Andrew G Nicholson

VU University Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (378)2407.87 Total impact

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    ABSTRACT: Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50-90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene-liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1-7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in efficacy and consistency of response to the current formulation are needed before gene therapy is suitable for clinical care; however, our findings should also encourage the rapid introduction of more potent gene transfer vectors into early phase trials. Medical Research Council/National Institute for Health Research Efficacy and Mechanism Evaluation Programme. Copyright © 2015 Alton et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
    07/2015; DOI:10.1016/S2213-2600(15)00245-3
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    ABSTRACT: Interstitial lung disease in children (chILD) is rare, and most centres will only see a few cases/year. There are numerous possible underlying diagnoses, with specific and non-specific treatment possibilities. The chILD-EU collaboration has brought together centres from across Europe to advance understanding of these considerations, and as part of this process, has created standard operating procedures and protocols for the investigation of chILD. Where established consensus documents exist already, for example, for the performance of bronchoalveolar lavage and processing of lung biopsies, these have been adopted. This manuscript reports our proposals for a staged investigation of chILD, starting from when the condition is suspected to defining the diagnosis, using pathways dependent on the clinical condition and the degree of illness of the child. These include the performance of genetic testing, echocardiography, high-resolution CT, bronchoscopy when appropriate and the definitive investigation of lung biopsy, in order to establish a precise diagnosis. Since no randomised controlled trials of treatment have ever been performed, we also report a Delphi consensus process to try to harmonise treatment protocols such as the use of intravenous and oral corticosteroids, and add-on therapies such as hydroxychloroquine and azithromycin. The aim is not to dictate to clinicians when a therapeutic trial should be performed, but to offer the possibility to collaborators of having a unified approach when a decision to treat has been made. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Thorax 07/2015; DOI:10.1136/thoraxjnl-2015-207349 · 8.56 Impact Factor
  • Khin Thway, Simon Jordan, Cyril Fisher, Andrew G Nicholson
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    ABSTRACT: Primary intrathoracic sarcomas are a rare, heterogeneous group of neoplasms that occur in the lung parenchyma, pleura and mediastinum. Although pathologically diverse, they frequently exhibit similar clinical and radiologic features, and hence accurate histopathological diagnosis is crucial for correct management and prognostication. The characterisation of sarcomas can be difficult as there is frequent overlap between the histological patterns of benign and malignant lesions, and between different malignant tumours and with non-mesenchymal neoplasms. This is particularly critical within the thorax, where many spindle cell neoplasms represent tumours of epithelial origin or metastatic disease. Immunohistochemistry and molecular genetic techniques are important ancillary contributors to histological interpretation, but several groups of tumours still lack reliable immunohistochemical markers or reproducible genetic changes. We review the pathology of the major types of intrathoracic sarcomas with reference to clinical factors, morphology, immunohistochemistry, and molecular genetics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Histopathology 07/2015; DOI:10.1111/his.12771 · 3.30 Impact Factor
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    ABSTRACT: Circulating tumour cells (CTCs) attract a significant interest both in basic cancer research and in clinical oncology as a biomarker for diagnosis and prognosis of cancer. A number of techniques have been developed to trap and visualise CTCs.1 We postulated that antibody-independent approaches for collection of CTCs have a number of advantages, although subsequent effective visualisation of CTCs to distinguish them from surrounding white blood cells or non-cancerous epithelial cells is critical for their applicability for use in standard clinical settings.2 ,3 One potential solution is the usage of sensitive staining techniques such as recently developed ViewRNA in situ hybridisation by Affymetrix/Panomics. This approach is based on the use of specifically designed oligonucleotide probes against mRNA of genes of interest. These probes are hybridised to mRNA in fixed cells followed by binding of branched nucleic acids and fluorescent or chromogenic staining, which allow simultaneous identification of two or three targets, … [Full text of this article]
