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.
Ptc(co(2)) recording in patients on PCA-morphine and supplemental oxygen revealed hypercapnia in the presence of normal respiratory rates and Sp(o(2)) values. This is recommended as an easy and sensitive monitor of respiratory depression and may have a role in the safe administration of opioid-analgesia.
ObjectivesTo analyse the perioperative and oncological outcomes of all radical prostatectomies (RPs) performed for high-risk prostate cancer in the British Association of Urological Surgeons (BAUS) national registry from 2014 to 2015. Patients and MethodsWe identified and analysed outcomes of all RPs performed for high-risk prostate cancer (clinical stage >T2 and/or biopsy Gleason grade >7 and/or preoperative prostate-specific antigen level ≥20 ng/mL) in the national registry for 2014 and 2015. Surgeon reporting of data was mandated during this period. Institution and individual surgeon volumeoutcome relationships were assessed. ResultsIn total, 3671/13 947 (26.3%) patients underwent RP for high-risk prostate cancer over the 2-year period. Robotassisted RP was the most prevalent approach (60.7%). In all, 39% of men received an extended pelvic lymph node dissection (LND), but over one-third (33.8%) had no LND. Minimally invasive techniques were associated with a significantly shorter length of stay. The reported rates of Clavien-Dindo ≥III complications within the dataset were low (2.0%), regardless of surgical modality or surgeon volume. No statistically significant surgeon volume-outcome relationships were identified when surgeon volume was stratified into tertiles. ConclusionRP for high-risk prostate cancer in the UK appears safe, regardless of modality used or surgeon volume. No clear evidence that surgeon volume impacts on early perioperative outcomes was seen. Quality assurance of the surgeon-reported BAUS dataset is now required to drive quality improvement in national practice.
LBA4008 Background: Esophageal adenocarcinoma (EA) is the sixth most common cause of global cancer death. We rely on endoscopy screening to identify and monitor patients with Barrett’s esophagus (BE) and find neoplastic lesions early enough to manage their EA. This approach has a modest effect on EA supported by low quality evidence. We evaluated the efficacy of aspirin and high dose acid suppression in preventing EA in patients with BE. Methods: We recruited patients with ≥ 1cm of BE and no high grade dysplasia (HGD) or EA at baseline in UK and Canadian hospitals. To conceal allocation, a central trials unit randomized patients using a computer-generated schedule. Patients were randomized unblinded 1:1:1:1 in a 2X2 factorial design to high dose (40mg twice daily) or low dose (20mg once daily) esomeprazole proton pump inhibitor acid suppression (PPI), alone or combined with low dose aspirin 300mg/day (330mg in Canada). The primary composite endpoint was time to all-cause mortality or EA or HGD analyzed using accelerated failure time modelling adjusting for minimization factors (age, length of Barrett’s esophagus and presence of intestinal metaplasia). Results: We recruited 2563 Barrett’s patients followed-up for a median of 8.9 years (interquartile range 8.2-9.8) with 20,095 years of follow up. There were 313 events of the composite primary endpoint. High dose PPI was statistically significantly superior to low dose PPI (p = 0.037, N = 2535, time ratio (TR) 1.27, 95% CI = 1.01-1.58). Aspirin therapy showed a trend to benefit but was not statistically significant (p = 0.068, N = 2280, TR = 1.24, 95% CI = 0.98 – 1.57). The combination of aspirin with high dose PPI had the strongest effect compared to low dose PPI with no aspirin (TR = 1.59, 95% CI = 1.14 to 2.23, p = 0.007). There were few serious adverse events reported (1.0% of patients), with 99.9% data collected. Conclusions: This is the largest randomized controlled chemoprevention trial in patients with Barrett’s esophagus. We have shown that PPI high dose and aspirin chemoprevention therapy, especially in combination significantly reduces rates of death, EA or HGD occurrence and is safe. Clinical trial information: 2004-003836-77.
IntroductionWe prescribe medicines to patients but the key factor determining efficacy is the dose taken. Recent evidence suggests compliance with aspirin therapy is vital to ensuring its chemoprevention efficacy. Therefore we look at the patient’s compliance with aspirin in a large trial.MethodIn the 2 × 2 factorial AspECT study, Barrett’s patients were randomised to take 300 mg Aspirin daily or no aspirin and to take 20 mg or 80 mg of PPI. This paper describes for the first 5 years after randomisation the aspirin taking pattern of those prescribed aspirin. Logistic regression analysis was used to consider what factors affected compliance.ResultsOf the 1116 patients randomised to aspirin, 803 (72%; 95% CI 69.2, 74.5) took aspirin for 5 years or until discontinuation related to the trial. Of the 803, 514 took aspirin at a dose of 300 mg and 77 took a lower dose for 5 years without interruption (150 mg (38), 75 mg (24), 150 mg later reducing to 75 mg (15)). The remaining 212/803 had interruptions as permitted in the protocol or discontinued due to trial related reasons (e.g. trial endpoints or protocol deviations).There was no evidence to suggest that gender, dose of PPI, age, ethnicity or length of Barrett’s predicted 5 year compliance.ConclusionConclusion: In AspECT, 72% of patients were compliant with aspirin for 5 years or until discontinuation related to the trial. We did not discover any features predicting compliance. However since all patients were randomised to PPI, it does indicate longer term aspirin chemoprevention may be limited in over a quarter of the reflux population.Our thanks to the patients and the sites.The trial is sponsored by the University of Oxford with grant funding from CR-UK (A4584) and support from the Investigator-Sponsored Study Program of AstraZenecaTrial management and statistics provided by OCTO (OCTRU) and CSMDisclosure of InterestNone Declared
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