Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial.

BACKGROUND: Oesophageal 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. METHODS: The 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. FINDINGS: Between 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. INTERPRETATION: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus. FUNDING: Cancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

Perioperative and oncological outcomes of radical prostatectomy for high-risk prostate cancer in the UK: an analysis of surgeon-reported data.

OBJECTIVES: To 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 METHODS: We 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 volume-outcome relationships were assessed. RESULTS: In total, 3671/13 947 (26.3%) patients underwent RP for high-risk prostate cancer over the 2-year period. Robot-assisted 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. CONCLUSION: RP 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.

Normal nerve striations are altered in the trembler-J mouse, a model of Charcot-Marie-Tooth disease.

INTRODUCTION: This study was initiated because it was noted that the peripheral nerves of Trembler-J mice (a model of human Charcot-Marie-Tooth disease) appear to lack normal striations. METHODS: We performed confocal microscopy of whole sciatic nerves and tested the effect of axial stress on impulse conduction. RESULTS: We found that the axons of mutant mice were longer than those of the wild-type (1.55 mm of axon/mm length of nerve vs. 1.28 mm/mm respectively). This axonal elongation altered the helical nerve striations (bands of Fontana). As nerves were stretched axially, the conduction distance became correspondingly shorter. The effect on latency was significantly greater in the more coiled nerves of Trembler-J mice (P = 0.038). CONCLUSIONS: The finding that mice with a mutated peripheral myelin protein 22 (PMP22) possess excessively long axons may be related to the excess Schwann cell numbers found in this disorder.