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Barrett's esophagus (BE) goes through a sequence of low grade dysplasia (LGD) and high grade dysplasia (HGD) to esophageal adenocarcinoma (EAC). The current gold standard for BE outcome prediction, histopathological staging, can be unreliable. TP53 abnormalities may serve as prognostic biomarkers. TP53 protein accumulation detected by immunohistochemistry (IHC) indirectly assesses TP53 mutations. DNA fluorescent in situ hybridization (FISH) on brush cytology specimens directly evaluates gene locus loss. We evaluated if IHC and FISH are complementary tools to assess TP53 abnormalities and tested their prognostic value in a long-term prospective follow-up of a BE cohort. TP53 IHC on tissue sections and FISH on brush cytology specimens were evaluated for 116 BE patients with respect to the different histological stages. The TP53 abnormalities were further studied in a panel of cell lines representative of the Barrett's carcinogenic sequence. For 91patients, the predictive value of TP53 abnormalities with respect to progression to HGD/EAC was tested after long term follow-up. The frequency of IHC and FISH TP53 abnormalities increased significantly with increasing histological stage (P 0.001, Chi(2) -test). Combining the techniques detected TP53 abnormalities in 100% of patients with LGD, HGD, and EAC. Multivariate analysis showed that IHC (hazard ratio: 17, 95% CI: 3.2-96, P = 0.001) and FISH (hazard ratio: 7.3, 95% CI: 1.3-41, P = 0.02) were both independent significant predictors of progression. Combining FISH and IHC in assessing TP53 abnormalities leads to an increased detection rate of TP53 aberrations and improved accuracy for predicting BE progression.

Cholangiocarcinomas of different locations differ in growth patterns, symptoms, treatment response, and survival. Still, they are regarded in many studies as a uniform malignancy. Because intra- (iCCA) and extrahepatic (eCCA) cholangiocarcinoma display such differences, we performed a systematic review and meta-analysis to analyze differences in the immunohistochemical profile of these tumors.In February 2014, we searched the two main medical literature databases MEDLINE and EMBASE. We extracted risk ratios and 95% confidence intervals from the identified studies and performed random-effects model meta-analyses in accordance with PRISMA and REMARK guidelines.A total of 54 cohort studies, including 4458 patients and studying 102 individual markers met the inclusion criteria. Of the 57 markers that were evaluated in more than 30 iCCA and eCCA patients, 18 showed a statistically significant difference in expression between iCCA and eCCA. Biomarkers expressed differently between iCCA and eCCA included potential targets of therapy: EGFR, c-erbB-2 and VEGF-A. Several markers showed no statistical difference but large 95% confidence intervals, suggesting insufficient sample size.This systematic review shows differences in marker expression between iCCA and eCCA. Consequently, patients with iCCA and eCCA may benefit from different treatment strategies.

Because formaldehyde is toxic and creates cross-links that may hinder immunohistochemical studies, we tested 3 new cross-linking (F-Solv [Adamas, Rhenen, the Netherlands]) and non-cross-linking (FineFIX [Milestone, Bergamo, Italy] and RCL2 [Alphelys, Plaisir, France]) alcohol-based fixatives for routine staining in comparison with neutral buffered formalin (NBF) as the "gold standard." Fresh tissue samples were divided into 4 equal pieces and fixed in all fixatives for varying times. After paraffin embedding, HE staining, 7 common histochemical stains, and 9 common immunohistochemical stains were performed. RCL2 fixation resulted in soft and slippery tissue, causing sectioning difficulties. F-Solv and FineFIX led to partial tissue disintegration during fixation. F-Solv performed morphologically similar to NBF but needed considerable protocol adjustments before being applicable in daily histologic and immunohistochemical practice. FineFIX did not necessitate major protocol changes but caused shrinkage artifacts, degranulation, and lysis of RBCs. RCL2 generated morphologically overall good results without major protocol changes but caused pigment deposition, degranulation, and RBC lysis. The alcohol-based fixatives had positive and negative attributes and environmental drawbacks, and none was overall comparable to NBF with regard to macroscopy, morphologic evaluation, and immunohistochemical studies.

BACKGROUND: Radiofrequency ablation is safe and effective for complete eradication of nondysplastic Barrett esophagus (BE). The aim was to report the combined results of two published and two ongoing studies on radiofrequency ablation of BE with early neoplasia, as presented at SSAT presidential plenary session DDW 2008. METHODS: Enrolled patients had BE

Background: Autofluorescence imaging is a novel imaging technique that may improve the detection of early, neoplasia in Barrett's esophagus. Autofluorescence imaging is, however, associated with a 40% to 81% false-positive rate. Objective: Our purpose was to identify endoscopic features that may predict the presence of early neoplasia in autofluorescence-positive areas. Design: Descriptive and prospective cohort study. Setting: Tertiary referral centers for the detection and treatment of early Barrett's neoplasia. Patients and Methods: Patients Undergoing autofluorescence endoscopy High-quality images with autofluorescence imaging and white-light endoscopy were obtained with corresponding histologic study A systematic image evaluation process was performed, including an unblinded orientation phase (10 areas), a blinded derivation phase, and a blinded validation phase by 5 international experts in autofluorescence imaging (80 areas). Subsequently the identified features were validated in a prospective pilot study. Main Outcome Measurements: Association between endoscopic features and presence of early neoplasia in autofluorescence-positive areas. Results: Autofluorescence intensity, proximity of gastric folds

Epstein-Barr virus (EBV) has been suggested to play a role in hepatocellular carcinoma (HCC). However, reports on detailed EBV transcript analyses in HCCs are limited. It was shown recently that expression of the transforming BARF1 (BamHI A rightward open reading frame 1) gene of EBV is restricted to latently EBV-infected epithelial malignancies, i.e. nasopharyngeal carcinoma and gastric carcinoma. The aim of this study was to test the presence of EBV in Dutch HCCs. A semiquantitative DNA PCR-enzyme immunoassay (PCR-EIA) for the BamHI W fragment of EBV was used to assess the presence of EBV in frozen and paraffin-embedded tissues of 16 HCCs. In addition, several RNA detection techniques, i.e. nucleic acid sequence-based amplification (NASBA), RT-PCR, RNA in situ hybridization (RISH) and immunohistochemistry (IHC), were applied. Five of 16 HCCs and two of four hepatitis C virus hepatitis samples were weakly positive for EBV DNA by PCR-EIA. Using sensitive RNA transcription techniques, no transcripts were found for BARF1, EBNA-1 and BARTs (BamHI A rightward transcripts) in any of the liver tissues tested. In addition, RISH for EBER1/2 and BARTs and IHC for EBNA-1, LMP-1 and ZEBRA, performed on the paraffin-embedded tissue of the PCR-EIA-positive cases and on adjacent non-neoplastic liver tissues, were negative. The absence of epithelial-specific BARF1 transcripts and other EBV transcripts and proteins in the EBV DNA PCR-positive cases argues strongly against a role for EBV in HCC.