Confocal laser endomicroscopy and immunoendoscopy for real-time assessment of vascularization in gastrointestinal malignancies

Abstract

Gastrointestinal cancers represent a major cause of morbidity and mortality, with incomplete response to chemotherapy in the advanced stages and poor prognosis. Angiogenesis plays a crucial part in tumor growth and metastasis, with most gastrointestinal cancers depending strictly on the development of a new and devoted capillary network. Confocal laser endomicroscopy is a new technology which allows in vivo microscopic analysis of the gastrointestinal mucosa and its microvascularization during ongoing endoscopy by using topically or systemically administered contrast agents. Targeting markers of angiogenesis in association with confocal laser endomicroscopic examination (immunoendoscopy), as a future challenge, will add functional analysis to the morphological aspect of the neoplastic process. This review describes previous experience in endomicroscopic examination of the upper and lower digestive tract with emphasis on vascularization, resulting in a broad spectrum of potential clinical applications, and also preclinical research that could be translated to human studies.

Keywords: Acriflavine; Cancer; Confocal laser endomicroscopy; Fluoresceine; Immunoendoscopy.

Figures

Figure 1

Esophageal surface epithelium visualized using intravenous fluorescein. A: Capillary loops (arrows) of the esophageal papillae; B: Dilatation of intercellular spaces and increased vasculature off the papillae in reflux esophagitis; C: Presence of cylindrical epithelial cell and goblet cells (arrows) in the distal esophagus suggesting Barrett’s epithelium.

Figure 2

Confocal laser endomicroscopy of the stomach using intravenous fluorescein. A: Columnar epithelium of the antral gastric mucosa and regulated microvascular matrix; B: Atrophic gastritis with intestinal metaplasia and presence of goblet cells (arrows); C: Early gastric cancer with disorganized tissue architecture, few regular crypts (arrowhead) and very tortuous, dilated, irregular vessels (arrows).

Figure 3

Confocal laser endomicroscopy of the normal colon using intravenous fluorescein. A: Normal aspect of colonic mucosa showing regular architecture of crypts and capillaries of lamina propria (arrows); B: Dark shadows in the lumen of the vessels representing the red blood cells (arrows).

Figure 4

Confocal laser endomicroscopy of the colon using intravenous fluorescein. A: Colon carcinoma with total disorganization of cell architecture, invasion and destruction of the vessels with leakage of fluorescein (arrows); B: Severe inflammatory changes in ulcerative colitis with cellular infiltrate causing an increase in the distance between crypts and excessive vascularity (arrows).

Figure 5

Confocal laser microscopy of the chick embryo chorioallantoic membrane. A: Chick normal chorioallantoic membrane with visualization of large vessels (arrowheads), medium vessels (arrows) and circulating nucleated erythrocytes; B: Fragment of viable human colon cancer tissue (arrows) implanted on chick embryo chorioallantoic membrane.