SummaryBackgroundOesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus.MethodsThe Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77.FindingsBetween March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2–9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01–1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98–1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01–1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14–2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events.InterpretationHigh-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus.FundingCancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.
Background and aims-To ascertain the causes of raised aspartate aminotransferase (AST) presumed to be of hepatic origin in two hospitals and the local community served by a centralised biochemistry laboratory. Methods-From June 1996 to February 1997 all patients with AST greater than 400 U/l were identified by the biochemistry laboratory; the patients' clinical records were studied to determine the diagnosis, the clinical outcome, and whether the raised AST and its significance had been noted. Results-A total of 137 patients with a hepatic cause for the raised AST were found. The cause of the raised AST was hepatic ischaemia/hypoxia in 68, pancreatobiliary disease in 33, primary hepatocellular disease in 23, hepatic malignancy in five, and hepatic haematoma in one. In seven patients the diagnosis was unclear. The overall mortality was high (22%) with the highest mortality in the hepatic ischaemia group (37%). The recording and interpretation of the causes of raised AST was poor with only 48% having the correct diagnosis. In 38% the raised AST was apparently not noticed by the attending clinicians. Conclusions-The commonest cause of a hepatitis like biochemical picture was hepatic hypoxia (50%) followed by pancreatobiliary disease (24%). Drug induced hepatic necrosis (8.8%) was uncommon and viral hepatitis was rare (3.6%). AST concentrations returned towards normal most rapidly in patients with hepatic hypoxia and calculous biliary obstruction. Hepatitis, viral or otherwise, is an uncommon cause of a typical hepatitic biochemical result in this community. (Gut 1999;45:129-133)
Aims-(1)A prospective analysis of clinically obvious jaundice (bilirubin >120 µmol/l) in South Wales to determine accuracy of diagnosis, referral pattern, treatment, and outcome. (2) To compare British gastroenterologists' and local general practitioners' perceptions of common causes of jaundice with our study findings. Methods-Over a seven month period all patients with bilirubin >120 µmol/l (excluding neonates with physiological jaundice) were identified by a biochemistry laboratory serving three general hospitals and the community. Clinical data were recorded prospectively. Sixty nine consultant gastroenterologists and 67 local general practitioners (GPs) were asked to cite the commonest causes of bilirubin >120 µmol/l in their experience. Results-A total of 121 patients were identified of whom 95 were admitted to hospital because of jaundice, 22 developed jaundice while in hospital, and four remained in the community. Causes of jaundice were: malignancy 42, sepsis/ shock 27, cirrhosis 25, gall stones 16, drugs 7, autoimmune hepatitis 2, and viral hepatitis 2. One in five was wrongly diagnosed, often as viral hepatitis. Although 30% were under surgical care only 4% required surgery. Overall mortality was high (31%) and greatest in sepsis/ shock (51%). Gastroenterologists and GPs both perceived malignancy and gall stones to be the commonest causes of marked jaundice followed by viral hepatitis and cirrhosis; sepsis/shock was hardly mentioned. Conclusions-There are important discrepancies between gastroenterologists' and GPs' perceptions of likely causes of jaundice and the actual causes we have shown. In particular, sepsis/shock is common in hospital practice but is overlooked whereas viral hepatitis is rare but perceived as common and overdiagnosed. Gall stones usually cause mild jaundice with bilirubin levels less than 120 µmol/l. Many patients are referred to surgical services for historical reasons yet rarely require surgery and are usually treated by physicians or endoscopists. (Gut 2001;48:409-413)
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