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Barrett's metaplasia (BM) is an early lesion in the progression from oesophageal inflammation through dysplasia to the development of Barrett's adenocarcinoma (BA). Previous work indicates that BM and BA are associated with reduced E-cadherin expression and increased cytoplasmic/nuclear pools of its associated protein b-catenin. b-catenin participates in Wnt signalling and activates oncogene transcription by complexing with T-cells factors (TCF). One such oncogene is c-myc. We have previously shown that TNF-a can downregulate E-cadherin expression. Here, we assess TNF-a expression in Barrett's metaplasia and examine if TNF-a can promote b-catenin mediated transcription of oncogenes in a gastrointestinal model system. Employing immunohistochemistry and Western blot analysis of oesophageal tissue, epithelial expression of TNF-a increases with progression along the metaplasia -dysplasia -carcinoma sequence (P50.001). b-catenin mediated transcription was then assessed in TNF-a stimulated cell lines using the TOPFLASH reporter system whilst cmyc expression was assessed by real time PCR. In a columnar intestinal cell model, TNF-a induces c-myc expression which is induced via b-catenin mediated transcription (P50.05). This b-catenin mediated transcription is independent of NF-kB activation. Thus, TNF-a is up-regulated in the progression of Barrett's oesophagus and b-catenin mediated transcription of cmyc is a novel pathway whereby elevated levels of TNF-a may lead to oncogene transcription and altered biology in gastrointestinal epithelia and metaplasia.

Our study provides an update of the incidence of oesophageal cancer in the West Midland region of England and Wales from 1992-96. A total of 2,671 cases of oesophageal cancer were identified during the 5-year study period, with an age-standardised annual incidence (ASR) of 5.24 per 100,000 (95% CI: 5.02, 5.45). Similar numbers of adenocarcinoma and squamous cell carcinoma were found. Only 152 (5.6%) had no histology. There was a 5-fold difference in age-standardised annual incidence rates between males and females for adenocarcinoma of oesophagus, but no gender difference for squamous cell carcinoma. The parallel but higher ASR in males compared to females for adenocarcinoma of both oesophagus and cardia merits further investigation. The similarities in the patterns of age-and sex-specific rates and in the socioeconomic profiles could indicate a common aetiology for adenocarcinoma of oesophagus and gastric cardia. Quality control in Cancer Registries needs to focus on the accuracy and consistency of subsite classification to ensure that trends in incidence are identified. In the absence of accurate subsite classification of stomach cancers, the proportions of adenocarcinoma and squamous cell carcinoma of oesophagus (or the absolute rate of adenocarcinoma of oesophagus) may provide a useful tool in indicating whether adenocarcinoma of gastric cardia is likely to be increasing in incidence.Key words: oesophageal cancer; oesophageal squamous cell carcinoma; oesophageal adenocarcinoma; gastric cardia adenocarcinoma; cancer incidenceThe reported incidence of carcinoma of the oesophagus has been rising steeply in the UK since around 1970, particularly in males. [1][2][3] There have also been reports of rises in other parts of Europe including Denmark 4,5 and Norway 6 as well as in the United States 7 and Australia. 8 Our study provides a reliable update of oesophageal cancer incidence in the West Midlands region of England up to 1996. It also compares squamous cell carcinoma of the oesophagus, adenocarcinoma of the oesophagus and gastric cardia with respect to incidence and socioeconomic deprivation. MATERIAL AND METHODSThe West Midlands region of England and Wales is broadly representative of the country as a whole, with a mix of rural communities and urban conurbations. The population has increased from 4.76 million in 1961, 5.11 in 1971 and 1981 to 5.30 million in 1991. The external boundary has remained the same but as a result of immigration, there has been a change in the ethnic make-up of the region. In the 1991 census, which was the first to include a question on ethnic group, the proportion of nonwhite residents was 8%, of these 37% were Indian, 24% were black, 23% were Pakistani and 10% were of other Asian origin. 9 For the 5-year period 1992-96, a retrospective audit was undertaken of all patients with a reported diagnosis of cancer of oesophagus or gastric cardia. 10 Patients with diagnoses ICD-O C15, C16.0, D00.1 and D00.2 were identified from hospital discharge coding or by local Medical Records Departme...

In this unselected population-based series there was little evidence of a trend of improving 30-day mortality rate with increasing workload, or between workload and long-term survival.

From 1957 to 1976 oesophageal resection for carcinoma was performed in 1119 patients reported to the West Midlands Cancer Registry. The operations were performed on 581 patients by 127 surgeons who averaged three or less resections per annum (the 'occasional' group). These were compared with 538 patients (the 'frequent' group) whose resections were performed by four surgeons who averaged six or more resections per annum. Operative mortality was 39.4 per cent in the 'occasional' group and 21.6 per cent in the 'frequent' group (P less than 0.001). The age adjusted 5-year survival was 11.1 and 15.2 per cent respectively (P less than 0.05) but when the operative deaths were excluded there was no significant difference. We suggest that oesophageal resection for carcinoma should be performed only where there is an acceptably low operative mortality rate.

Between 1957 and 1981, 31,716 cases of gastric cancer were registered in the West Midlands, UK. The age-standardized incidence has shown a decrease from 17.42 per 100,000 population during the first quinquennium to 15.30 per 100,000 in the last. There was an apparent increase in the proportion of proximal lesions with a decrease in the proportion of distal, antral cancers. The stage of disease at diagnosis remained constant with 79 per cent of patients having stage IV disease. Less than 1 per cent presented with stage I disease. As a result, the curative resection rate was 21 per cent. The operative mortality rates for curative partial gastrectomy and total gastrectomy were 13 and 29 per cent respectively. Surgeons undertaking more than nine total gastrectomies annually had an overall mean operative mortality rate of 22 per cent. Overall age-adjusted survival at 5 years was 5 per cent. Survival at 5 years for stage I, II and III disease was 72, 32 and 10 per cent respectively. There was a significant increase in survival time for those treated by curative resection between 1972 and 1981 compared with the previous decade. The implications for the management of gastric cancer are discussed.

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a multicentre randomised Phase III non-inferiority trial comparing a positron emission tomographycomputerised tomography-guided watch-and-wait policy with planned neck dissection in the management of locally advanced (N2/N3) nodal metastases in patients with squamous cell head and neck cancer. Health Technol Assess 2017;21(17). This journal is a member of and subscribes to the principles of the Committee on Publication Ethics (COPE) (www.publicationethics.org/). Health Technology Assessment is indexed and abstracted inEditorial contact: journals.library@nihr.ac.ukThe full HTA archive is freely available to view online at www.journalslibrary.nihr.ac.uk/hta. Print-on-demand copies can be purchased from the report pages of the NIHR Journals Library website: www.journalslibrary.nihr.ac.uk Criteria for inclusion in the Health Technology Assessment journalReports are published in Health Technology Assessment (HTA) if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors.Reviews in Health Technology Assessment are termed 'systematic' when the account of the search appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others. HTA programmeThe HTA programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.The journal is indexed in NHS Evidence via its abstracts included in MEDLINE and its Technology Assessment Reports inform National Institute for Health and Care Excellence (NICE) guidance. HTA research is also an important source of evidence for National Screening Committee (NSC) policy decisions.For more information about the HTA programme please visit the website: http://www.nets.nihr.ac.uk/programmes/hta This reportThe research reported in this issue of the journal was funded by the HTA programme as project number 06/302/129. The contractual start date was in April 2007. The draft report began editorial review in July 2015 and was accepted for publication in June 2016. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily ref...