Confocal laser endomicroscopy for superficial esophageal squamous cell carcinoma

Background and study aims: Confocal laser endomicroscopy (CLE) allows subsurface imaging of gastrointestinal mucosa in vivo. The goal of the present study was to compare the endomicroscopic characteristics of cells and intrapapillary capillary loops (IPCLs) in normal and superficial esophageal squamous cell carcinoma (SESC).

Patients and methods: We recruited consecutive patients with SESC diagnosed by conventional endoscopy and confirmed by histopathology between July 2006 and May 2008. The confocal endoscopic images of these patients were collected and compared with the corresponding histology. The characteristic patterns of cells and IPCLs was then analyzed from these images of malignant and normal mucosa. The quality of images and interobserver variations of two endoscopists were also evaluated.

Results: Overall, 64 samples from 57 subjects (27 SESCs, 30 controls) were examined by CLE. The confocal images corresponded to the hematoxylin and eosin staining from the same sites. The confocal images showed that there was a significantly higher proportion of squamous epithelial cells with irregular arrangement (79.4 % vs. 10.0 %, P < 0.001), increased diameter of IPCLs (26.0µm vs. 19.2µm, P < 0.001), and irregular shape IPCLs (82.4 % vs. 36.7 %, P = 0.0002) in the SESC group compared with the controls. Massive IPCLs with tortuous vessels (44.1 % vs. 0 %, P < 0.0001), and long branching IPCLs (23.5 % vs. 3.3 %, P = 0.0204) were frequently observed in the SESC group. In this study, about 35.5 % of images were graded as good quality, and the interobserver agreement for the prediction of cancerous mucosa was graded as substantial.

Conclusions: CLE can be used to distinguish cancerous from normal epithelium, which gives it potential value for early detection of esophageal carcinoma. The difficulty in obtaining good images in the esophagus by CLE is a latent problem.

