Detection of superficial esophageal squamous cell neoplasia by chromoendoscopy-guided confocal laser endomicroscopy

Abstract

Aim: To evaluate the diagnostic potential of Lugol's chromoendoscopy-guided confocal laser endomicroscopy (CLE) in detecting superficial esophageal squamous cell neoplasia (ESCN).

Methods: Between December 2008 and September 2010, a total of 52 patients were enrolled at the Chinese PLA General Hospital in Beijing, China. First, Lugol's chromoendoscopy-guided CLE was performed in these patients and the CLE in vivo histological diagnosis was recorded. Then, chromoendoscopy-guided biopsy was performed in the same patients by another endoscopist who was blinded to the CLE findings. Based on the biopsy and CLE diagnosis, en bloc endoscopic resection was performed. The CLE in vivo diagnosis and the histological diagnosis of biopsy of ESCN were compared, using a histological examination of the endoscopic resection specimens as the standard reference.

Results: A total of 152 chromoendoscopy-guided biopsies were obtained from 56 lesions. In the 56 lesions of 52 patients, a total of 679 CLE images were obtained vs 152 corresponding biopsies. The sensitivity, specificity, negative predictive value and positive predictive value of chromoendoscopy-guided CLE compared with biopsy were 95.7% vs 82% (P < 0.05), 90% vs 70% (P < 0.05), 81.8% vs 46.7% (P < 0.05), and 97.8% vs 92.7% (P > 0.05), respectively. There was a significant improvement in sensitivity, specificity, negative predictive value, and accuracy when comparing chromoendoscopy-guided CLE with biopsy.

Conclusion: Lugol's chromoendoscopy-guided CLE is a real-time, non-invasive endoscopic diagnostic technology; the accuracy of the detection of superficial ESCN is equivalent to or may be superior to biopsy histology.

Trial registration: ClinicalTrials.gov NCT01156064 NCT01378507.

Keywords: Chromoendoscopy; Confocal endomicroscopy; Endoscopic submucosal dissection; Squamous cell neoplasm; Superficial esophageal neoplasia.

Figures

Figure 1

Flow chart of lesion recruitment. All the endoscopic procedures were performed with the patients under conscious sedation with intravenous midazolam, propofol, fentanyl, or pethidine. Cardiorespiratory function was continually monitored throughout the procedure. CLE: Confocal laser endomicroscopy; ER: Endoscopic resection.

Figure 2

Confocal laser endomicroscopy images of esophageal superficial squamous cell neoplasia. A: Confocal laser endomicroscopy (CLE) scanning; squamous cells (yellow arrow) are homogeneous, while the indicated squamous cells (red arrow) are irregularly arranged with a distinct size and morphology. Capillary leakage of fluorescein sodium is observed; B: Pathological images; the yellow arrow indicates homogeneous cells; the red arrow indicates disordered cell arrangement. The cells have a distinct size and morphology, which is in accordance with CLE.

Figure 3

Confocal laser endomicroscopy images showing different intraepithelial papillary capillary loop changes in the esophageal lesions. A: Regular squamous esophageal epithelium with regular intraepithelial papillary capillary loops (IPCLs) and epithelial cells; B: Some tortuous IPCLs are seen in the non-neoplastic inflammatory lesion; C: Various shapes of twisted IPCLs (red arrow) are seen in the low-grade intraepithelial neoplasia lesion; D: Obvious caliber and shape changes with a larger diameter IPCL (blue arrow) are seen in the high-grade intraepithelial neoplasia lesion; E: Tumor vessels (yellow arrow) are seen in esophageal squamous cell carcinoma.

Figure 4

En bloc endoscopic resection for esophageal lesions. A: Lugol’s iodine chromoendoscopy showed an unstained lesion located in the esophagus; B: The marks surrounding the lesion are at least 5 mm away from the lesion; C: Upper gastrointestinal endoscopy showed an artificial ulceration after ESD; D: En bloc resected specimen. 3.0 cm × 3.0 cm; E: The resected specimen was fixed in 10% formaldehyde solution and continuously sliced into 2 mm sections from the proximal end to the distal end for pathology.