Jasmin A. Holz

Effects of Autofluorescence Imaging on Detection and Treatment of Early Neoplasia in Patients With Barrett's Esophagus

BACKGROUND & AIMS Studies have reported that autofluorescence imaging (AFI) increases targeted detection of high-grade intraepithelial neoplasia (HGIN) and intramucosal cancer (IMC) in patients with Barretts esophagus (BE). We analyzed data from trials to assess the clinical relevance of AFI-detected lesions. METHODS We collected information on 371 patients with BE, along with endoscopy and histology findings, from databases of 5 prospective studies of AFI (mean age, 65 years; 305 male). We compared these data with outcomes of treatment and follow-up. Study end points included the diagnostic value of AFI (proportion of surveillance patients with HGIN or IMC detected only by AFI-targeted biopsies) and value of AFI in selection of therapy (the proportion of patients for which detection of an HGIN or IMC lesion by AFI changed the treatment strategy based on white-light endoscopy or random biopsy analysis). RESULTS Of study participants, 211 were referred for surveillance and 160 were referred for early stage neoplasia; HGIN or IMC were diagnosed in 147 patients. In 211 patients undergoing surveillance, 39 had HGIN or IMC (23 detected by white-light endoscopy, 11 detected by random biopsies, 5 detected by AFI). So, the diagnostic value of AFI was 5 (2%) of 211. In 24 patients, HGIN or IMC was diagnosed using only AFI. In 33 patients, AFI detected additional HGINs or IMCs next to lesions detected by primary white-light endoscopy. Lesions detected by AFI were treated in 57 patients: 26 patients underwent radiofrequency ablation and showed full remission of neoplasia, whereas 31 underwent endoscopic resection and 6 were found to have IMC. The value of AFI in selection of therapy was 6 (2%) of 371. CONCLUSIONS Based on an analysis of data from clinical trials of patients with BE, detection of lesions by AFI has little effect on the diagnosis of early stage neoplasia or therapeutic decision making. AFI therefore has a limited role in routine surveillance or management of patients with BE.

Optimized endoscopic autofluorescence spectroscopy for the identification of premalignant lesions in Barrett's oesophagus.

Objective Fluorescence spectroscopy has the potential to detect early cellular changes in Barrett’s oesophagus before these become visible. As the technique is based on varying concentrations of intrinsic fluorophores, each with its own optimal excitation wavelength, it is important to assess the optimal excitation wavelength(s) for identification of premalignant lesions in patients with Barrett’s oesophagus. Methods The endoscopic spectroscopy system used contained five (ultra)violet light sources (&lgr;exc=369–416 nm) to generate autofluorescence during routine endoscopic surveillance. Autofluorescence spectroscopy was followed by a biopsy for histological assessment and spectra correlation. Three intensity ratios (r1, r2, r3) were calculated by dividing the area, A, under the spectral curve of selected emission wavelength ranges for each spectrum generated by each excitation wavelength &lgr;exc as follows . Double intensity ratios were calculated using two excitation wavelengths. Results Fifty-eight tissue areas from 22 patients were used for autofluorescence spectra analysis. Excitation with 395, 405 or 410 nm showed a significant (P⩽0.0006) differentiation between intestinal metaplasia and grouped high-grade dysplasia/early carcinoma for intensity ratios r2 and r3. A sensitivity of 80.0% and specificity of 89.5% with an area under the ROC curve of 0.85 was achieved using 395 nm excitation and intensity ratio r3. Conclusion Double excitation showed no additional value over single excitation. The combination of 395 nm excitation and intensity ratio r3 showed optimal conditions to discriminate nondysplastic from early neoplasia in Barrett’s oesophagus.