References

• 1 Wang G Q, Abnet C C, Shen Q. et al . Histological precursors of oesophageal squamous cell carcinoma: results from a 13 year prospective follow up study in a high risk population.  Gut. 2005;  54 187-192
• 2 Hayat M J, Howlader N, Reichman M E. et al . Cancer statistics, trends, and multiple primary cancer analyses from the Surveillance, Epidemiology, and End Results (SEER) Program.  Oncologist. 2007;  12 20-37
• 3 Inoue H, Rey J F, Lightdale C. Lugol chromoendoscopy for esophageal squamous cell cancer.  Endoscopy. 2001;  33 75-79
• 4 Dubuc J, Legoux J L, Winnock M. et al . Endoscopic screening for esophageal squamous-cell carcinoma in high-risk patients: a prospective study conducted in 62 French endoscopy centers.  Endoscopy. 2006;  38 690-695
• 5 Freitag C P, Barros S G, Kruel C D. et al . Esophageal dysplasias are detected by endoscopy with Lugol in patients at risk for squamous cell carcinoma in southern Brazil.  Dis Esophagus. 1999;  12 191-195
• 6 Kumagai Y, Inoue H, Nagai K. et al . Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture of superficial esophageal carcinoma.  Endoscopy. 2002;  34 369-375
• 7 Inoue H, Honda T, Takeshita K. et al . Ultrahigh magnification endoscopic observation of carcinoma in situ in the esophagus.  Dig Endosc. 1997;  9 16-18
• 8 Li X D, Boppart S A, Van Dam J. et al . Optical coherence tomography: advanced technology for the endoscopic imaging of Barrett"s esophagus.  Endoscopy. 2000;  32 921-930
• 9 Kara M A, Peters F P, Fockens P. et al . Endoscopic video-autofluorescence imaging followed by narrow band imaging for detecting early neoplasia in Barrett’s esophagus.  Gastrointest Endosc. 2006;  64 176-185
• 10 Sasajima K, Kudo S E, Inoue H. et al . Real-time in vivo virtual histology of colorectal lesions when using the endocytoscopy system.  Gastrointest Endosc. 2006;  63 1010-1017
• 11 Dumonceau J M, Giostra E, Genta R. et al . In vivo microscopic examination of the esophagus for the detection of cancer before liver transplantation in patients with alcoholic cirrhosis.  Endoscopy. 2006;  38 282-284
• 12 Inoue H, Kudo S, Shiokawa A. Technology insight: laser scanning confocal microscopy and endocytoscopy for cellular observation of gastointestinal tract.  Nat Clin Pract Gastroenterol Hepatol. 2005;  2 31-37
• 13 Inoue H, Sasajima K, Kaga M. et al . Endoscopic in vivo evaluation of tissue atypia in the esophagus using a newly designed integrated endocytoscope: a pilot trial.  Endoscopy. 2006;  38 891-895
• 14 Polglase A L, McLaren W J, Skinner S A. et al . A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract.  Gastrointest Endosc. 2005;  62 686-695
• 15 Pech O, Rabenstein T, Manner H. et al . Confocal laser endomicroscopy for in vivo diagnosis of early squamous cell carcinoma in the esophagus.  Clin Gastroenterol Hepatol. 2008;  6 89-94
• 16 Kiesslich R, Burg J, Vieth M. et al . Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo.  Gastroenterology. 2004;  127 706-713
• 17 Kiesslich R, Gossner L, Goetz M. et al . In vivo histology of Barrett’s esophagus and associated neoplasia by confocal laser endomicroscopy.  Clin Gastroenterol Hepatol. 2006;  4 979-987
• 18 Kitabatake S, Niwa Y, Miyahara R. et al . Confocal endomicroscopy for the diagnosis of gastric cancer in vivo.  Endoscopy. 2006;  38 1110-1114
• 19 Kakeji Y, Yamaguchi S, Yoshida D. et al . Development and assessment of morphologic criteria for diagnosing gastric cancer using confocal endomicroscopy: an ex vivo and in vivo study.  Endoscopy. 2006;  38 886-890
• 20 Kundel H L, Polansky M. Measurement of observer agreement.  Radiology. 2003;  228 303-308
• 21 Hashimoto C L, Iriya K, Baba E R. et al . Lugol’s dye spray chromoendoscopy establishes early diagnosis of esophageal cancer in patients with primary head and neck cancer.  Am J Gastroenterol. 2005;  100 275-282
• 22 Monig H, Arendt T, Eggers S. et al . Iodine absorption in patients undergoing ERCP compared with coronary angiography.  Gastrointest Endosc. 1999;  50 79-81
• 23 Ponchon T. Endoscopic diagnosis of superficial neoplastic lesions of the digestive tract.  Gastroenterol Clin Biol. 2000;  24 B109-B122
• 24 Meyer V, Burtin P, Bour B. et al . Endoscopic detection of early esophageal cancer in a high-risk population: does Lugol staining improve videoendoscopy?.  Gastrointest Endosc. 1997;  45 480-484
• 25 Kumagai Y, Monma K, Kawada K. Maginifying chromoendoscopy of the esophagus: in-vivo pathological diagnosis using an endocytoendoscopy system.  Endoscopy. 2004;  36 590-594
• 26 Kumagai Y, Toi M, Inoue H. Dynamism of tumour vasculature in the early phase of cancer progression: outcomes from oesophageal cancer research.  Lancet Oncol. 2002;  3 604-610
• 27 Sharma P, Wani S, Bansal A. et al . A feasibility trial of Narrow Band Imaging endoscopy in patients with gastroesophageal reflux disease.  Gastroenterology. 2007;  133 454-464
• 28 Kumagai Y, Inoue H, Nagai K. et al . Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture of superficial esophageal carcinoma.  Endoscopy. 2002;  34 369-375
• 29 Deinert K, Kiesslich R, Vieth M. et al . In-vivo microvascular imaging of early squamous-cell cancer of the esophagus by confocal laser endomicroscopy.  Endoscopy. 2007;  39 366-368
• 30 Bollschweiler E, Baldus S E, Schröder W. et al . High rate of lymph-node metastasis in submucosal esophageal squamous-cell carcinomas and adenocarcinomas.  Endoscopy. 2006;  38 149-156