DPO) in patients with fibrosing interstitial lung disease (ILD) and determine whether there are differences among the types of ILDs.Materials and MethodsInstitutional review board approval was given and patient consent was not required for this study. The study population comprised 892 consecutive patients with fibrosing ILD, including 456 patients with idiopathic pulmonary fibrosis (IPF) (men, 366; women, 90; median age, 72 years [range, 38–93 years]), 244 with nonspecific interstitial pneumonia (men, 79; women, 165; median age, 60.5 years [range, 23–86 years]), and 192 with chronic hypersensitivity pneumonitis (men, 76; women, 116; median age, 66 years [range, 35–88 years]). Pulmonary ossifications were recorded when nodules (<4 mm diameter) were identified on bone window images (width, 2500 HU; level, 500 HU). DPO was defined as 10 or more bilateral nodular ossifications (definition 1) or as one or more lobes with five or more bilateral nodular ossifications (definition 2). Relationships among pulmonary ossification and parenchymal patterns, clinical parameters, and multidisciplinary team diagnoses were examined. The prevalence of DPO was compared with the χ2 statistic or Fisher exact test, and multivariate analysis was performed with logistic regression.ResultsIn the whole population, the prevalence of DPO was 166 (18.6%) and 106 (11.9%) of 892 patients according to definitions 1 and 2, respectively. The prevalence of DPO (definition 1) was significantly higher in patients with IPF (28.5%) than in those without IPF (8.3%, P < .001). Nine of 192 (4.7%) had chronic hypersensitivity pneumonitis (P < .001), and 27 of 244 (11.1%) had nonspecific interstitial pneumonia (P < .001). At multivariate analysis, DPO according to definition 1 was an independent predictor of IPF diagnosis (P < .001) and male sex (P = .003). Coarseness of fibrosing ILD (P = .011) and IP
Abbosh C, Birkbak NJ, Wilson GA, et al., 2017, Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution, NATURE, Vol: 545, Pages: 446-451, ISSN: 0028-0836
The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.
Chansky K, Detterbeck FC, Nicholson AG, et al., 2017, The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer, JOURNAL OF THORACIC ONCOLOGY, Vol: 12, Pages: 1109-1121, ISSN: 1556-0864
Hind M, Jordan S, Hansell DM, et al., 2017, A man with progressive type II respiratory failure, Lancet Respiratory Medicine, Vol: 5, Pages: 456-456, ISSN: 2213-2600
Goh NS, Hoyles RK, Denton CP, et al., 2017, Short term pulmonary function trends are predictive of mortality in interstitial lung disease associated with systemic sclerosis., Arthritis & Rheumatology, Vol: 69, Pages: 1670-1678, ISSN: 2326-5191
OBJECTIVE: To determine the prognostic value of pulmonary function test (PFT) trends at one and two years in interstitial lung disease associated with systemic sclerosis (SSc-ILD). METHODS: The prognostic significance of PFT trends at one year (n=162), and two years (n=140) was examined against 15 year survival. PFT trends, expressed as continuous and categorical change in separate analyses, were examined against mortality in univariate and multivariate models. SSc-ILD was defined at presentation as limited lung fibrosis or extensive lung fibrosis using the UKRSA staging system. RESULTS: One year PFT trends were predictive of mortality only in patients with extensive lung fibrosis: categorical FVC change, alone or in combination with categorical change in DLco, had greater prognostic significance than continuous FVC change or trends in other PFT variables. Taking into account both prognostic value and sensitivity to change, the optimal definition of progression for trial purposes was an FVC and DLco composite, consisting of either an FVC decline from baseline ≥10% or an FVC decline of 5-9% in association with a DLco decline of ≥15%. At two years, gas transfer trends had the greatest prognostic significance, in the whole cohort and in limited lung fibrosis. However, in extensive lung fibrosis, the composite end-point defined above was the strongest prognostic determinant. Larger changes were required in the FVC/DLco ratio than in Kco to achieve prognostic significance. CONCLUSION: Our findings provide support for routine spirometric and gas transfer monitoring in SSc-ILD, based on linkages to long-term outcome, with further evaluation of a composite FVC and DLco end-point warranted for trial purposes. This article is protected by copyright. All rights reserved.
Macedo P, Zhang Q, Saito J, et al., 2017, Analysis of bronchial biopsies in chronic cough, RESPIRATORY MEDICINE, Vol: 127, Pages: 40-44, ISSN: 0954-6111
Hurst JR, Verma N, Lowe D, et al., 2017, British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders., Journal of Allergy and Clinical Immunology: In Practice, Vol: 5, Pages: 938-945, ISSN: 2213-2198
A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51).
