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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastroesophageal reflux disease (GERD) is a common clinical problem. Circumstantial evidence continues to suggest that infection with Helicobacter pylori may protect some patients from developing GERD and its complications. An empirical trial of a proton-pump inhibitor may now be a reasonable alternative to endoscopy or 24-hour pH testing for the diagnosis of GERD. Long-term follow-up data covering more than over a decade indicate that proton-pump inhibitors are effective and safe agents for the treatment of GERD. Furthermore, a strategy of proton-pump inhibitors first may be the most cost-effective approach to GERD. It remains unclear why some patients with GERD develop Barrett's esophagus, whereas others do not. Recent studies demonstrate the importance of pulses of acid or bile in increasing cell proliferation and cyclooxygenase-2 expression in Barrett's epithelium cell cultures. Short-segment Barrett's esophagus is now clearly associated with an increased risk of dysplasia or cancer compared to intestinal metaplasia of the cardia, and the cancer risk in this condition is similar to that with long-segment Barrett's esophagus. However, the overall cancer risk in patients with Barrett's esophagus is lower than previously estimated, at approximately 0.5% annually. Ablation techniques continue to show promise, but are not yet ready for routine clinical use. Endoscopic mucosal resection is a new treatment option for selected patients with high-grade dysplasia or superficial esophageal adenocarcinoma.
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PMID:Gastroesophageal reflux disease and Barrett's esophagus. 1127 13

The development of Barrett's esophagus (BE) in patients with gastroesophageal reflux disease (GERD) is troubling because of its known association with esophageal cancer. When evaluated clinically, patients with BE have the severest form of GERD and require aggressive therapy to control esophageal acid exposure. Both hypotension of the lower esophageal sphincter and the extent of esophageal acid exposure are major contributors to severe GERD and its complications. It is hypothesized that better control of acid will improve outcomes for BE patients. While it is clear that therapy (medical or surgical) for reflux rarely if ever results in total regression of BE, there are some limited data to support improvement in BE with control of reflux. Current medical choices include prokinetic agents, histamine type-2 receptor antagonists, and proton pump inhibitors. In the future, genetic markers may be used in identifying BE patients at the greatest risk for histologic progression, and chemoprevention with cyclooxygenase-2 inhibitors may be a therapeutic option. This paper will review the rationale for and results of medical antireflux therapy in patients with BE.
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PMID:What is the optimal medical therapy for Barrett's esophagus? 1135 93

The literature on peptic ulcer and gastritis in 2000 again focused on the topics of Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), and gastric cancer. New diagnostic tests for H. pylori infection have been evaluated, and rescue therapies for failed H. pylori eradication have been tested. The causal relationship between H. pylori infection and nonulcer dyspepsia, gastric cancer, gastroesophageal reflux disease, and NSAID-related ulcers remained heated topics of debate. In 2000, landmark clinical trials and meta-analyses were published addressing these issues. The role of endoscopy in managing nonulcer dyspepsia was better defined. The role of H. pylori eradication in NSAID/aspirin users was reexamined in high-risk patients. Clinical benefit was finally confirmed for specific inhibitors of cyclooxygenase-2 (COX-2). The millennium year turned out to be a very important one in the advancement of knowledge in this field.
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PMID:Ulcer and gastritis. 1182 5

Barrett's esophagus (BE), a premalignant lesion to esophageal adenocarcinoma is associated with long-standing, gastroesophageal reflux disease (GERD). BE is a multi-phase process: during the initiation phase, genetically predisposed individuals (mostly white men) suffering from clinical or occult reflux damage their distal esophagus and form a new cell phenotype (incomplete intestinal metaplasia). During the formation phase, this phenotype occupies an area of variable surface (short or long-segment BE). During the progression phase, the metaplastic epithelium either remains dormant or progresses to dysplasia and adenocarcinoma. We review the recent clinical and basic research literature that explores the interaction of the refluxate (acid, bile, etc.) with BE. Acid and bile reflux variably affect BE and may cause dysplasia or adenocarcinoma. Regardless of the underlying biology, a patient with BE may suffer from GERD symptoms or may remain asymptomatic. Acid may be synergistic to bile or it could be antagonistic and protective. Acid suppressive therapy, if profound and continuous enough to abolish symptoms and esophageal acid exposure, may decrease proliferation, increase differentiation and reduce BE surface. Overexpression of cyclooxygenase-2 (COX-2), not entirely independent of acid/bile reflux, may increase proliferation and increase the invasiveness and metastatic potential of Barrett's metaplasia and neoplasia. Clinically, both acid and bile reflux need to be inhibited, either with potent acid-suppressing drugs or anti-reflux surgery. Cyclooxygenase inhibition using aspirin, NSAIDs or the safer COX-2 inhibitors added to these anti-reflux therapies may enhance the therapeutic benefit. Many questions remain unanswered. We still do not know why only a fraction of patients with GERD develop BE, what factors of the refluxate (acid, bile, etc.) initiate metaplasia and/or promote carcinogenesis, which patients are at risk for malignancy, and what is the best chemopreventive strategy. Ablation therapies and endoscopic mucosal resection are still under study.
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PMID:Management of Barrett's esophagus with and without dysplasia. 1279 81

