Barrett's Specimens Research Articles

Enhanced nicotinic receptor mediated relaxations in gastroesophageal muscle fibers from Barrett's esophagus patients

Increased nicotinic receptor mediated relaxation in the gastroesophageal antireflux barrier may be involved in the pathophysiology of reflux. This study is designed to determine whether the defects we previously identified in gastroesophageal reflux disease patients in- vivo are due to abnormalities of the gastric sling, gastric clasp, or lower esophageal circular (LEC) muscle fibers. Muscle strips from whole stomachs and esophagi were obtained from 16 normal donors and 15 donors with histologically proven Barrett's esophagus. Contractile and relaxant responses of gastric sling, gastric clasp, or LEC fibers were determined to increasing concentrations of carbachol and to nicotine after inducing maximal contraction to bethanechol. Muscarinic receptor density was measured using subtype selective immunoprecipitation. Barrett's esophagus gastric sling and LEC fibers have decreased carbachol-induced contractions. Barrett's esophagus sling fibers have decreased M2 -muscarinic receptors and LEC fibers have decreased M3 receptors. Relaxations of all three fiber types are greater in Barrett's esophagus specimens to both high carbachol concentrations and to nicotine following bethanechol precontraction. The maximal response to bethanechol is greater in Barrett esophagus sling and LEC fibers. The increased contractile response to bethanechol in Barrett's specimens indicates that the defect is likely not due to the smooth muscle itself. The enhanced nicotinic receptor mediated response may be involved in greater relaxation of the muscles within the high-pressure zone of the gastroesophageal junction during transient lower esophageal sphincter relaxations and during deglutitive inhibition and may be involved in the pathophysiology of gastroesophageal reflux disease.

Inflammatory infiltration of metaplastic epithelium and correlation to previous diagnosis of esophagitis and Barrett's length

Objective. The contact of the gastric refluxate with the lower esophagus results in an inflammatory-mediated tissue damage. The role of inflammation both in the development and in the advance of Barrett's esophagus (BE) has not been elucidated. The aim of this study was to assess the inflammatory infiltration in metaplastic Barrett's epithelium and to explore the association of microscopic inflammation to healed esophagitis and Barrett's length. Material and methods. Inflammatory infiltration was qualitatively evaluated in well-characterized Barrett's specimens. Esophagitis was healed prior to histological sampling. Univariate comparative analysis was performed based on BE length. Results. Ninety-eight patients (78 male, mean age 58.3 ± 13.3 yrs) were retrospectively studied. Thirty-three cases with long segment BE (LSBE) (33.7%) were spotted. Inflammatory infiltration was mild, moderate, and severe in 35 (35.7%), 54 (55.1%), and 9 (9.1%) specimens, respectively. The samples with moderate/severe inflammatory infiltration were obtained from patients who had more frequently been diagnosed with esophagitis (p = 0.025). Hiatal hernia (p = 0.001), esophagitis (p = 0.019), and previous use of anti-secretory drugs (p = 0.005) were more common in LSBE. Conclusions.Inflammatory infiltration of Barrett's epithelium was largely moderate despite preceding healing of erosions with PPIs. Previous diagnosis of esophagitis correlated to the degree of inflammation. No association of inflammation to Barrett's length was established.

Increased Expression of VEGF, COX-2, and Ki-67 in Barrett’s Esophagus: Does the Length Matter?

Barrett's esophagus (BE) is a major complication of gastroesophageal reflux disease due to its neoplastic potential. The length of the metaplastic epithelium has been associated with cancer risk. Angiogenesis, inflammation, and increased cell proliferation are early events in the malignant sequence. Vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and Ki-67 are indirect markers of these complex mechanisms. To examine the expression of VEGF, COX-2 and Ki-67 in BE and investigate whether there is an association to Barrett's length. Immunohistochemistry for VEGF, COX-2, and Ki-67 was performed in well-characterized Barrett's samples, evaluated using a qualitative scale and compared between long (LSBE) and short (SSBE) segments. The study population consisted of 98 patients (78 men). LSBE and SSBE was diagnosed in 33 (33.7%) and 65 (66.3%) cases, respectively. VEGF was expressed in vascular endothelium of all Barrett's specimens. COX-2 and Ki-67 expression in metaplastic epithelia was strong in 81.6 and 61.2% of the samples, respectively. Ki-67 expression was significantly stronger in LSBE (p=0.035), whereas VEGF expression was significantly increased in SSBE (p=0.031). COX-2 expression was not associated with Barrett's length. VEGF, COX-2, and Ki-67 were overexpressed in the majority of Barrett's samples. The length was inversely associated with VEGF expression and directly associated with Ki-67 expression.