    Journal of clinical pathology 05/2015; DOI:10.1136/jclinpath-2015-203112 · 2.55 Impact Factor
  • WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart., 4 edited by Travis W.D., Brambilla E., Burke A.P., Marx A., Nicholson A. G., 04/2015: chapter Adenocarcinoma; IARC Press., ISBN: 9789283224365
  • WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart., 4 edited by Travis W.D., Brambilla E., Burke A.P., Marx A., Nicholson A. G., 04/2015: chapter Variants of invasive adenocarcinoma; IARC Press., ISBN: 9789283224365
  • WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart., 4 edited by Travis W.D., Brambilla E., Burke A.P., Marx A., Nicholson A. G., 04/2015: chapter Minimally invasive adenocarcinoma; IARC Press., ISBN: 9789283224365
  • WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart., Edited by Travis W.D., Brambilla E., Burke A.P., Marx A., Nicholson A. G., 04/2015: chapter Preinvasive lesions; IARC Press., ISBN: 9789283224365
  • Eric Lim, Andrew G Nicholson, Simon Padley, Sanjay Popat
    04/2015; 3(4):328. DOI:10.1016/S2213-2600(15)00035-1
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    ABSTRACT: Therapeutic antibodies to Programmed Death receptor 1 (PD-1) and it's ligand PD-L1 show promising clinical results. Anti-PD-L1 immunohistochemistry (IHC) may be a biomarker to select patients more likely to respond to these treatments. However, the development of at least four different therapeutics, each with a different anti-PD-L1 IHC assay, has raised concerns amongst pathologists and oncologists alike. This paper reviews existing data on the IHC biomarker aspects of studies using these drugs in non-small cell carcinoma (NSCLC) and considers the challenges ahead, should these drug/IHC assay combinations reach routine practice. For each the known biomarker assays in development, there is a different monoclonal IHC antibody clone, produced by one of two diagnostics companies. Each test requires proprietary staining platforms and uses different definitions of a 'positive' test for PD-L1 expression, on tumour cells and, in one test, also on tumour infiltrating immune cells. There are still considerable gaps in our knowledge of the technical aspects of these tests, as well as of the biological implications and associations of PD-L1 expression in NSCLC, considering heterogeneity of expression, dynamic changes in expression and prognostic implications amongst other factors. The IASLC Pathology Committee raises the prospect of trying to harmonize and standardize testing for PD-L1 by IHC, at least at a technical level, but also, ideally, as a predictive marker, in order to facilitate availability of this test and a promising treatment for patients with NSCLC.
    Journal of Thoracic Oncology 03/2015; DOI:10.1097/JTO.0000000000000526 · 5.80 Impact Factor
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    ABSTRACT: To review the clinical features of nine patients with pulmonary light-chain deposition disease (LCDD) and record their high-resolution CT (HRCT) and histopathological findings. Patients with a diagnosis of LCDD on lung biopsy specimen were retrospectively identified. The HRCT characteristics of nodules, cysts, and ancillary findings; change at follow-up; and histopathological findings were documented. Features common to all nine cases were thin-walled cysts. In seven cases, vessels traversing the cysts were identified. The majority of patients (8/9) had at least one pulmonary nodule. There was no zonal predominance of either cysts or nodules. The disease appeared stable in the majority of cases with no serial change in HRCT appearances (5/6 cases with follow-up data, mean duration 29 months). To the authors' knowledge, this is the largest series of pulmonary LCDD patients in the literature, and the first systematic assessment of HRCT findings. Pulmonary cysts are a unifying feature, usually with pulmonary nodules, and serial change on HRCT is unusual. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
    Clinical Radiology 02/2015; 70(5). DOI:10.1016/j.crad.2015.01.002 · 1.66 Impact Factor
