Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 20-30% of patients with gastro-oesophageal reflux symptoms report inadequate symptom relief while on PPI therapy. Persisting acid or non-acid reflux can be demonstrated in 40-50% of them suggesting that there is room for anti-reflux therapy in these patients. New anti-reflux compounds aim at decreasing the occurrence of transient lower oesophageal sphincter relaxations (TLOSRs) which represent the main mechanism of all types of reflux. The most promising classes of compounds are GABA(B) agonists and mGluR5 antagonists which have been shown to reduce both reflux episodes and symptoms and are currently under evaluation in phase II and III clinical trials. Compounds that target TLOSR activity represent a promising new therapeutic option for patients who suffer from GORD symptoms. These drugs will probably be developed as add-on therapy in combination with PPIs provided the tolerability and safety issues are resolved.
Best Pract Res Clin Gastroenterol 2010 Dec
PMID:Medical treatment of GORD. Emerging therapeutic targets and concepts. 2112 5

Apart from typical reflux symptoms and oesophagitis, the clinical presentation of GERD can be dominated by mucosal complications of reflux (Barrett's oesophagus, oesophageal adenocarcinoma, Peptic structure) or by extra-oesophageal syndromes, most notably asthma, laryngitis, or chronic cough. Managing these entities is much less straightforward than with oesophagitis. With respect to adenocarcinoma, metaplasia and dysplasia are recognised precursors, but the potential of these lesions to evolve to cancer has not been shown to lessen as a result of treatment, medical or surgical. Consequently, management focuses on strategies to identify and eliminate high-grade dysplasia and intramucosal cancer, lesions that are potentially curable by endoscopic ablation or surgical resection. With respect to the extra-oesophageal GERD syndromes, these are increasingly recognised as multifactorial conditions with reflux as an exacerbating factor. Treatment trials have been generally disappointing and the clinical challenge remains in accurately identifying afflicted patients who might benefit from more intensive medical or surgical reflux treatment.
Best Pract Res Clin Gastroenterol 2010 Dec
PMID:Treatment of GERD complications (Barrett's, peptic stricture) and extra-oesophageal syndromes. 2112 7

Due to its large prevalence, gastro-oesophageal reflux disease is an ideal target for companies developing medical devices designed to cure reflux. Indeed, because medications leave part of the patients unsatisfied, there is a potential place for alternative therapies, capable of restoring an efficacious anti-reflux barrier, but without the drawbacks of surgery. For more than a decade, several novel endoluminal therapies were developed, clinically evaluated, put on the market and, for many of them, withdrawn due to economic considerations, lack of efficacy or complications. These therapies were designed to act on the gastro-oesophageal junction and reinforce mechanically the anti-reflux barrier by three different ways: suturing, radiofrequency energy application, or implantation of foreign materials. Most of the published data come from open uncontrolled studies with short-term enthusiastic results. There are a few randomized control trials assessing the true efficacy of these modalities, showing often less impressive results than the open studies did, due to a high placebo effect in mild gastro-oesophageal reflux disease. Although endoscopic treatment of gastro-oesophageal disease is still an interesting topic of investigation, one can draw some lessons from the recent experiences and foresee which place these techniques could find in the management of patients suffering from reflux.
Best Pract Res Clin Gastroenterol 2010 Dec
PMID:Ensocopic-endoluminal therapies. A critical appraisal. 2112 8

Barrett's oesophagus normally affects the distal oesophagus when metaplastic columnar lined epithelium replaces stratified squamous epithelium which predisposes to cancer development. This develops as a consequence of chronic gastroesophageal reflux (GORD). Those with Barrett's have a 40 fold increased risk of oesophageal adenocarcinoma [1]. There are is still a lack of understanding of the natural history of the cell of origin. This does hamper research into this area. We accept that there is a limitation in testing of the pathogenesis of Barrett's oesophagus due to a lack of a universally accepted animal model. The major questions surrounding Barrett's oesophagus include validity of surveillance strategies, the optimal treatment and more importantly an agent that can prevent progression to cancer without unacceptable side effects. The main chemopreventative agents that show promise are aspirin and proton pump inhibitors (PPIs). There are other agents such as green tea, berries and antioxidants and diet that have been suggested; we discuss the evidence available for these strategies. We hope for continued improvement in the clinical trial infrastructure to facilitate testing of new pharmacological and endoscopic interventions for Barrett's oesophagus.
Best Pract Res Clin Gastroenterol 2011 Aug
PMID:Chemoprevention in Barrett's oesophagus. 2212 72

Gastro-oesophageal reflux disease (GORD) occurs when reflux of gastric contents causes troublesome symptoms and/or complications (the Montreal definition). GORD is a common condition with a substantial economical burden to the community and it has a significant negative effect on health-related quality of life (HRQoL) while endoscopic findings like erosive oesophagitis per se seem to correlate badly with the experienced HRQoL. The prevalence of GORD varies over the world for unknown reasons, but genetic differences, difference in the Helicobacter pylori prevalence and life style factors like obesity might influence. The prevalence is lowest in East Asia (2.5-9.4%) and higher in Mid (7.6-19.4%) and Western Asia (12.5-27.6%). The highest population-based prevalence is reported from Europe (23.7%) and the US (28.8%). GORD seems to be fairly stable over time both in terms of symptoms and erosive oesophagitis, but the prevalence seems to be increasing both in Asia and in the West.
Best Pract Res Clin Gastroenterol 2013 Jun
PMID:Epidemiology of reflux symptoms and GORD. 2399 72