Medication-induced oesophageal distress and injury have become increasingly common conditions. First, smooth muscle relaxants may worsen or produce symptoms of pre-existing gastro-oesophageal reflux disease; notable examples include certain calcium antagonists (nifedipine), nitrates, sildenafil, nicotine, theophylline, and substances with antimuscarinic potential. Second, drugs with local toxicity may produce de novo damage including inflammation, strictures, ulcers, and bleeding. Notorious examples are alendronate, certain antibiotics including tetracyclines and clindamycin, all NSAIDs/aspirin, quinidine, potassium chloride, and ferrous sulfate. Cyclooxygenase-2 inhibitors may be devoid of such toxicity, but may damage the mucosa by interfering with regenerative cell proliferation. The galenic formulation can modulate the risk of oesophageal injury. For this reason, medicines containing the same potentially toxic ingredient may be less exchangeable than commonly thought. Diagnostic gold standard is endoscopy. The best treatment is removal of the offending drug and supportive care. Prevention requires a re-appraisal of the drug's indication and adherence to guidelines of optimal drug intake including ingestion in an upright position and swallowing with enough fluid. The clinical relevance of drug-induced oesophageal injury and the feasibility of therapeutic alternatives are individually addressed.
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PMID:Medication-induced oesophageal disorders. 1294 50

Gastroesophageal reflux disease (GERD) is a very common disorder, mainly occurring in Western countries. The nonerosive form of GERD, which occurs in more than half of the patients affected, deserves particular attention. Administering symptomatic therapy without a prior endoscopic examination has become an attractive option, since it also provides diagnostic information. Proton-pump inhibitors (PPIs) have become established as the standard therapy, but new insights into the pathophysiology of the condition may lead to new treatment options using gamma-aminobutyric acid (GABA) agonists. Endoscopic therapy is still at the experimental stage and has yet to prove its value as an alternative to PPI and surgery. However, it is questionable whether antireflux surgery is more cost-effective in the longer term.[nl]Gastroenterologists are now much more aware of Barrett's esophagus than was the case a few years ago. Barrett's esophagus is a frequent finding in patients with reflux symptoms, but is a rare cause of death in affected patients. For several reasons, there is a large gap between recommendations regarding surveillance, on the one hand, and everyday practice on the other. New diagnostic procedures such as chromoendoscopy may allow better detection of premalignant and malignant alterations in metaplastic mucosa, but the safety of such techniques has been questioned. Prophylactic ablation is a debatable approach, whereas endoscopic interventions in patients with high-grade dysplasia and early adenocarcinoma are continuing to develop as attractive alternatives to esophagectomy in selected patients. It remains to be seen whether chemoprevention using cyclooxygenase-2 (COX-2) inhibitors should be carried out in high-risk patients with Barrett's esophagus, in order to prevent malignant transformation to esophageal cancer.
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PMID:Gastroesophageal reflux disease and Barrett's esophagus. 1476 7