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    ABSTRACT: The rarity of thymomas and lack of multi-institutional studies have hampered therapeutic progress for decades. To overcome this, the members of the International Thymic Malignancy Interest Group created a worldwide retrospective database. This database was analyzed regarding the demographic and geographic distribution of thymomas and the impact of different variables on survival and recurrence. This study analyzed 4221 thymomas diagnosed between 1983 and 2012 with World Health Organization histotype information from the International Thymic Malignancy Interest Group database. Associations to survival and recurrence were studied by univariate and multivariate analyses. Type B2 thymoma is the most common (28%) and type A the least common (12%) histotypes. They are significantly more frequent in Europe and the United States than Asia. Type A and AB occur at significantly higher age than other thymomas (64 and 57 years, respectively). There are no differences in gender distribution. Stage is lower in type A (90% in stages I-II) and AB than B1 to B3 thymomas (38% of type B3 in stage III). In univariate analysis, recurrence is significantly less frequent among stage I/II tumors, in type A and AB (recurrence rates, 1-2%) than B1 to B3 thymomas (2-7%). Multivariate analysis reveals an impact of age, stage, and resection status on survival and recurrence, whereas for histology there is only a significant impact on recurrence. New findings are (1) geographic differences such as a lower incidence of type A and B2 thymoma in Asia; and (2) impact of stage and histology, the latter partially limited to early stage disease, on recurrence.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2015; 10(2):367-372. DOI:10.1097/JTO.0000000000000393 · 5.80 Impact Factor
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    ABSTRACT: We have analyzed levels of bombesin-positive neuroendocrine cells (NECs) in neuroendocrine cell hyperplasia of infancy (NEHI) and other childhood interstitial lung diseases (chILDs) in order to validate proposed histological criteria for NEHI and investigate its etiology. The extent of bombesin-positive cells within airway epithelium was analyzed in lung biopsies from 7 patients diagnosed with NEHI, including two previously classified as non-diagnostic, and other chILDs (n=64) with age range 1 month to 18 years. NECs were counted and calculated as a percentage of airways containing NECs, average percentage of NECs per airway, percentage of airways with >10% NECs and number of neuroendocrine bodies (NEBs). Correlation with age and gender was also undertaken. Patients with NEHI had the highest average percentage of bombesin-positive NECs per airway compared to other chILDs. However NEH was also seen in many other chILDs and appears to be most prominent in disorders associated with lung immaturity such as histological patterns associated with surfactant protein-related disorders and pulmonary interstitial glycogenosis. NEH may, to a degree, be a marker of airway immaturity rather than the direct cause of NEHI. This possibility is supported by the fact that the number of bombesin-positive NECs decreased with age in this cohort, independent of disease type. The average percentage of bombesin-positive NECs per airway appears to be the best histological criterion for assessing the extent of NECs in the context of NEHI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Histopathology 02/2015; DOI:10.1111/his.12672 · 3.30 Impact Factor
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    Lung Cancer 01/2015; 87:S10-S11. DOI:10.1016/S0169-5002(15)50027-5 · 3.74 Impact Factor
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    Erik Thunnissen, Birgit I Witte, Andrew G Nicholson
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2015; 10(1):e4. DOI:10.1097/JTO.0000000000000425 · 5.80 Impact Factor
  • Lung Cancer; 01/2015
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    ABSTRACT: Idiopathic, nonspecific interstitial pneumonia (NSIP) is most often associated with various clinical disorders, including connective tissue diseases (CTDs) and chronic hypersensitivity pneumonitis (cHP). Emerging evidence also suggests that "idiopathic" NSIP may be the lung manifestation of undifferentiated CTD (UCTD). However, whether or not NSIP outcome is influenced by the underlying cause remains uncertain. This retrospective study included 127 biopsy-proven NSIP patients (65 women, mean±sd age 55±12 years). Survivals were estimated using a Kaplan-Meier curve and compared using the log-rank test. Multivariate analyses were based on a Cox model. 15 (11.8%) patients had cHP, 29 (22.8%) had CTD, 32 (25.2%) satisfied the Kinder criteria for UCTD and 51 (40.1%) had idiopathic NSIP. At the end of follow-up (mean±sd 64±54 months), a difference in survival was observed between aetiological groups (p=0.002). Survival was better for UCTD than for idiopathic NSIP (p=0.020) and similar to that observed for CTD. cHP survival tended to be poorer than that of idiopathic NSIP (p=0.087) and was an independent predictor of mortality (hazard ratio 2.17, 95% CI 1.05-4.47; p=0.035). NSIP outcome is influenced by its cause. cHP exhibits the highest mortality. UCTD does not differ from CTD supporting the concept of autoimmune NSIP, with a prognosis that is better than that of idiopathic NSIP. Copyright ©ERS 2014.
