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Summary Oesophageal exposure to duodenogastro-oesophageal refluxate leads to reflux oesophagitis and is implicated in the development of Barrett's metaplasia (BM). NF-κB signalling in epithelial cells is associated with the activation of transcription factors believed to be central to BM development, whilst NF-κB activation in fibroblasts plays a critical role in matrix remodelling. Our aim was to study the effects of acid exposure on NF-κB activation in primary human oesophageal fibroblasts (HOFs) and primary and immortalized oesophageal squames and to investigate any epithelial/stromal interactions in the response of these cells to acid. Primary HOFs and primary and immortalized oesophageal epithelial cells were exposed to acid (pH 7 - pH 4 ≤ 120 min) in single or pulsed treatments. Conditioned medium from epithelial cells following acid exposure was also applied to fibroblasts. Cell viability was determined by MTT-ESTA. NF-κB activation was determined by cellular localization of NF-κB/p65 visualized by immunofluorescence. Conditioned medium from oesophageal epithelial cells, subjected to pH 5 pulsatile exposure, activated NF-κB in fibroblasts, with some inter-patient variability, but these conditions did not directly activate NF-κB in the epithelial cells themselves. Significant NF-κB activation was seen in the epithelial cells but only with greater acidity and exposure times (pH 4, 60-120 min). Our findings show that acid exposure can cause indirect activation of stromal cells by epithelial-stromal interactions. This may contribute to the pathogenesis of oesophageal diseases, and the inter-patient variability may go some way to explain why some patients with reflux oesophagitis develop BM and others do not. [ABSTRACT FROM AUTHOR]

Parberry-Clark C, Bury J P, Cross S S & Winder S J (2011) Histopathology 59, 180-187 Loss of dystroglycan function in oesophageal cancer Aims: Oesophageal cancer is an increasingly common human malignancy, with its incidence in the West rapidly rising. It is associated with a very poor prognosis, and its exact pathogenesis is uncertain. Dystroglycan and E-cadherin are cell adhesion molecules, the loss of which is often related to tumour differentiation, aggressiveness and invasiveness. The aim was therefore to evaluate their roles in oesophageal carcinogenesis. Methods and results: mRNA and protein levels of dystroglycan and E-cadherin were examined in oesophageal normal and tumour tissue samples, and in FLO-1 oesophageal adenocarcinoma cells, using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction. E-cadherin,α-dystroglycan and β-dystroglycan levels were decreased in the oesophageal primary tumour samples, despite the presence of normal levels of dystroglycan mRNA. In FLO-1 cells, increasing cell density caused a decrease in protein levels of β-dystroglycan over time, despite the persistent presence of dystroglycan mRNA. Re-expression of dystroglycan in FLO-1 cells reduced the numbers and size of colonies formed in soft agar, indicative of a role for dystroglycan in suppressing the tumour phenotype. Conclusions: The adenocarcinoma cells mirrored the in vivo situation with respect to dystroglycan function, making this a useful model of oesophageal carcinogenesis; moreover, loss of dystroglycan protein, despite the presence of dystroglycan mRNA, points to a post-translational mechanism of dystroglycan loss. [ABSTRACT FROM AUTHOR]

Background: Adenocarcinomas can arise in a variety of circumstances in which intestinal segments have been used for urinary diversions. Whereas ureterosigmoidostomy is the oldest and simplest form of continent urinary diversion it also seems to be the most dangerous in this regard. Herein we present a case of colonic neoplasia complicating a non-functioning ureterosigmoidostomy after 55 years; the longest latent period documented to date.Case Presentation: A 56-year-old lady born with congenital bladder exystrophy and who had a functional ileal conduit presented to us with a 6 month history of change in bowel habit and rectal bleeding. Prior to this she had had multiple abdominal surgeries as a child and had suffered from lifelong recurrent urinary tract infections. Colonoscopy revealed the presence of two large sessile polyps in close proximity to a diverticulum-like structure that after surgical resection turned out to be a non-functioning ureterosigmoidostomy from when she was an infant.Conclusions: Our case highlights the importance of enrolling patients with ureterosigmoidostomies into long-term colonoscopic surveillance programmes. This is also true for those patients who undergo revisional surgery but have preserved ureteric stumps. Endoscopists should be aware of the varied endoscopic appearances of the anastamosis in order to be able to recognise these structures when present. [ABSTRACT FROM AUTHOR]