Epithelial-mesenchymal transition (EMT) is a highly conserved process that has been well characterised in embryogenesis.Studies have shown that the aberrant activation of EMT in adult epithelia can promote tumour metastasis by repressing cell adhesion molecules, including epithelial (E)-cadherin.Reduced intracellular adhesion may allow tumour cells to disseminate and spread throughout the body.A number of transcription proteins of the Snail superfamily have been implicated in EMT.These proteins have been shown to be overexpressed in advanced gastrointestinal (GI) tumours including oesophageal adenocarcinomas, colorectal carcinomas, gastric and pancreatic cancers, with a concomitant reduction in the expression of E-cadherin.Regulators of EMT may provide novel clinical targets to detect GI cancers early, so that cancers previously associated with a poor prognosis such as pancreatic c a n c e r c a n b e d i a g n o s e d b e fo re t h e y b e c o m e inoperable.Furthermore, pharmacological therapies designed to inhibit these proteins will aim to prevent local and distant tumour invasion.
Background: Oesophageal carcinoma accounts for approximately 7000 deaths p.a. in the UK.The majority of cases present with advanced disease with overall 5 year survival less than 12%; in those receiving palliative treatment the median survival is 3-6 months.Aims: To establish the immediate complication rate associated with all methods of palliation used in the management of malignant dysphagia.Whilst these techniques do not affect survival, avoidance of iatrogenic morbidity and mortality is highly desirable.Methods: Data were retrospectively gathered from the West Midlands oesophageal database (1992)(1993)(1994)(1995)(1996).All cases that received palliative therapy were included.
Aims: To inform the debate about upper gastrointestinal cancer care in the UK, the incidence of cancer of the oesophagus and cardia (OGJ) was determined in the West Midlands, a region covering 10 per cent of England and Wales, with particular reference to the methods of treatment. METHODS: The case-notes of 2776 patients diagnosed with oesophageal and OGJ cancer in the 5 years from 1 January 1992 to 31 December 1996 were scrutinized by one experienced surgeon. Tumour types were classified by histology and site, and treatment modalities assessed for 30-day mortality rate together with life-table analyses. RESULTS: Oesophageal cancer was identified in 2188 patients (61 per cent lower, 34 per cent middle, 4 per cent upper), including 999 squamous carcinomas (27 per cent lower, 64 per cent middle, 9 per cent upper) and 995 adenocarcinomas (97 per cent lower, 3 per cent middle), while there were 588 cases of OGJ cancer (94 per cent adenocarcinomas). Resection was the commonest treatment (865 cases; 31 per cent), with a mortality rate of 10 per cent for oesophageal and 4 per cent for OGJ cancer. Palliative resection had a higher mortality rate than radiotherapy (9 versus 3 per cent), compared with 22 per cent for endoscopic palliation, while the 30-day mortality rate was 30 per cent for the 308 patients given no treatment. CONCLUSIONS: Squamous carcinomas and adenocarcinomas of the oesophageal body are now equally common; lower-third and OGJ tumours are predominantly adenocarcinomas. This study provides baseline data for critical appraisal of potential changes in the delivery of upper gastrointestinal cancer in the UK.
There is growing evidence that iron is important in esophageal adenocarcinoma, a cancer whose incidence is rising faster than any other in the Western world. However, how iron mediates carcinogenesis at the molecular level remains unclear. In this study, we investigated the expression of iron transport proteins involved in cellular iron import, export, and storage in the premalignant lesion Barrett's metaplasia and esophageal adenocarcinoma.Perls' staining was used to examine iron deposition in tissue. mRNA expression in samples of Barrett's metaplasia matched with esophageal adenocarcinoma and samples of Barrett's metaplasia without evidence of adenocarcinoma were examined by real-time PCR. Semiquantitative immunohistochemistry was used to examine cellular localization and protein levels. The effect of iron loading on cellular proliferation and iron transporter expression was determined in esophageal cell lines OE33 and SEG-1 using a bromodeoxyuridine assay and real-time PCR, respectively.In the progression of Barrett's metaplasia to adenocarcinoma, there was overexpression of divalent metal transporter 1 (DMT1), transferrin receptor 1, duodenal cytochrome b, ferroportin, and H-ferritin, and these changes were associated with increased iron deposition. Overexpression of DMT1 was further associated with metastatic adenocarcinoma. Iron loading OE33 and SEG-1 cells caused increased cellular proliferation, which was associated with increased H-ferritin and decreased transferrin receptor 1 and DMT1 expression.Progression to adenocarcinoma is associated with increased expression of iron import proteins. These events culminate in increased intracellular iron and cellular proliferation. This may represent a novel mechanism of esophageal carcinogenesis.
To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anaemia and whether it might have a role in colorectal carcinogenesis.Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer. Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localisation was determined using immunohistochemistry.We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was positively associated with increasing T-stage of colorectal cancer (P<0.05). Furthermore, we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repression. This was supported by hepcidin immunoreactivity in colorectal cancer tissue.We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer. However, we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism.
Background: A significant proportion of patients with gastroesophageal reflux disease (GERD) present with atypical symptoms (extraesophageal reflux; EER). The effectiveness of surgical fundoplication in treating classical reflux symptoms is well documented, but the role of surgery in alleviating EER symptoms is less clear. The aim of this study was to review the published literature to determine whether surgical fundoplication is effective in controlling EER. Materials and Methods: A Medline, PubMed, and Cochrane database search was done to find articles on surgery for extraesophageal reflux (1991–2006). Articles on pediatric patients were excluded. The parameters looked at were patient selection, resolution of symptoms, change in the quality of life, and any adverse outcomes. Results: In 25 studies, a variable proportion (15–95%) of patients with various symptoms of EOR improved after surgical fundoplication. The percentage of patients with EER responding to surgery was less than that reported for classical GERD. Conclusions: The majority of patients in most studies seem to improve symptomatically after surgery. However, a small percentage remains unchanged or worsens. The reported studies are so disparate in their methodology that firm conclusions on the role of surgery are difficult. Further studies are needed. These should be large, multicenter, prospective trials comparing medical and surgical treatment with standardized diagnostic criteria for EER. Pre- and post-treatment assessment, the type of surgery performed, and follow-up should be standardized.
Departments of Surgery and Nuclear Medicine, City Hospital, Birmingham, UK Abstracts of the 34th Annual Meeting of the British Nuclear Medicine Society Manchester International Conference Centre, UK, 27–29 March 2006
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