Barrett's esophagus (BE) represents the most serious histological consequence of gastroesophageal reflux disease (GERD) that develops in 5-10% of patients with GERD. Given that BE is the only known precursor to esophageal adenocarcinoma (EA), a systematic endoscopic biopsy protocol can detect EAs at an early stage. However, endoscopic and histopathological evaluation of BE are not adequate for effective screening of high risk patients. Therefore, molecular abnormalities associated with BE have been considered as surrogate markers and their use as such is proposed. Flow cytometry is the most useful adjunct to histology, and ploidy status of BE is an independent risk factor. Cyclin D1 overexpression is inversely correlated with survival in EA. C-erbB2 (+) patients have poorer prognosis. High plasma adenomatous polyposis coli levels correlate with reduced patient survival. p53 expression allows patient risk for EA stratification. Nuclear factor-kappaB overexpression inversely correlates with good response to adjuvant chemotherapy and radiotherapy in EA. Patients with cyclooxygenase-2 overexpression have reduced survival rates. Increased E-cadherin staining is associated with shorter survival in EA patients who received chemoradiotherapy. Finally, existing data cannot rule out a correlation between EA and colorectal tumors. Seventeen BE molecular alterations yielded noteworthy clinical implications. Apart from endoscopy and histology, these data allow for better risk stratification for patients with BE and for more efficient and timely therapeutic approaches.
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PMID:New molecular concepts of Barrett's esophagus: clinical implications and biomarkers. 1585 73

The present paper is an update to and extension of the previous systematic review on the primary care management of patients with uninvestigated dyspepsia (UD). The original publication of the clinical management tool focused on the initial four- to eight-week assessment of UD. This update is based on new data from systematic reviews and clinical trials relevant to UD. There is now direct clinical evidence supporting a test-and-treat approach in patients with nondominant heartburn dyspepsia symptoms, and head-to-head comparisons show that use of a proton pump inhibitor is superior to the use of H2-receptor antagonists (H2RAs) in the initial treatment of Helicobacter pylori-negative dyspepsia patients. Cisapride is no longer available as a treatment option and evidence for other prokinetic agents is lacking. In patients with long-standing heartburn-dominant (ie, gastroesophageal reflux disease) and nonheartburn-dominant dyspepsia, a once-in-a-lifetime endoscopy is recommended. Endoscopy should also be considered in patients with new-onset dyspepsia that develops after the age of 50 years. Conventional nonsteroidal anti-inflammatory drugs, acetylsalicylic acid and cyclooxygenase-2-selective inhibitors can all cause dyspepsia. If their use cannot be discontinued, cotherapy with either a proton pump inhibitor, misoprostol or high-dose H2RAs is recommended, although the evidence is based on ulcer data and not dyspepsia data. In patients with nonheartburn-dominant dyspepsia, noninvasive testing for H pylori should be performed and treatment given if positive. When starting nonsteroidal anti-inflammatory drugs for a prolonged course, testing and treatment with H2RAs are advised if patients have a history of previous ulcers or ulcer bleeding.
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PMID:Evidence-based recommendations for short- and long-term management of uninvestigated dyspepsia in primary care: an update of the Canadian Dyspepsia Working Group (CanDys) clinical management tool. 1591 44

Functional oesophageal epithelial defense, including cell proliferation, restitution, buffers and ion transporters, plays a significant role in maintaining mucosal integrity and enabling rapid repair after injury. Growth factors such as epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) are associated with oesophageal epithelial proliferation or restitution. Na+/H+ exchanger-1, an ion transporter, regulates intracellular pH and cell volume, and may have roles in cell proliferation, migration and survival. Cytokine, adhesion molecules, cyclooxygenase-2 and free radicals are associated with oesophageal inflammation and breach of the functional epithelial defense. Although the oesophagus does not have strong functional epithelial defense against acid, this defensive mechanisms may be involved in the pathogenesis of non-erosive gastro-oesophageal reflux disease. Medical therapy may be developed in future to enhance functional oesophageal epithelial defense.
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PMID:Functional oesophageal epithelial defense against acid. 1625 24

Gastroesophageal reflux disease (GERD) is a common chronic disorder affecting millions of people worldwide. This is a review of a number of published studies in the past year that increase current understanding or raise important issues about this disorder. Among the areas covered are the epidemiology and role of genetics in GERD; its pathogenesis with respect to duodenogastric reflux and impaired epithelial barrier function; the effects of atropine on transient lower esophageal sphincter relaxations; the role of acid suppression, heat shock proteins, and the enzyme cyclooxygenase-2 in Barrett esophagus and esophageal adenocarcinoma; the complication rates in laparoscopic fundoplication; and the results of ablation therapy for the treatment of Barrett esophagus and esophageal adenocarcinoma. These investigations reinforce a sense of the complexity of GERD and provide optimism that modern technology will continue to be used to develop more effective treatments.
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PMID:Gastroesophageal reflux disease. 1703 Nov 1


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