Khiroya R, Montero MA, Rice A, et al., 2017, Pleuroparenchymal Fibroelastosis: A Review of Histopathological Features, JOURNAL OF PATHOLOGY, Vol: 241, Pages: S7-S7, ISSN: 0022-3417
Jacob J, Nicholson AG, Wells AU, et al., 2017, Impact of pulmonary vascular volume on mortality in IPF: is it time to reconsider the role of vasculature in disease pathogenesis and progression?, EUROPEAN RESPIRATORY JOURNAL, Vol: 49, ISSN: 0903-1936
Jacob J, Nicholson AG, Wells AU, et al., 2017, Impact of pulmonary vascular volume on mortality in IPF: is it time to reconsider the role of vasculature in disease pathogenesis and progression?, EUROPEAN RESPIRATORY JOURNAL, Vol: 49, ISSN: 0903-1936
Zainun K, Hope K, Nicholson AG, et al., 2017, Abnormal Muscularization of Intra-acinar Pulmonary Arteries in Two Cases Presenting as Sudden Infant Death, PEDIATRIC AND DEVELOPMENTAL PATHOLOGY, Vol: 20, Pages: 49-53, ISSN: 1093-5266
Montero MA, Osadolor T, Khiroya R, et al., 2017, Restrictive allograft syndrome and idiopathic pleuroparenchymal fibroelastosis: do they really have the same histology?, HISTOPATHOLOGY, Vol: 70, Pages: 1107-1113, ISSN: 0309-0167
Fraccaro A, Montero-Fernandez A, Nicholson AG, et al., 2017, Tissue Expression Of Th2 Markers: Comparison Between Idiopathic Pulmonary Fibrosis And Fibrotic Hypersensitivity Pneumonitis, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Chudasama D, Barr J, Beeson J, et al., 2017, Detection of Circulating Tumour Cells and Survival of Patients with Non-small Cell Lung Cancer, ANTICANCER RESEARCH, Vol: 37, Pages: 169-173, ISSN: 0250-7005
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- Citations: 24
Gennatas S, Lu SK, Anbunathan H, et al., 2017, Somatic BAP1 and NF2 mutations in pleural malignant mesothelioma and their correlation with clinical phenotype
Gennatas S, Anbunathan H, Bowman A, et al., 2017, Somatic and germline mutations in thymic epithelial tumours and their correlation with histological and clinical phenotypes
Leung M, Ryan D, Hulme R, et al., 2017, Defining molecular residual disease after lung cancer resection, LUNG CANCER, Vol: 103, Pages: S72-S73, ISSN: 0169-5002
Thunnissen E, Borczuk AC, Flieder DB, et al., 2016, The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases, JOURNAL OF THORACIC ONCOLOGY, Vol: 12, Pages: 334-346, ISSN: 1556-0864
Chudasama DY, Freydina DV, Freidin MB, et al., 2016, Inertia based microfluidic capture and characterisation of circulating tumour cells for the diagnosis of lung cancer, ANNALS OF TRANSLATIONAL MEDICINE, Vol: 4, ISSN: 2305-5839
Shah PL, Kemp SV, Newton RC, et al., 2016, Clinical Correlation between Real-Time Endocytoscopy, Confocal Endomicroscopy, and Histopathology in the Central Airways, RESPIRATION, Vol: 93, Pages: 51-57, ISSN: 0025-7931
Nicholson AG, 2016, Evolution of Classifications in Lung Pathology, 9th Joint Meeting of the British-Division of the International-Academy-of-Pathology and the Pathological-Society-of-Great-Britain-and-Ireland, Publisher: WILEY-BLACKWELL, Pages: 5-5, ISSN: 0022-3417
Nicholson AG, Detterbeck F, Marx A, et al., 2016, Dataset for reporting of thymic epithelial tumours: recommendations from the International Collaboration on Cancer Reporting (ICCR), HISTOPATHOLOGY, Vol: 70, Pages: 522-538, ISSN: 0309-0167
Russell A, 2016, Interstitial Lung disease, Respiratory Nursing at a Glance, Publisher: John Wiley & Sons, ISBN: 9781119048305
Provides need-to-know information in a highly visual, evidence-based, quick-reference format. Respiratory Nursing at a Glance is ideal for nurses and health care students and practitioners at all levels involved in respiratory care.
George PM, Devaraj A, Nicholson AG, et al., 2016, Interactive grand round at The Royal Brompton Hospital: Emerging Interstitial Lung Disease, Publisher: Elsevier: Lancet
George PM, Devaraj A, Nicholson AG, et al., 2016, An emerging interstitial lung disease., Lancet Respiratory Medicine, Vol: 4, Pages: 762-762, ISSN: 2213-2619
Khairul Z, Kirsten H, Nicholson AG, et al., 2016, Abnormal muscularization of intra acinar pulmonary arteries in two cases presenting as Sudden Infant Death (SIDS)., Pediatric and Developmental Pathology, ISSN: 1615-5742
Abnormal muscularization of intra acinar pulmonary arteries is a histological hallmark of persistent pulmonary hypertension of newborn (PPHN), an uncommon disease with high morbidity and mortality. PPHN presents with signs of respiratory distress immediately following birth. The disease is multi-factorial in origin and can be idiopathic as well associated with a variety of conditions such as congenital heart disease and both congenital and acquired lung diseases. We report two cases presenting as sudden unexpected death in late neonatal period (SUDI) showing abnormal muscularization of acinar pulmonary arteries reminiscent of PPHN. The significance of this report is twofold; to increase the awareness amongst pediatricians and pathologists of this feature not previously described in SUDI/Sudden Infant Death Syndrome (SIDS) and to highlight the importance of performing a thorough autopsy in order to identify the diagnosis.
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