Usefulness of Endoscopic Brushing and Magnified Endoscopy With Narrow Band Imaging (ME-NBI) in Columnar-Lined Esophagus

Background Oesophageal adenocarcinoma has an unexplained male predominance. We hypothesise that male and female oesophageal tissues display differential responses to acid reflux and progression of Barrett's metaplasia. Aims To characterise the gene expression in male and female normal oesophagus and Barrett's metaplasia, to detect gender-specific differences. Methods 12 biopsy samples of normal oesophagus and Barrett's with intestinal metaplasia were obtained (6 males, 6 females). Gene expression profiles were assessed by tissue microarray analysis to determine differences in upregulated gene expression. Realtime PCR was performed to assess differences in the upregulation of key genes (cdx-1, cdx2, PCNA). Results Using a Venn diagram filter to detect genes that were dysregulated in all three stratification pools (normal v Barrett's in males, normal in males v females, Barrett's in males v females), 5 genes were identified: DAZ1, DAZ2, CCL4, RPS4Y1, USP9Y. The expression of DAZ1 is threefold higher in male Barrett's and is localised to the Y-chromosome. PCR results suggest the upregulation of cdx-2 and PCNA in Barrett's metaplasia is greater in males. Conclusion We provide evidence of gender-specific differences in the refluxBarrett's pathway. We have identified a novel set of biomarkers in male Barrett's specimens. Further analysis of these genetic markers through immunohistochemistry and rt-PCR is planned.

Expression of p53, PCNA, and C-erbB-2 in Barrett's metaplasia and adenocarcinoma.

We sought to determine if an immunohistochemical panel of p53, PCNA, and c-erbB-2 was a useful biomarker of transformation in Barrett's metaplasia. P53, PCNA, and c-erbB-2 immunohistochemistry was performed on resected Barrett's specimens selected to show discrete grades of dysplasia and then on prospectively obtained biopsies. In resection specimens, p53 was positive in 36% with no dysplasia, in 30% with low-grade dysplasia, in 85% with high-grade dysplasia, and in 90% of adenocarcinomas. While an evaluation of proliferation throughout the specimen did not differ between groups, surface proliferation was significantly higher in high-grade dysplasia than in low-grade or no dysplasia. All high-grade dysplasia specimens were positive for at least one marker, compared to 44% with no or low-grade dysplasia. C-erbB-2 was only seen in 31% with high-grade dysplasia and in 10% of adenocarcinomas. Prospectively, the panel had a sensitivity of 100%, a specificity of 81% and an overall accuracy of 83% in identifying patients who developed high-grade dysplasia or cancer. Thus, overexpression of p53 occurs early in the malignant transformation of Barrett's and increases with histologic progression, and proliferation at the surface of Barrett's epithelium increases with progressive grades of dysplasia. An immunohistochemical panel of p53 and PCNA is a useful biomarker for Barrett's metaplasia.

On the British Fossil Cretaceous Birds

History . T he oldest remains of British fossil birds are recorded by Sir Charles Lyell as having been first found in 1858, in the Cambridge Upper Greensand. This stratum still continues the only member of the British Secondary deposits in which the bones of birds have been identified by morphological characters; for though the Rev. Mr. Dennis had previously asserted the occurrence of birds in the Stonesfield Slate, on the evidence of the microscopic structure of osseous tissue, it is safer, in the absence of recognizable bones, to believe that the ornithic structure he detected was found in an ornithosaurian rather than in a true bird. The discovery of bird-bones in the Cambridge Greensand was made by Mr. Lucas Barrett, F.G.S., then Assistant Naturalist to the late Professor Sedgwick in the Woodwardian Museum of the University of Cambridge; but I am not aware that Mr. Barrett ever published any account of his discovery. The bones are mentioned by Lyell as “the remains of a bird which was rather larger than the common Pigeon, and probably of the order Natatores, and which, like most of the Gull tribe, had well-developed wings. Portions of the metacarpus, metatarsus, tibia, and femur have been detected; and the determinations of Mr. Barrett have been confirmed by Professor Owen.” What became of Mr. Barrett's specimens I was never able to find out. They were not in the Woodwardian Museum when I succeeded to Mr. Barrett's duties in 1859; and the whole of the remains to which I