Fluorescence spectroscopy incorporated in an Optical Biopsy System for the detection of early neoplasia in Barrett's esophagus

Endoscopic surveillance is recommended for patients with Barretts esophagus (BE) to detect high-grade intraepithelial neoplasia (HGIN) or early cancer (EC). Early neoplasia is difficult to detect with white light endoscopy and random biopsies are associated with sampling error. Fluorescence spectroscopy has been studied to distinguish non-dysplastic Barretts epithelium (NDBE) from early neoplasia. The Optical Biopsy System (OBS) uses an optical fiber integrated in a regular biopsy forceps. This allows real-time spectroscopy and ensures spot-on correlation between the spectral signature and corresponding physical biopsy. The OBS may provide an easy-to-use endoscopic tool during BE surveillance. We aimed to develop a tissue-differentiating algorithm and correlate the discriminating properties of the OBS with the constructed algorithm to the endoscopists assessment of the Barretts esophagus. In BE patients undergoing endoscopy, areas suspicious for neoplasia and endoscopically non-suspicious areas were investigated with the OBS, followed by a correlating physical biopsy with the optical biopsy forceps. Spectra were correlated to histology and an algorithm was constructed to discriminate between HGIN/EC and NDBE using smoothed linear dicriminant analysis. The constructed classifier was internally cross-validated and correlated to the endoscopists assessment of the BE segment. A total of 47 patients were included (39 males, age 66 years): 35 BE patients were referred with early neoplasia and 12 patients with NDBE. A total of 245 areas were investigated with following histology: 43 HGIN/EC, 66 low-grade intraepithelial neoplasia, 108 NDBE, 28 gastric or squamous mucosa. Areas with low-grade intraepithelial neoplasia and gastric/squamous mucosa were excluded. The area under the receiver operating characteristic curve of the constructed classifier was 0.78. Sensitivity and specificity for the discrimination between NDBE and HGIN/EC of OBS alone were 81% and 58% respectively. When OBS was combined with the endoscopists assesssment, sensitivity was 91% and specificity 50%. If this protocol would have guided the decision to obtain biopsies, half of the biopsies would have been avoided, yet 4/43 areas containing HGIN/EC (9%) would have been inadvertently classified as unsuspicious. In this study, the OBS was used to construct an algorithm to discriminate neoplastic from non-neoplastic BE. Moreover, the feasibility of OBS with the constructed algorithm as an adjunctive tool to the endoscopists assessment during endoscopic BE surveillance was demonstrated. These results should be validated in future studies. In addition, other probe-based spectroscopy techniques may be integrated in this optical biopsy forceps system.

Fluorescence imaging for the detection of early neoplasia in Barrett's esophagus: old looks or new vision?

Early neoplasia arising from Barrett’s esophagus is often small, focally distributed and endoscopically poorly visible, and random four-quandrant biopsies may easily miss early lesions. Advanced imaging techniques, such as (auto)fluorescence-based modalities, aim to increase the detection rate of early lesions or the yield of random biopsies. Fluorescence-based light–tissue interaction has been designed successfully in point-probe differentiating spectroscopy systems or integrated into wide-field endoscopic systems such as autofluorescence imaging (AFI). In this review, we discuss the most recent advances in fluorescence spectroscopy and imaging for detecting early Barrett’s neoplasia. A spectroscopy probe, integrated into regular biopsy forceps, was shown to offer decent discriminatory capabilities, while ensuring spot-on correlation between the measured area and the corresponding histology. With this tool, surveillance endoscopy with random biopsies may become more efficient and sensitive. AFI was shown to increase the targeted detection of early neoplasia. However, random biopsies could compensate for this effect. The clinical impact of AFI on the diagnosis and the treatment of early neoplasia is limited, and yet AFI may offer a novel approach in biomarker-based risk-stratification models. Moreover, in combination with new, readily available contrast agents such as fluorescent lectins, fluorescence imaging may receive renewed interest.

Targeted labeling of an early-stage tumor spheroid in a chorioallantoic membrane model with upconversion nanoparticles

In vivo detection of cancer at an early-stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of an early-stage tumor spheroid (∼500 μm) is realized for the first time in a chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconversion nanoparticles (UCNPs-mAb).