Benjamin T. Go

Utility of confocal laser endomicroscopy in identifying high-grade dysplasia and adenocarcinoma in Barrett's esophagus: a systematic review and meta-analysis.

Confocal laser endomicroscopy (CLE) is a novel endoscopic technique that has emerged as an important tool in the in-vivo visualization and detailed assessment of the mucosal layer and subcellular structures in Barrett’s esophagus. Current guidelines recommend four-quadrant random biopsies for identification of high-grade dysplasia (HGD) in Barrett’s esophagus. However, random biopsies are associated with sampling error and inconsistent histopathologic interpretation. CLE, by providing targeted biopsies, could decrease the sampling error and increase the yield of detection of HGD/adenocarcinoma [esophageal adenocarcinoma (EAC)]. We carried out a meta-analysis to evaluate the diagnostic accuracy of the CLE-based targeted biopsies in detecting HGD/adenocarcinoma compared with four-quadrant random biopsies. A search using medical subject headings (MeSH) terms and keywords was performed in the MEDLINE and Cochrane review databases and relevant studies were identified. All the studies that compared the diagnostic yield from CLE-based targeted biopsies to detect HGD/adenocarcinoma with a gold standard of histopathology were included and a meta-analysis was carried out to estimate the pooled sensitivity, specificity, and positive and negative likelihood ratios using Meta-Disc software. There were a total of seven studies with 345 patients and 3080 lesions that were finally included in the meta-analysis. All the studies had reported per-lesion analyses; however, only four of the seven studies had data reported on per-patient analyses. ‘Per-lesion’ analysis for the diagnosis of HGD/adenocarcinoma yielded a pooled sensitivity and specificity of 68% [95% confidence interval (CI) of 64–73%] and 88% (95% CI of 87–89%), respectively. The pooled positive and negative likelihood ratios were 6.56 (95% CI of 3.61–11.90) and 0.24 (95% CI of 0.09–0.63), respectively. Similar numbers were calculated on the basis of ‘per-patient’ basis, which showed a pooled sensitivity and specificity of 86% (95% CI of 74–96%) and 83% (95% CI of 77–88%), respectively. The pooled positive and negative likelihood ratios were 5.61 (95% CI of 2.00–15.69) and 0.21 (95% CI of 0.08–0.59), respectively. CLE, by providing targeted biopsies, has a good diagnostic accuracy in identifying HGD/EAC; however, the overall prevalence of HGD/EAC in the studies included was much higher than what would be seen in clinical practice and these results should be interpreted with caution. Because of its relatively low sensitivity and negative predictive value, CLE may currently not replace standard biopsy techniques for the diagnosis of HGD/EAC in Barrett’s esophagus.

S1939 Prospective Analysis of the Role of CA 19-9 Levels Before and After Endoscopic Decompression of Biliary Obstruction in Differentiating Benign From Malignant Etiologies of Biliary Obstruction

Introduction: The whole genomic microarrays can contribute to high-throughput biomarker screening in colorectal diseases, but the further possible diagnostic utilization of the markers requires testing their classificatory efficacy on an independent sample set. Aims: Our aims were to identify characteristic transcript sets in order to develop diagnostic mRNA expression patterns for objective classification of benign and malignant colorectal diseases and to test their classificatory power on an independent biopsy set. Material and methods: Gene expression profiles were evaluated on HGU133plus2 microarrays from colonic biopsies of 22 patients with colorectal cancer (CRC), 20 with adenoma, 21 with IBD and 11 healthy controls. For classification Prediction Analysis of Microarrays were used. The previously determined classificatory transcript sets were tested on independent samples (27 CRC, 29 adenoma, 28 IBD and 38 normal controls). Array real-time PCR validation was done on 68 independent biopsy specimen (24 CRC, 24 adenoma, 20 normal controls). Receiving operating characteristic (ROC) curve analysis was used to evaluate the discriminatory power of the gene panels. Results: Between normal and CRC samples 38 classifiers were identified by microarray analysis including upregulated CXCL1 and CXCL2 oncogenes, osteopontin and downregulated carbonic anhydrase 7. According to these classifiers, the independent CRC and normal biopsies could be clearly separated by 97.4% specificity and 96.3% sensitivity. Adenoma and normal samples could be classified using 20 discriminatory transcripts such as overexpressed cadherin 3, KIAA1199, forkhead box Q1 and downregulated claudin 8, peptide YY. Using these classifiers, independent adenoma and healthy samples could be distinguished with 94.7% specificity and 100% sensitivity. The microarray results were confirmed on independent biopsies using real-time PCR cards. Discriminatory power of the CRC vs. normal gene panel is proved to be considerably high in array real-time PCR (sensitivity: 91.7 %, specificity: 95.0 %). According to the real-time PCR results, adenoma and healthy samples could be clearly separated, only 2 of the 24 adenoma samples were grouped into the normal cluster. The ROC curve analysis showed 95.8% sensitivity and 100% specificity values. Conclusion: Discriminatory transcripts were identified which could correctly classify CRC and adenoma biopsies also on a large independent sample set. These markers can establish the basis of gene expression based diagnostic classification of benign and malignant colorectal diseases. Diagnostic real-time PCR cards can become part of the automated routine procedure.

New approach in the management of proximally migrated stent with an obstructing anti-reflux valve

New approach in the management of proximally migrated stent with an obstructing anti-reflux valve