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)

Gastrointestinal malignancies may be associated with obesity, defined specifically by increased body-mass index, and based largely on environmental factors rather than genetics. In particular, there seems to be a definite increase in the incidence of both oesophageal and colorectal cancer. Mechanisms associated with obesity include a particular metabolic state characterized by hyperinsulinemia, or insulin resistance, along with elevated serum leptin. Leptin is derived from adipocytes and appears to play a role in the regulation of ghrelin, a peptide derived from the stomach and small intestine that stimulates appetite and weight gain. In addition to these metabolic changes, there are other anatomical alterations that may indirectly predispose to cancer, including the predisposition of obesity to gastroesophageal reflux and, possibly, oesophageal cancer. Other mechanisms may involve adipocyte-derived cytokines, or adipokines, that may serve as signalling devices in the pathogenesis of cancer. Finally, pharmacologic and surgical avenues available for treatment of obesity, including lipase inhibitors and gastric or jejuno-ileal bypass procedures may set the stage for subsequent gastric or intestinal tract cancer.
Best Pract Res Clin Gastroenterol 2004 Dec
PMID:Risk of gastrointestinal malignancies and mechanisms of cancer development with obesity and its treatment. 1556 45

Gastroesophageal reflux disease (GERD) is highly prevalent in Western countries. It is characterized by esophageal and extra-esophageal symptoms (both typical and atypical) as well as by a number of potential complications. As the majority of patients have normal gross endoscopic findings, the assessments of symptom severity and quality of life, as well as the patients' response to treatment have become increasingly important. Self-assessed symptom questionnaires are now key instruments in clinical trials. An ideal GERD symptom questionnaire, suitable as a primary end-point for clinical trials, should: (1) be sensitive in patients with GERD, (2) cover frequency and intensity of typical and atypical GERD symptoms, (3) be multidimensional (cover all symptom dimensions), (4) have proven psychometric properties (validity, reliability and responsiveness), (5) be practical and economical, (6) be self-assessed, (7) use 'word pictures' which are easy to understand for patients, (8) respond rapidly to changes (responsiveness in short-time intervals), (9) be used daily to assess changes during and after therapy, and (10) be valid in different languages for international use. A literature review revealed five evaluative scales that met some of the above characteristics, but none fulfilled all of them. Therefore, a new evaluative tool for the assessment of GERD symptoms and their response to therapy is needed. The Reflux Questionnaire (ReQuest) is a self-assessed questionnaire developed and validated to assess the effect of treatment on the spectrum of GERD-related symptoms. Initially, GERD symptoms were identified on the basis of available literature, knowledge from previous clinical trials, experienced physicians, and patient interviews. An overall of 67 typical and atypical symptom descriptions were grouped into six different dimensions of GERD (acid complaints, upper abdominal/stomach complaints, lower abdominal/digestive complaints, nausea, sleep disturbances, other complaints). To these six dimensions a seventh, general well-being was added. Each dimension was tested by questions for frequency and intensity (except general well-being, for which only the intensity was determined). Thereafter, ReQuest was translated into different languages and tested in mother tongue patient focus groups. ReQuest psychometric properties (test-retest reliability, internal consistency, construct validity, responsiveness) were validated in two clinical trials of erosive GERD and endoscopic negative (en) GERD. In the first open, multicenter study, ReQuest was assessed in 430 patients with erosive GERD grade A-D. Patients with GERD grade A were treated with pantoprazole 20 mg od whereas those with GERD grade B-D received 40 mg od. The second open, multicenter, multinational trial with pantoprazole 20mg od assessed the ReQuest in over 800 patients with endoscopic negative GERD. Furthermore, ReQuest was used to determine the 'normal' ranges of GERD symptoms in individuals without GERD evidence. Over 300 healthy volunteers took part in a 4-day evaluation by completing ReQuest on each of the four study-days, as well as GSRS and PGWB on day 1. Based on the 90% percentiles determined in this study, a 'normal' range was calculated for ReQuest and relative subscales. The study showed that even individuals without GERD evidence can experience mild GERD symptoms. The derived 'normal' ranges within the population can be used for classification of symptom relief. In conclusion, ReQuest proved to be a valid, reliable, and responsive tool for measuring both typical and atypical GERD symptoms, and to be particularly suitable for measuring daily symptom changes and identifying normalization of the clinical picture in therapeutic trials.
Best Pract Res Clin Gastroenterol 2004
PMID:ReQuest-- the challenge of quantifying both esophageal and extra-esophageal manifestations of GERD. 1558 92

