Advertisement

The learning curve, interobserver, and intraobserver agreement of endoscopic confocal laser endomicroscopy in the assessment of mucosal barrier defects

  • Jeff Chang
    Affiliations
    Gastroenterology and Liver Services, Bankstown Hospital, Sydney South West Local Health District, Sydney, New South Wales, Australia

    Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
    Search for articles by this author
  • Matthew Ip
    Affiliations
    Gastroenterology and Liver Services, Bankstown Hospital, Sydney South West Local Health District, Sydney, New South Wales, Australia

    Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
    Search for articles by this author
  • Michael Yang
    Affiliations
    Gastroenterology and Liver Services, Bankstown Hospital, Sydney South West Local Health District, Sydney, New South Wales, Australia

    Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
    Search for articles by this author
  • Brendon Wong
    Affiliations
    Gastroenterology and Liver Services, Bankstown Hospital, Sydney South West Local Health District, Sydney, New South Wales, Australia

    Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
    Search for articles by this author
  • Theresa Power
    Affiliations
    Department of Histopathology, Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia

    Faculty of Medicine, The University of Notre Dame, Sydney, New South Wales, Australia
    Search for articles by this author
  • Lisa Lin
    Affiliations
    Department of Histopathology, Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia

    Faculty of Medicine, The University of Notre Dame, Sydney, New South Wales, Australia
    Search for articles by this author
  • Wei Xuan
    Affiliations
    Ingham Institute of Applied Medical Research, Sydney, New South Wales, Australia
    Search for articles by this author
  • Tri Giang Phan
    Affiliations
    Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia

    Immunology Division, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia
    Search for articles by this author
  • Rupert W. Leong
    Correspondence
    Reprint requests: Rupert W. Leong, MBBS, FRACP, MD, AGAF, Gastroenterology and Liver Services, Bankstown-Lidcombe and Concord Hospital, Concord Hospital, Level 1 West, Hospital Rd., Concord, NSW 2137 Australia.
    Affiliations
    Gastroenterology and Liver Services, Bankstown Hospital, Sydney South West Local Health District, Sydney, New South Wales, Australia

    Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia

    Immunology Division, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia

    Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia
    Search for articles by this author
Published:September 03, 2015DOI:https://doi.org/10.1016/j.gie.2015.08.045

      Background and Aims

      Confocal laser endomicroscopy can dynamically assess intestinal mucosal barrier defects and increased intestinal permeability (IP). These are functional features that do not have corresponding appearance on histopathology. As such, previous pathology training may not be beneficial in learning these dynamic features. This study aims to evaluate the diagnostic accuracy, learning curve, inter- and intraobserver agreement for identifying features of increased IP in experienced and inexperienced analysts and pathologists.

      Methods

      A total of 180 endoscopic confocal laser endomicroscopy (Pentax EC-3870FK; Pentax, Tokyo, Japan) images of the terminal ileum, subdivided into 6 sets of 30 were evaluated by 6 experienced analysts, 13 inexperienced analysts, and 2 pathologists, after a 30-minute teaching session. Cell-junction enhancement, fluorescein leak, and cell dropout were used to represent increased IP and were either present or absent in each image. For each image, the diagnostic accuracy, confidence, and quality were assessed.

      Results

      Diagnostic accuracy was significantly higher for experienced analysts compared with inexperienced analysts from the first set (96.7% vs 83.1%, P < .001) to the third set (95% vs 89.7, P = .127). No differences in accuracy were noted between inexperienced analysts and pathologists. Confidence (odds ratio, 8.71; 95% confidence interval, 5.58-13.57) and good image quality (odds ratio, 1.58; 95% confidence interval, 1.22-2.03) were associated with improved interpretation. Interobserver agreement κ values were high and improved with experience (experienced analysts, 0.83; inexperienced analysts, 0.73; and pathologists, 0.62). Intraobserver agreement was >0.86 for experienced observers.

      Conclusion

      Features representative of increased IP can be rapidly learned with high inter- and intraobserver agreement. Confidence and image quality were significant predictors of accurate interpretation. Previous pathology training did not have an effect on learning.

      Abbreviations:

      CDO (cell dropout), CI (confidence interval), CJE (cell-junction enhancement), CLE (confocal laser endomicroscopy), CLS (confocal leak score), eCLE (endoscopic confocal laser endomicroscopy), FL (fluorescein leak), IBD (inflammatory bowel disease), IP (intestinal permeability), OR (odds ratio)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Gastrointestinal Endoscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Salim S.Y.
        • Soderholm J.D.
        Importance of disrupted intestinal barrier in inflammatory bowel diseases.
        Inflamm Bowel Dis. 2011; 17: 362-381
        • Turner J.R.
        Intestinal mucosal barrier function in health and disease.
        Nat Rev Immunol. 2009; 9: 799-809
        • Watson A.J.
        • Duckworth C.A.
        • Guan Y.
        • et al.
        Mechanisms of epithelial cell shedding in the Mammalian intestine and maintenance of barrier function.
        Ann N Y Acad Sci. 2009; 1165: 135-142
        • Watson A.J.
        • Hughes K.R.
        TNF-alpha-induced intestinal epithelial cell shedding: implications for intestinal barrier function.
        Ann N Y Acad Sci. 2012; 1258: 1-8
        • McGuckin M.A.
        • Eri R.
        • Simms L.A.
        • et al.
        Intestinal barrier dysfunction in inflammatory bowel diseases.
        Inflamm Bowel Dis. 2009; 15: 100-113
        • Irvine E.J.
        • Marshall J.K.
        Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk.
        Gastroenterology. 2000; 119: 1740-1744
        • Paramsothy S.
        • Leong R.W.
        Endoscopy: fluorescein contrast in confocal laser endomicroscopy.
        Nat Rev Gastroenterol Hepatol. 2010; 7: 366-368
        • Arslan G.
        • Atasever T.
        • Cindoruk M.
        • et al.
        51CrEDTA colonic permeability and therapy response in patients with ulcerative colitis.
        Nucl Med Commun. 2001; 22: 997-1001
        • Arrieta M.C.
        • Bistritz L.
        • Meddings J.B.
        Alterations in intestinal permeability.
        Gut. 2006; 55: 1512-1520
        • DeMeo M.T.
        • Mutlu E.A.
        • Keshavarzian A.
        • et al.
        Intestinal permeation and gastrointestinal disease.
        J Clin Gastroenterol. 2002; 34: 385-396
        • Neumann H.
        • Kiesslich R.
        • Wallace M.B.
        • et al.
        Confocal laser endomicroscopy: technical advances and clinical applications.
        Gastroenterology. 2010; 139: 388-392
        • De Palma G.D.
        Confocal laser endomicroscopy in the “in vivo” histological diagnosis of the gastrointestinal tract.
        World J Gastroenterol. 2009; 15: 5770-5775
        • Nguyen N.Q.
        • Leong R.W.
        Current application of confocal endomicroscopy in gastrointestinal disorders.
        J Gastroenterol Hepatol. 2008; 23: 1483-1491
        • Othman M.O.
        • Wallace M.B.
        Confocal laser endomicroscopy: is it prime time?.
        J Clin Gastroenterol. 2011; 45: 205-206
        • Leong R.W.
        • Nguyen N.Q.
        • Meredith C.G.
        • et al.
        In vivo confocal endomicroscopy in the diagnosis and evaluation of celiac disease.
        Gastroenterology. 2008; 135: 1870-1876
        • Kiesslich R.
        • Duckworth C.A.
        • Moussata D.
        • et al.
        Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease.
        Gut. 2012; 61: 1146-1153
        • Leong R.
        • Wong B.
        • Chen J.
        • et al.
        Intestinal mucosal leakage is detected using in vivo confocal endomicroscopy in macroscopically-normal Crohn's disease and ulcerative colitis [abstract].
        J Gastroenterol Hepatol. 2012; 27: AB109
        • Leong R.W.
        • Arshi M.
        • Chang J.
        • et al.
        Acute tumour necrosis factor administration induces transient epithelial cell shedding, mucosal leak and neutrophil recruitment to the gut in a mouse model.
        J Gastroenterol Hepatol. 2014; 29: 11
        • Fritscher-Ravens A.
        • Schuppan D.
        • Ellrichmann M.
        • et al.
        Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome.
        Gastroenterology. 2014; 147: 1012-1020
        • Hoffman A.
        • Rey J.W.
        • Mueller L.
        • et al.
        Analysis of interobserver variability for endomicroscopy of the gastrointestinal tract.
        Dig Liver Dis. 2014; 46: 140-145
        • Buchner A.M.
        • Gomez V.
        • Heckman M.G.
        • et al.
        The learning curve of in vivo probe-based confocal laser endomicroscopy for prediction of colorectal neoplasia.
        Gastrointest Endosc. 2011; 73: 556-560
        • Kuiper T.
        • Kiesslich R.
        • Ponsioen C.
        • et al.
        The learning curve, accuracy, and interobserver agreement of endoscope-based confocal laser endomicroscopy for the differentiation of colorectal lesions.
        Gastrointest Endosc. 2012; 75: 1211-1217
        • Wallace M.B.
        • Sharma P.
        • Lightdale C.
        • et al.
        Preliminary accuracy and interobserver agreement for the detection of intraepithelial neoplasia in Barrett's esophagus with probe-based confocal laser endomicroscopy.
        Gastrointest Endosc. 2010; 72: 19-24
        • Liu J.
        • Li M.
        • Li Z.
        • et al.
        Learning curve and interobserver agreement of confocal laser endomicroscopy for detecting precancerous or early-stage esophageal squamous cancer.
        PLoS One. 2014; (4;9:e99089)
        • Kiesslich R.
        • Goetz M.
        • Angus E.M.
        • et al.
        Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy.
        Gastroenterology. 2007; 133: 1769-1778
        • Turcotte J.F.
        • Kao D.
        • Mah S.J.
        • et al.
        Breaks in the wall: increased gaps in the intestinal epithelium of irritable bowel syndrome patients identified by confocal laser endomicroscopy (with videos).
        Gastrointest Endosc. 2013; 77: 624-630