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Typical reflux symptoms and oesophagitis are as frequent in southern as in northern Europe
Gastro-oesophageal reflux disease (GORD) and its complications account for a significant part of the workload for gastroenterologists, surgeons and primary care physicians. However, the knowledge about reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population is limited. In this issue Zagari et al present a population-based study including endoscopy, assessment of reflux symptoms, potential risk factors and various demographic factors in 1033 subjects living in two villages in northern Italy. The prevalence of reflux symptoms was 44.3%, and 23.7% of the population experienced frequent symptoms, that is at least 2 days per week. The prevalence rates of oesophagitis and Barrett’s oesophagus in the population were 11.8% and 1.3%, respectively. Reflux symptoms were associated with the presence of oesophagitis (see fig), but interestingly enough no reflux symptoms were reported by 32.8% of individuals with oesophagitis and 46.2% of those with Barrett’s oesophagus. Hiatus hernia, but surprisingly not body mass index, was associated with reflux symptoms, oesophagitis and Barrett’s oesophagus. Studies like this one are needed to better understand the generation of reflux symptoms and risk factors for the development of complications to GORD. See p 1354
Metabolic syndrome and visceral obesity are risk factors for reflux oesophagitis
It is generally accepted that obesity is associated with GORD and abdominal obesity seems to be more important than general obesity. Chung et al convincingly demonstrate that metabolic syndrome is associated with reflux oesophagitis and that abdominal obesity, especially visceral obesity, is an important risk factor for reflux oesophagitis. This was done in a large cross-sectional study including 7078 patients undergoing upper endoscopy during health check-ups (3539 patients with reflux oesophagitis vs age- and sex-matched controls). In a subset of the patients (750 cases and controls) visceral and subcutaneous tissue was measured using abdominal CT scan. Metabolic syndrome was associated with reflux oesophagitis (see table) and among the individual components of metabolic syndrome, waist circumference and triglyceride levels independently increased the risk for reflux oesophagitis. Visceral adipose tissue area was an independent risk factor for reflux oesophagitis after adjusting for multiple confounding factors. Avoiding weight gain and accompanying metabolic syndrome seems to be associated with a lower risk of GORD and is therefore worth striving for. See p 1360
Bile acids dilate intercellular spaces and weaken barrier function of oesophageal mucosa
Although proton-pump inhibitors can control acid reflux extremely well they are not so effective in controlling reflux of duodenal contents containing both bile and pancreatic enzymes that may be responsible for both symptoms and Barrett’s metaplasia. Recent studies emphasise the importance of dilated intercellular spaces in the oesophageal mucosa which allow access of noxious luminal agents to nociceptors, thereby signalling heartburn. The study examined the effect of various concentrations of bile acid and the effect of pH on the injurious effect of bile. Low-dose bile acids increased permeability of the mucosa when exposed to acidic solutions and weakly acidic solutions (pH 5.0), which account for a substantial proportion of all reflux events that occur postprandially when gastric acid is often buffered by food. At pH 5 bile acids at 2 mmol/l and 5 mmol/l concentration significantly increased mucosal permeability (see fig) and dilated the intercellular spaces. Such changes could account for some of the reflux symptoms which persist despite proton-pump-inhibitor treatment. See p 1366
Peptic ulcer and Helicobacter pylori: are reduced T regulatory cells to blame?
Infection with cagA positive strains of Helicobacter pylori is well known as a cause of peptic ulcer, but in most cases the usual outcome of H Pylori infection is asymptomatic gastritis. The normal persistence of low-level asymptomatic infection appears in part due to the inhibitory effect on the immune response exerted by the abundant T regulatory cells (Treg) which are induced by H pylori. This study examined the response of Treg cells isolated from gastric biopsies and analysed by fluorescent activated cell sorting. Compared with uninfected controls, patients with H pylori showed increased interferon-γ, interleukin (IL)-4 and IL-10 production when stimulated with H pylori antigen. When H pylori-infected biopsies from individuals with and without peptic ulcer were compared, peptic ulcer was associated with a 22-fold reduction in mRNA for IL-10 and a 5fold reduction in FOXP3 mRNA, a marker of Treg cells (see fig). Finally, in vitro work using human gastric epithelial cells co-cultured with H pylori showed that exogenous IL-10 inhibits interleukin-8 production and the production of the pro-inflammatory transcription factor NFκB. The authors conclude that an effective Treg response to H pylori infection may protect against inflammation and peptic ulcer. See p 1375
No benefit of narrow band imaging compared with white light colonoscopy to detect colonic neoplasms
Advances in colonoscope design and colonoscopy techniques are leading to continuous improvements in rates of neoplasm detection. One recent technological advance, narrow band imaging (NBI) excludes the red end of light spectrum so that the vasculature appears dark, thus enhancing the contrast between normal and abnormal tissue. In order to compare this with traditional white light (WL) imaging six experienced endoscopists performed back-to-back colonoscopy in 276 individuals, 47% of whom had polyps detected. Patients with inflammatory bowel disease or polyposis syndrome were excluded. One hundred and thirty-five individuals underwent NBI first followed by WL and 141 had two WL examinations. There was no difference in miss rate, calculated as the difference between the first and second examination (see table). Most of the missed adenomas were <5 mm and miss rate for neoplasms > 10 mm was just 0.7 and 0%, respectively. Prior to the initiation of the study there was extensive training and optimisation of the endoscopy system. Althouh NBI improves contrast, the recent advances in conventional WL imaging appears to have removed any advantage of NBI in this particular patient group. See p 1406
Adiponectin: a protective factor against acute pancreatitis
Obesity is a risk factor for the development of severe acute pancreatitis, but the mechanism behind this is unclear. Reduced plasma levels of adiponectin, an adipose tissue-derived secretory factor, are observed in obese patients and are associated with several obesity-related disorders. Moreover, adiponectin has anti-inflammatory properties. Therefore, the involvement of adiponectin in the development of severe acute pancreatitis seems plausible. This is supported by the findings in the study by Araki and colleagues, where adinopectin-knockout mice but not wild-type mice, fed a high fat diet and then treated with caerulein developed pancreatic damage and inflammation (see fig). Furthermore, adenovirus-mediated over-expression of adiponectin attenuated the severity of acute pancreatitis induced by the same protocol in adiponectin-knockout mice, but had no effect in wild-type mice. Taken together these findings support the hypothesis that adiponectin might be one of the mediating factors explaining why obesity is a risk factor for acute pancreatitis. Prospective studies evaluating the effect of adiponectin on acute pancreatitis in humans are now needed. See p 1431
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