Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo.

BACKGROUND & AIMS A confocal laser endoscopy system has recently been developed that may allow subsurface imaging of living cells in colonic tissue in vivo. The aim of the present study was to assess its potential for prediction of histology during screening colonoscopy for colorectal cancer. METHODS Twenty-seven patients underwent colonoscopy with the confocal endoscope using acriflavine hydrochloride or fluorescein sodium with blue laser illumination. Furthermore, 42 patients underwent colonoscopy with this system using fluorescein sodium. Standardized locations and circumscript lesions were examined by confocal imaging before taking biopsy specimens. Confocal images were graded according to cellular and vascular changes and correlated with conventional histology in a prospective and blinded fashion. RESULTS Acriflavine hydrochloride and fluorescein sodium both yielded high-quality images. Whereas acriflavine hydrochloride strongly labeled the superficial epithelial cells, fluorescein sodium offered deeper imaging into the lamina propria. Fluorescein sodium was thus used for the prospective component of the study in which 13,020 confocal images from 390 different locations were compared with histologic data from 1038 biopsy specimens. Subsurface analysis during confocal laser endoscopy allowed detailed analysis of cellular structures. The presence of neoplastic changes could be predicted with high accuracy (sensitivity, 97.4%; specificity, 99.4%; accuracy, 99.2%). CONCLUSIONS Confocal laser endoscopy is a novel diagnostic tool to analyze living cells during colonoscopy, thereby enabling virtual histology of neoplastic changes with high accuracy. These newly discovered diagnostic possibilities may be of crucial importance in clinical practice and lead to an optimized rapid diagnosis of neoplastic changes during ongoing colonoscopy.

[1]  L. Yannuzzi,et al.  Complications of intravenous fluorescein injections. , 1989, International ophthalmology clinics.

[2]  J. Pawley,et al.  Handbook of Biological Confocal Microscopy , 1990, Springer US.

[3]  G. Friedman,et al.  A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. , 1992, The New England journal of medicine.

[4]  A. Zauber,et al.  Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. , 1993 .

[5]  P. M. Delaney,et al.  Fiberoptics in Confocal Microscopy , 1995 .

[6]  S. Kudo,et al.  Diagnosis of colorectal tumorous lesions by magnifying endoscopy. , 1996, Gastrointestinal endoscopy.

[7]  R. Lotan,et al.  Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid. , 2000, American journal of obstetrics and gynecology.

[8]  R. Burt.  Colon cancer screening. , 2000, Gastroenterology.

[9]  T. Fujii,et al.  Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK , 2000, The Lancet.

[10]  D. Chung,et al.  The genetic basis of colorectal cancer: insights into critical pathways of tumorigenesis. , 2000, Gastroenterology.

[11]  J. Izatt,et al.  High-resolution endoscopic imaging of the GI tract using optical coherence tomography. , 2000, Gastrointestinal endoscopy.

[12]  M F Dixon,et al.  The Vienna classification of gastrointestinal epithelial neoplasia , 2000, Gut.

[13]  R. Kiesslich,et al.  Chromoendoscopy with Indigocarmine Improves the Detection of Adenomatous and Nonadenomatous Lesions in the Colon , 2001, Endoscopy.

[14]  A B West,et al.  Prevalence and distinctive biologic features of flat colorectal adenomas in a North American population. , 2001, Gastroenterology.

[15]  W. McLaren,et al.  In vivo detection of small subsurface melanomas in athymic mice using noninvasive fiber optic confocal imaging. , 2001, The Journal of investigative dermatology.

[16]  H Stepp,et al.  Diagnosing Cancer in Vivo , 2001, Science.

[17]  J. Pawley,et al.  Limitations on optical sectioning in live-cell confocal microscopy. , 2006, Scanning.

[18]  A. Blum,et al.  Endoscopic Interventions for Preneoplastic and Neoplastic Lesions: Mucosectomy, Argon Plasma Coagulation, and Photodynamic Therapy , 2003, Digestive Diseases.

[19]  Bernhard Nafe,et al.  Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. , 2003, Gastroenterology.

[20]  S. Kudo,et al.  Virtual histology of colorectal lesions using laser-scanning confocal microscopy. , 2003, Endoscopy.

[21]  W. Grady.  Genetic testing for high-risk colon cancer patients. , 2003, Gastroenterology.

[22]  M. George,et al.  Cresyl violet as a fluorophore in confocal laser scanning microscopy for future in-vivo histopathology. , 2003, Endoscopy.

[23]  K. Saigenji,et al.  Routine Chromoendoscopy for Gastrointestinal Diseases: Indications Revised , 2003, Endoscopy.

[24]  Joseph A Izatt,et al.  Criteria for the diagnosis of dysplasia by endoscopic optical coherence tomography. , 2003, Gastrointestinal endoscopy.

[25]  C. Bernstein.  The color of dysplasia in ulcerative colitis. , 2003, Gastroenterology.

[26]  M. Coleman,et al.  Differences in colorectal cancer survival between European and US populations: the importance of sub-site and morphology. , 2003, European journal of cancer.

[27]  S. Woolf,et al.  Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. , 2003, Gastroenterology.

[28]  A. Jemal,et al.  Annual report to the nation on the status of cancer, 1975-2000, featuring the uses of surveillance data for cancer prevention and control. , 2003, Journal of the National Cancer Institute.

[29]  R. Kiesslich,et al.  Perspectives of Chromo and Magnifying Endoscopy: How, How Much, When, and Whom Should We Stain? , 2004, Journal of clinical gastroenterology.

[30]  S S Cross,et al.  Efficacy of high magnification chromoscopic colonoscopy for the diagnosis of neoplasia in flat and depressed lesions of the colorectum: a prospective analysis , 2004, Gut.

[31]  Wendy J. McLaren,et al.  In Vivo Detection of Morphological and Microvascular Changes of the Colon in Association with Colitis Using Fiberoptic Confocal Imaging (FOCI) , 2002, Digestive Diseases and Sciences.

[32]  Peter Delaney,et al.  In Vivo Detection of Experimental Ulcerative Colitis in Rats Using Fiberoptic Confocal Imaging (FOCI) , 2001, Digestive Diseases and Sciences.

[33]  M F Neurath,et al.  Surveillance colonoscopy in ulcerative colitis: magnifying chromoendoscopy in the spotlight , 2004, Gut.