In gastroesophageal reflux disease (GERD) symptoms arise due to reflux of gastric content into the oesophagus. However, the relation between magnitude and onset of reflux and symptom generation in GERD patients is far from simple; gastroesophageal reflux occurs several times a day in everyone and the majority of reflux episodes remains asymptomatic. This review aims to address the question how reflux causes symptoms, focussing on factors leading to enhanced reflux perception. We will highlight esophageal sensitivity variance between subtypes of GERD, which is influenced by peripheral sensitization of primary afferents, central sensitization of spinal dorsal horn neurons, impaired mucosal barrier function and genetic factors. We will also discuss the contribution of specific refluxate characteristics to reflux perception, including acidity, and the role of bile, pepsin and gas and proximal extent. Further understanding of reflux perception might improve GERD treatment, especially in current partial responders to therapy.
Best Pract Res Clin Gastroenterol 2013 Jun
PMID:How reflux causes symptoms: reflux perception in gastroesophageal reflux disease. 2399 74

The diagnosis of GERD in primary care settings can be enhanced by the use of structured questionnaires that suggest a high probability of GERD. Clinical outcomes can be improved and costs reduced by adopting this strategy. Using predominant symptoms to determine the path of treatment or the use of an empirical test of proton pump inhibitors has not been proven to be reliable and should be abandoned.
Best Pract Res Clin Gastroenterol 2013 Jun
PMID:The initial diagnosis of GERD. 2399 75

Gastroesophageal reflux disease (GERD) is a diagnosis applicable to "all individuals who are exposed to the risk of physical complications from gastroesophageal reflux, or who experience clinically significant impairment of health related well being (quality of life) due to reflux related symptoms, after adequate reassurance of the benign nature of their symptoms". It remains, predominantly, a symptom-based diagnosis, confirmed clinically by a response to acid suppression therapy although it is accompanied by demonstrable increases in acid exposure on esophageal pH-metry and by endoscopic and histological changes. Standard white light endoscopy permits diagnosis of erosive reflux disease (ERD) which, if present, should be graded for severity using the Los Angeles classification system. However, the role of endoscopy in clinical practice is, primarily, to evaluate patients with persistent symptoms, despite medical therapy, or to investigate alarm features and exclude complications such as Barrett' oesophagus which should be assessed using the Prague C & M criteria. Newer endoscopic techniques allow detection of 'minimal change' GERD lesions and Barrett's oesophagus-associated dysplastic or neoplastic lesions; however, none of the newer techniques has been validated for routine clinical practice. There is an increasing recognition that histology in GERD may provide useful diagnostic information, in part to exclude other lesions, such as eosinophilic oesophagitis, intestinal metaplasia and dysplasia or malignancy and, in part, to identify changes, such as basal cell hyperplasia, papillary elongation and, most recently, dilated intercellular spaces, that are consistent with GERD. However, more widespread incorporation of histology into the clinical management of GERD will require a standardized biopsy protocol and efforts to minimise interobserver differences in the identification of GERD-related histological changes.
Best Pract Res Clin Gastroenterol 2013 Jun
PMID:What is the role of endoscopy and oesophageal biopsies in the management of GERD? 2399 76

Gastro-oesophageal reflux disease develops when the reflux of gastric contents into the oesophagus results in troublesome symptoms and/or complications [1]. Refluxate contains predominantly acid which causes tissue injury at oesophageal and extra-oesophageal sites. It is one of the commonest gastrointestinal diagnosis worlds over. It is associated with chronic symptoms, reduced QOL, significant cost and serious complications. Goals of therapy are to provide symptom relief, heal oesophagitis and prevent long-term complications. Therapeutic measures are directed at reducing the noxiousness of the refluxate; reducing the gastro-oesophageal reflux; enhancing clearance; protecting the mucosa; reducing the mucosal sensitivity and improving healing. Acid suppression with proton pump inhibitors remains the cornerstone of therapy. Recent studies have resulted in better understanding of disease and relative efficacies of various strategies. This has paved way for a better evidence based approach. The therapy however needs to be individualized depending upon the clinical profile, disease severity, the dominant pathophysiological mechanism, cost, availability and individual preferences.
Best Pract Res Clin Gastroenterol 2013 Jun
PMID:Management of reflux-related symptoms. 2399 77

Proton pump inhibitors (PPIs) remove most of the acid from the gastroesophageal refluxate. However, PPIs do not eliminate reflux and the response of specific GERD symptoms to PPI therapy depends on the degree to which acid drives those symptoms. PPIs are progressively less effective for heartburn, regurgitation, chest pain and extra-oesophageal symptoms. Hence, with an incomplete PPI response, obtaining an accurate history, detailing which symptoms are 'refractory' and exactly what evidence exists linking these symptoms to GERD is paramount. Reflux can continue to cause symptoms despite PPI therapy because of persistent acid reflux or weakly acidic reflux. Given these possibilities, diagnostic testing (pH or pH-impedance monitoring) becomes essential. Antireflux surgery is an alternative in patients if a clear relationship is established between persistent symptoms, particularly regurgitation, and reflux. Treating visceral hypersensitivity may also benefit the subset of GERD patients whose symptoms are driven by this mechanism.
Best Pract Res Clin Gastroenterol 2013 Jun
PMID:Management of the patient with incomplete response to PPI therapy. 2399 78


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