Limited available data specifically addressing nocturnal gastroesophageal reflux indicate its association with more severe injuries such as esophagitis and stricture, adenocarcinoma of the esophagus, respiratory and ENT disorders as well as sleep disturbances, diminished quality of life and undesired changes in activities of daily living. In a recent survey, altogether 79% of respondents reported experiencing heartburn at night. Among those, 75% reported that symptoms affected their sleep, 63% believed that heartburn negatively affected their ability to sleep well, and 40% believed that nocturnal heartburn impaired their ability to function the following day. Of the 791 respondents with nighttime heartburn, 71% reported taking over-the-counter medicine for it, only 29% of these rated this approach extremely effective. Forty-one percent reported trying prescription medicines and 49% of these rated this approach extremely satisfactory. This recent understanding of the prevalence and impact of nighttime heartburn is an indicator of nocturnal acid reflux events and suggests that nighttime heartburn occurs in a large majority of adults with gastroesophageal reflux disease. The fact that expected result from implemented therapy for heartburn is not achieved by a sizable percentage of patients can have significant management implications.
Best Pract Res Clin Gastroenterol 2004
PMID:Nighttime GERD: clinical implications and therapeutic challenges. 1558 93

Barrett's esophagus is a metaplastic change related to esophageal reflux of acidic gastric contents. Its presence is associated with an increased risk of adenocarcinoma. The data behind our current clinical strategies are, however, based on limited evidence. This document considers the sort of information that should be discussed with patients to allow them to make their own choices regarding therapeutic strategies.
Best Pract Res Clin Gastroenterol 2004
PMID:The challenges of Barrett's -- suppression, symptoms or surveillance. 1558 95

In the early 1900's, gastroesophageal reflux disease (GERD) was an almost unknown entity with less than 200 cases reported worldwide. Currently the disease is regarded as almost endemic with as much as 25% of the population in some countries exhibiting signs or symptoms of reflux. Early therapies directed at chemical neutralization (milk drip, antacids) were of modest effect and required constant administration for efficacy. The introduction of histamine 2 receptor antagonists in the 1970's dramatically improved the management of GERD, but was limited by problems of tachyphylaxis and adverse events. The advent of the PPI class of drugs revolutionized medical care of GERD, given their efficacy and safety profile. As a consequence, the surgical approach with its pronounced dependence on individual operator skill and its high morbidity and even mortality has fallen into disregard. Thus, modest surgical outcome results as compared to the efficacy of PPIs has led to the widespread recognition that pharmacological therapy for GERD represents the platinum standard of care and the current consensus is that the PPI class of drugs provide the safest and most effective form of therapy for GERD. Furthermore, it is apparent based on acid suppression, symptom relief and healing rates, that all PPIs are on a milligram for milligram basis similarly efficacious for the management of GERD. While a consensus exists in regard to the current management of GERD with PPIs there is little agreement as to the management of the associated mucosal metaplastic process. At this time there is inadequate understanding of the biological basis of the mucosal transformation and minimal information about the mechanistic regulation of this event and its perpetuation. A future consensus thus requires the identification of the appropriate tools to detect Barrett's early, identify the specific molecular markers associated with neoplastic transformation and establish a definitive therapeutic algorithm.
Best Pract Res Clin Gastroenterol 2004
PMID:GERD 2004: issues from the past and a consensus for the future. 1558 96

The development of proton-pump inhibitors (PPIs) caused impressive improvements in the control of gastric acid secretion. The clinically related consequences are most clearly expressed in the therapy of gastroesophageal reflux disease (GERD). Despite these glamorous outcomes, there still are unmet clinical needs. Ideally, full 24-h control of gastric acid secretion should be available to fine tune acid suppressant therapy to the individual clinical needs. Full control of acid secretion with oral PPI therapy in the presence of a healthy non-Helicobacter pylori-infected gastric mucosa is difficult, if not impossible, at present. However, there are circumstances in which full control is desirable if not essential (intensive care, esophageal columnar metaplasia, etc.). In particular, the so-called nocturnal acid breakthrough is difficult to control, particularly in patients with esophageal columnar metaplasia. But even for ordinary GERD, full symptom control and patient satisfaction is often lacking, necessating additional over-the-counter medication for control of remaining symptoms. A recent Gallup interview of 1000 symptomatic GERD patients stressed the frequency of nocturnal symptoms, insufficiently controlled with standard PPI therapy. Current PPIs are also suboptimal for 'on-demand' therapy in Non-Erosive Reflux Disease (NERD)/GERD. Moreover, rebound acid secretion after abrupt stopping of PPI therapy may favour early symptomatic relapse, necessating step-down therapy to prevent prolongation of the need of acid suppression.
Best Pract Res Clin Gastroenterol 2004
PMID:Are there unmet needs in acid suppression? 1558 97

