Patients with Barrett's esophagus (BE) undergo periodic endoscopic surveillance with random biopsies in an effort to detect dysplastic or early cancerous lesions. Surveillance may be enhanced by near-infrared Raman spectroscopy (NIRS), which has the potential to identify endoscopically-occult dysplastic lesions within the Barrett's segment and allow for targeted biopsies. The aim of this study was to assess the diagnostic performance of NIRS for identifying dysplastic lesions in BE in vivo. Raman spectra (P<sub>exc</sub>=70 mW; t=5 s) were collected from Barrett's mucosa at endoscopy using a custom-built NIRS system (λ<sub>exc</sub>=785 nm) equipped with a filtered fiber-optic probe. Each probed site was biopsied for matching histological diagnosis as assessed by an expert pathologist. Diagnostic algorithms were developed using genetic algorithm-based feature selection and linear discriminant analysis, and classification was performed on all spectra with a bootstrap-based cross-validation scheme. The analysis comprised 192 samples (112 non-dysplastic, 54 low-grade dysplasia and 26 high-grade dysplasia/early adenocarcinoma) from 65 patients. Compared with histology, NIRS differentiated dysplastic from non-dysplastic Barrett's samples with 86% sensitivity, 88% specificity and 87% accuracy. NIRS identified 'high-risk' lesions (high-grade dysplasia/early adenocarcinoma) with 88% sensitivity, 89% specificity and 89% accuracy. In the present study, NIRS classified Barrett's epithelia with high and clinically-useful diagnostic accuracy.
Photodynamic therapy has been applied to Barrett's esophagus and has been shown in prospective randomized studies to eliminate dysplasia as well as decrease the occurrence of cancer. However, the therapy isnot always effective and there are issues with residual areas of Barrett's mucosa despite therapy. There has not been a good explanation for these residual areas and they seem to imply that there may exist a biological mechanisms by which these cells may be resistant to photodynamic therapy. It was our aim to determine if known abnormalities in Barrett's mucosa could be correlated with the lack of response of some of these tissues. We examined the tissue from mulitpel patients who had resonse to therapy as well as those who did not respond. We assessed the tissue for p53 mutations, inactivatino of p16, ploidy status, cell proliferation, telomerase activity, and degree of dysplasia. Interestingly, the only genetic marker than was found to be correlated with lack of reonse was p53 and telomerase activity. This suggests that cells that have lost mechanisms for cell death such as apoptosis or telomere shortengin may be more resistant to photodynamic therapy. In this study, we examined patients before and after PDT for telomerase activity.
The purpose of this study is to assess if Raman spectroscopy can classify dysplastic (DYS) and early neoplastic lesions within Barrett's esophagus (BE). In BE, the normal squamous epithelium (SQ) lining the esophagus is replaced by columnar epithelium. These patients have a 30-125 fold excess risk of developing adenocarcinoma. Raman spectroscopy may provide diagnostic information so that tissue transformation may be detected at an early stage and improve the patient's prognosis. Ex vivo measurements were carried out initially on biopsy samples obtained from BE patients undergoing routine endoscopic and biopsy surveillance. Differences were noted in the spectral regions 1200-1350 cm<SUP>-1</SUP> and 1550-1640 cm<SUP>-1</SUP> when comparing different histopathologic grades. Principal component analysis of the spectra led to good separation between SE and BE but not between BE and DYS. Improved results were obtained using a probabilistic artificial neural network, with a resultant sensitivity and specificity of 77 percent and 93 percent in differentiating SQ/BE from dysplasia, respectively. Recently, in vivo endoscopic measurements have been performed. These preliminary results indicate that RS in combination with endoscopy may be a useful technique to screen BE patients for dysplastic/early neoplastic lesions.