    European Respiratory Journal 12/2014; 45(3). DOI:10.1183/09031936.00148613 · 7.13 Impact Factor
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    ABSTRACT: Lung cancer classification during the last four decades has undergone major changes and evolution, mostly lead by pathologists who were actively involved in the International Association for the Study of Lung Cancer (IASLC) Pathology Committee. The Committee members have led the development and writing of the second (1981), third (1999 and 2004), and fourth (2015) editions of the World Health Organization classifications on lung tumors. Committee members were responsible for defining and refining the classifications of small-cell carcinoma and adenocarcinoma subtypes that are relevant to their clinical behavior. Particularly notable was development of the 2011 IASLC/American Thoracic Society/European Respiratory Society international, multidisciplinary lung adenocarcinoma classification. The multidisciplinary approach that represents the IASLC culture in research, education, and practice in clinical management of lung cancer patients have paved the way for integrating pathology practice into the new era of personalized cancer care.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2014; 9(12):1740-9. DOI:10.1097/JTO.0000000000000356 · 5.80 Impact Factor
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    ABSTRACT: AimsTailored therapy of lung cancer requires high quality pathology. Tumours must be subtyped accurately and material preserved for genetic analysis upon which treatment is increasingly based. There is a presumption that pathologists have risen to this challenge, but the nature and degree of variation in practice and quality are unknown.Methods and ResultsWe collected detailed information on 1507 consecutive, newly-diagnosed patients referred to 19 UK lung cancer units, ranging from district general hospitals to specialist cardiothoracic units. In only four centres were pathologists handling thoracic biopsies enrolled in the thoracic EQA scheme. Achievement of a positive diagnosis of malignancy ranged from 53 to 88%. Variation in tumour subtypes was wide and the proportion of biopsies classified as merely ‘non-small cell lung cancer, not otherwise specified’ varied from 3 to 20%, despite almost universal use of immunochemistry. The proportion of tumours tested for EGFR gene mutation ranged from 12 to 92%.Conclusions There is considerable variation in practice amongst UK pathologists and arguably in the quality of pathology, raising questions about expertise, adherence to guidelines, rigour of external quality assessment and, ultimately, the reliability of the pathology that underpins the management of lung cancer.This article is protected by copyright. All rights reserved.
    Histopathology 12/2014; DOI:10.1111/his.12638 · 3.30 Impact Factor
  • Andrew G Nicholson
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    ABSTRACT: This presentation reviews the histopathology of the IIPs since the 2002 ATS/ERS classification of IIPs in the light of the 2013 update. The seven histological patterns proposed in 2002 remain, with diagnostic criteria refined but overall unchanged. A multidisciplinary approach is now established as best practice. NSIP is now recognised as a distinct clinicopathological entity. Respiratory bronchiolitis-interstitial lung disease (RB-ILD) is now commonly diagnosed without the need for surgical biopsy. A diagnostic algorithm has been proposed for the correlation of surgical biopsies with imaging in relation to patients with suspected idiopathic pulmonary fibrosis (IPF). Acute exacerbation of IIPs is now well-defined. Some IIP patients remain hard to classify, often due to overlap of patterns, and a classification based on observed disease behaviour is proposed for such patients. Pleuroparenchymal fibroelastosis is included as a rare but distincty clinincopathological entity. Acute fibrinous organising pneumonia and bronchiolocentric interstitial pneumonia are proposed as histologic patterns that may be of benefit in biopsy classification prior to multidisciplinary review, but are not sufficiently characterized to be recognised as distinct clinical entities.
    Pathology 10/2014; 46 Suppl 2:S37. DOI:10.1097/01.PAT.0000454212.97350.f8 · 2.62 Impact Factor

Publication Stats

22k Citations
2,407.87 Total Impact Points

Institutions

  • 2015
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1997–2015
    • Imperial College London
      Londinium, England, United Kingdom
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
  • 1995–2015
    • Royal Brompton and Harefield NHS Foundation Trust
      • • Respiratory Medicine
      • • Department of Paediatrics
      Harefield, England, United Kingdom
  • 2011
    • University College London
      Londinium, England, United Kingdom
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2010
    • University Hospital of Parma
      Parma, Emilia-Romagna, Italy
  • 2009
    • Hampshire County Council
      Winchester, England, United Kingdom
  • 2008–2009
    • The Heart Lung Center
      Londinium, England, United Kingdom
    • Vancouver General Hospital
      • Department of Radiology
      Vancouver, British Columbia, Canada
  • 2007
    • University of Essex
      Colchester, England, United Kingdom
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States
    • Bristol Hospital
      Bristol, Connecticut, United States
  • 2003–2007
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom
    • University of Auckland
      Окленд, Auckland, New Zealand
  • 2000–2007
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2005–2006
    • Memorial Sloan-Kettering Cancer Center
      • Department of Pathology
      New York City, NY, United States
    • London School of Hygiene and Tropical Medicine
      • Department of Medical Statistics
      Londinium, England, United Kingdom
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 2004
    • King's College London
      Londinium, England, United Kingdom
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
  • 2002–2004
    • Royal Berkshire NHS Foundation Trust
      Reading, England, United Kingdom
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2001
    • Hirosaki University
      Khirosaki, Aomori, Japan
  • 1999
    • IEO - Istituto Europeo di Oncologia
      • Division of Thoracic Surgery
      Milano, Lombardy, Italy