Adam, Eve and the reflux enigma: age and sex differences across the gastro-oesophageal reflux spectrum.

INTRODUCTION: We present demographic differences across the gastro-oesophageal reflux disease (GORD) spectrum in a UK District General Hospital. PATIENTS AND METHODS: Data were prospectively collected over 37 years. At endoscopy patients were categorized as: erosive oesophagitis (EO), Barrett's oesophagus (BO) or nonerosive reflux disease (NER). Analysis 1: comparison of EO, BO and NER 1977-2001 when the database for GORD without BO closed. Analysis 2: demographic differences in oesophageal adenocarcinoma (OAC) in total BO population diagnosed 1977-2011. RESULTS: GORD 1977-2001 (n=11 944): sex, male predominance in EO and BO but not NER; male : female ratios, 1.81, 1.65, 0.87, respectively (P<0.0001); mean age at presentation, EO 54 years, BO 62 years, NER 50 years; women were older than men by 10, 7 and 6 years, respectively.BO 1977-2011: prevalent OAC, 87/1468 (6%); male : female ratio, 4.1 (P<0.0001); incident OAC, 54/1381 (3.9%); male : female ratio, 3.5 (P<0.0001). Among all BO, more men developed OAC (3 vs. 0.9%). Within each sex, proportion of OAC higher among men (4.9 vs. 2.3%); at OAC diagnosis women were slightly but not significantly older (69.9 vs. 72.3 years, P=0.322). CONCLUSION: Two views may explain our findings. First, women have either milder reflux, or reduced mucosal sensitivity hence reflux remains silent for longer. Alternatively, women genuinely develop reflux later, that is, are more protected and for longer from developing GORD and its complications. Early evidence is emerging that female sex hormones may indeed have a protective role in GORD during the reproductive period. We suggest reflux and its consequences may be an example of 'protection' conferred on Eve.

The evolution and outcome of surveillance of Barrett's oesophagus over four decades in a UK District General Hospital.

INTRODUCTION: We present the long-term outcome of Barrett's oesophagus (BO) at a District General Hospital set against the increasing numbers of patients with gastro-oesophageal reflux disease (GORD). METHODS: Data were collected prospectively over 37 years. Comparison of GORD without Barrett's (NoBO) versus BO was performed from 1/1/1977 to 31/12/2001 when the NoBO database closed and outcomes of all cases of BO diagnosed until 31/12/2011 and followed up until 31/12/2013 have been reported. RESULTS: During the period 1977-2001 the number of GORD NoBO cases was 11 610, and that of BO cases was 764 (6.2% of all GORD); total number of BO cases in 1977-2011 was 1468. NoBO patients were younger than BO patients: 52.2 versus 61.6 years. There was a male predominance in both groups: NoBO 55% and BO 62% (P<0.0001). The prevalence of oesophageal adenocarcinoma (OAC) was 87/1468 (5.9%) BO cases. Its incidence was 54/1381 (3.9%); the mean interval between the diagnosis of BO and incident OAC was 9 years (range 13 months-25.4 years); there was one OAC per 192 patient-years of follow-up (0.52% per year). Mortality was significantly lower in 37 patients under endoscopic surveillance at the time OAC was diagnosed (51 vs. 88% P=0.0141) partly because of older age and comorbidity of the other 17, in whom serial endoscopy was contraindicated. A proportional hazards model to allow for age estimated that the hazard rate ratio was lower in the surveillance group; however, this difference did not reach statistical significance (0.64, 95% confidence interval 0.30-1.48, P=0.08). Excluding prevalent cancers from both groups, mortality in BO was double that in NoBO (47 vs. 24%). CONCLUSION: These 37 years of observation suggest, but do not confirm, that endoscopic surveillance may reduce the risk of death from OAC. Modern technology is likely to yield better results, but larger prospective studies are needed to confirm the benefits.

The socioeconomic profile of a Barrett's oesophagus cohort assessed by the 2010 Index of Multiple Deprivation.

BACKGROUND: Several reports have described the relationship between socioeconomic status and oesophageal adenocarcinoma but only one with its precursor condition, Barrett's oesophagus. We therefore investigated such an association. PATIENTS: The majority (88%) of patients diagnosed with Barrett's at Rotherham District General Hospital between 28 April 1978 and 31 August 2012 consented to inclusion in the UK Barrett's Oesophagus Registry. Those residing within Rotherham form the basis of this study. METHODS: We assessed socioeconomic status using the Index of Multiple Deprivation 2010 scores which can be assigned to every English postcode. The scores for the whole of England were divided into five equal groups; those of the 6257 postcodes within Rotherham (including those of Barrett's patients) were compared against the national quintile relevant to their score. We examined the ratio of observed against expected numbers of Barrett's in each quintile before and since 2001, the median year of diagnosis. RESULTS: The study group comprised 1076 patients with Barrett's oesophagus. Before 2001 their distribution across the deprivation quintiles was similar to that expected. Since then it has changed significantly, with 37% more Barrett's patients than expected among the two least deprived quintiles, but 11% fewer than expected in the larger population comprising the two most deprived quintiles (P=0.0001). There was no significant difference in the distribution of sex (P=0.27), nor the mean age at diagnosis between the two time periods (P=0.92). CONCLUSION: Since 2001, there has been a major change in the distribution of Barrett's in relation to socioeconomic status, measured by the Index of Multiple Deprivation.

Barrett's, blood groups and progression to oesophageal cancer: is nitric oxide the link?

INTRODUCTION: Incidence of oesophageal adenocarcinoma (OAC) is increasing rapidly. OAC arises in columnar-lined oesophagus (CLO), a metaplastic change affecting some patients with gastro-oesophageal reflux disease (GORD). As yet there is no reliable method of identifying those at highest risk. Our earlier observation of an association between OAC and blood group O Rhesus negative, if confirmed, may help identify those at greatest risk. AIM AND METHODS: To assess the distribution of blood group and Rhesus D (RhD) factor in patients with GORD compared with the blood donating general population. GORD was categorized as nonerosive reflux (NER), erosive oesophagitis, CLO and OAC. The Rotherham Hospital database holds details of all GORD, CLO and OAC patients seen in the Gastroenterology Unit. Blood group information for patients with GORD was obtained from patients' records and the hospital's blood transfusion service. The blood group distribution in the general population was obtained from the National Blood Transfusion Service. The number of expected to observed patients in each blood group for each subtype was compared. RESULTS: Two thousand six hundred and ten NER, 2813 erosive oesophagitis, 568 CLO and 73 OAC patients had a recorded blood group. For RhD positive patients observed proportions in each blood group were similar to expected. The most striking difference was the marked excess of OAC in blood group O, Rhesus negative (P=0.002). CONCLUSION: CLO patients with blood group O, RhD negative carry a disproportionately higher risk of developing OAC. The mechanism is unknown but the finding has practical application in guiding risk stratification and intensity of surveillance.