In vivo characterization of abnormalities in small-bowel diseases using probe-based confocal laser endomicroscopy^[1]

Abstract

Background and study aims Probe-based confocal laser endomicroscopy (pCLE) enables real-time optical biopsy. Little is known about pCLE imaging deep inside the small bowel, therefore the aim of this study was to determine its usefulness.

Patients and methods Between April 2014 and January 2016, we performed 38 pCLE examinations during double-balloon enteroscopy with intravenous fluorescein in 37 patients with: tumors (n = 10), vascular disorders (n = 6), inflammatory diseases and drug injuries (n = 13), other disorders (n = 4), and normal findings (n = 4). We measured the calibers of capillary and lymphatic vessels at 15 different sites and compared the calibers between pCLE images and histopathology. We also compared pCLE findings with pathologic diagnosis.

Results The inner diameters of capillary vessels beneath the epithelium and in the middle of villi were 16.2 ± 3.0 µm and 14.5 ± 3.1 µm, respectively, in the pCLE images, but these were not consistent with formalin-fixed paraffin-embedded histology. In tumors, larger capillary vessels were observed in aggressive malignant lymphoma and metastasis, and a “soccer ball-like pattern” constituting homogenous dark cells packed with polygonal, narrower capillary vessels was characteristic in pCLE images of a malignant lymphoma follicle. Hereditary hemorrhagic telangiectasia and angiodysplasia contained anastomosis of capillary vessels of different calibers. In IgA vasculitis, segmental capillary strictures were observed. Intestinal lymphangiectasia with protein-losing enteropathy contained a reticular network of lymphatic vessels and dilated lymphatic ducts accompanied by numerous cell gaps. pCLE findings corresponded to pathologic diagnosis in 32 examinations (91 %).

Conclusions pCLE is useful for in vivo analysis of abnormalities of the capillary and lymphatic vessels and epithelium, and for diagnosis in various small-bowel diseases.

Study registration: UMIN 000013857

¹ A poster including part of this material was presented at the American Society for Gastrointestinal Endoscopy (DDW 2015 Washington D.C.) on 18 May 2015.

• References

• 1 Wallace MB, Fockens P. Probe-based confocal laser endomicroscopy. Gastroenterology 2009; 136: 1509-1513
• 2 Wang KK, Carr-Locke DL, Singh SK. et al. Use of probe-based confocal laser endomicroscopy (pCLE) in gastrointestinal applications. A consensus report based on clinical evidence. United Eur Gastroenterol J 2015; 3: 230-254
• 3 Miehlke S, Morgner A, Aust D. et al. Probe-based confocal laser endomicroscopy in double balloon enteroscopy. Z Gastroenterol 2011; 49: 1529-1534
• 4 Ohmiya N, Taguchi A, Shirai K. et al. Endoscopic resection of Peutz-Jeghers polyps throughout the small intestine at double-balloon enteroscopy without laparotomy. Gastrointest Endosc 2005; 61: 140-147
• 5 Arakawa D, Ohmiya N, Nakamura M. et al. Outcome after enteroscopy for patients with obscure GI bleeding: diagnostic comparison between double-balloon endoscopy and videocapsule endoscopy. Gastrointest Endosc 2009; 69: 866-874
• 6 Nguyen DL, Lee JG, Parekh NK. et al. The current and future role of endomicroscopy in the management of inflammatory bowel disease. Ann Gastroenterol 2015; 28: 331-336
• 7 Santi EG, Inoue H, Ikeda H. et al. Microvascular caliber changes in intramucosal and submucosally invasive esophageal cancer. Endoscopy 2013; 45: 585-588
• 8 Deb P, Boruah D, Dutta V. Morphometric study of microvessels in primary CNS tumors and its correlation with tumor types and grade. Microvasc Res 2012; 84: 34-43
• 9 Meining A, Bajbouj M, Schmid RM. Confocal fluorescence microscopy for detection of gastric angiodysplasia. Endoscopy 2007; 39 (Suppl. 01) E145
• 10 Choong CK, Beasley SW. Intra-abdominal manifestations of Henoch-Schonlein purpura. J Paediatr Child Health 1998; 34: 405-409
• 11 Geboes K, Dalle I. Vasculitis and the gastrointestinal tract. Acta Gastroenterol Belg 2002; 65: 204-212
• 12 Matsumoto T, Iida M, Matsui T. et al. Non-specific multiple ulcers of the small intestine unrelated to non-steroidal anti-inflammatory drugs. J Clin Pathol 2004; 57: 1145-1150
• 13 Matsumoto T, Nakamura S, Esaki M. et al. Endoscopic features of chronic nonspecific multiple ulcers of the small intestine: comparison with nonsteroidal anti-inflammatory drug-induced enteropathy. Dig Dis Sci 2006; 51: 1357-1363
• 14 Takenaka H, Ohmiya N, Hirooka Y. et al. Endoscopic and imaging findings in protein-losing enteropathy. J Clin Gastroenterol 2012; 46: 575-580
• 15 Umeno J, Hisamatsu T, Esaki M. et al. A hereditary enteropathy caused by mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. PLoS Genet 2015; 11: e1005581
• 16 Vardy PA, Lebenthal E, Shwachman H. Intestinal lymphangiectasia: a reappraisal. Pediatrics 1975; 55: 842-851
• 17 Ohmiya N, Nakamura M, Yamamura T. et al. Classification of intestinal lymphangiectasia with protein-losing enteropathy: white villi type and non-white villi type. Digestion 2014; 90: 155-166
• 18 Kiesslich R, Duckworth CA, Moussata D. et al. Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease. Gut 2012; 61: 1146-1153
• 19 Canto MI, Anandasabapathy S, Brugge W. et al. In vivo endomicroscopy improves detection of Barrett’s esophagus-related neoplasia: a multicenter international randomized controlled trial (with video). Gastrointest Endosc 2014; 79: 211-221
• 20 Atreya R, Neumann H, Neufert C. et al. In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn’s disease. Nat Med 2014; 20: 313-318