The prevalence of upper gastrointestinal (GI) diseases is increasing in subjects aged 65 years and over. Pathophysiological changes in esophageal functions that occur with aging may, at least in part, be responsible for the high prevalence of gastro-esophageal reflux disease (GERD) in old age. GERD symptoms are different in the elderly compared to young or adult patients; moreover, esophagitis is a more severe disease in the elderly than in young subjects, relapse occurring in a high percentage of cases in those elderly patients who are not in maintenance therapy with antisecretories. In old age, PPIs are more effective than H2-blockers in healing and reducing the relapse of esophagitis; PPI therapy is well tolerated and very effective even in elderly subjects with concomitant diseases and treatments. Discontinuing maintenance treatment with PPIs after 6 months is associated with a significant increase in the relapse rate. The incidence of gastric and duodenal ulcers and their bleeding complications is increasing in old-aged populations worldwide. Approximately 53-73% of elderly peptic ulcer patients are Helicobacter pylori positive; however, the percentage of H. pylori-positive elderly patients who are treated for their infection remains very low. We now have data that demonstrate the benefit of curing H. pylori infection in elderly patients with H. pylori-associated peptic ulcer disease and severe chronic gastritis. One-week PPI-based triple therapy regimens including clarithromycin, amoxycillin and/or nitroimidazoles are highly effective and well tolerated in elderly patients. Low doses of both PPIs and clarithromycin (in combination with standard doses of amoxycillin or nitroimidazoles) are sufficient. Almost 40% of GU and 25% of DU in the elderly patients are associated with the use of NSAID and/or aspirin. Several strategies are available to prevent NSAID-related peptic ulcers, i.e. the use of low doses and/or less damaging NSAIDs, the use of coxibs, gastroprotection with antisecretory drugs, the eradication of H. pylori infection in infected patients as well as educational programs to reduce inappropriate prescriptions. Strategies for subgroups of patients that will take account of the GI and non-GI risks, i.e. disability, co-morbidity and friality of patients, according to a comprehensive geriatric assessment are recommended.
Best Pract Res Clin Gastroenterol 2004
PMID:Aging and upper gastrointestinal disorders. 1558 98

The prognosis for patients with malignancies of the gastrointestinal tract is strictly dependent on the early detection of premalignant and malignant lesions. At present, endoscopy can be performed with new, powerful high-resolution or magnifying endoscopes. Comparable to the rapid development in chip technology, the optic features of the newly designed endoscopes offer resolutions that allow new mucosal surface details to be seen. In conjunction with chromoendoscopy, the newly discovered tool of video endoscopy is much easier to use and more impressive than previously used fibreoptic endoscopy. This review summarises the value of magnifying endoscopy in the upper and lower gastrointestinal tract and focuses on gastroesophageal reflux disease and early gastric and colorectal cancer.
Best Pract Res Clin Gastroenterol 2006 Feb
PMID:Magnifying chromoendoscopy for the detection of premalignant gastrointestinal lesions. 1647 1

Current evidence indicates that cardia cancers are of at least two distinct and disparate aetiologies. One type resembles cancer of the more distal stomach (Type A), being a consequence of atrophic gastritis due to Helicobacter pylori infection or more rarely autoimmune atrophic gastritis. Another type (Type B) resembles oesophageal adenocarcinoma and is likely to be a consequence of short-segment gastro-oesophageal reflux disease. The two cancers are themselves indistinguishable but examination of the gastric phenotype indicates the aetiology: Type A occurring in patients with evidence of atrophic gastritis whereas Type B occurs in subjects with healthy acid secreting stomachs. In subjects with healthy acid secreting stomachs the cardia has a specific luminal chemistry remaining highly acidic and unbuffered following a meal and having very active nitrosative chemistry due to the acidification of nitrite in saliva. This luminal chemistry may contribute to the high incidence of metaplasia and neoplasia at this anatomical site.
Best Pract Res Clin Gastroenterol 2006
PMID:Cancer of the gastric cardia. 1699 53

Oesophageal adenocarcinoma (OA) remains one of the more deadly forms of gastro-intestinal cancer with a mortality rate exceeding 90%. The incidence of OA remains unabated and has a reported fivefold increase since 1970 [Pera M, Cameron AJ, Trastek VF, Carpenter HA & Zinsmeister AR. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 1993; 104(2): 510-513]. Gastro-oesophageal reflux disease and its sequelae, Barrett's oesophagus, is one of the principle risk factors in the development of OA, with a 30-fold increased risk in Barrett's patients compared with the general population [Tytgat GNJ. Does endoscopic surveillance in esophageal columnar metaplasia (Barrett's-Esophagus) have any real value. Endoscopy 1995; 27(1): 19-26]. OA is thought to be a microcosm of evolution, developing sequentially along the metaplasia-dysplasia-adenocarcinoma sequence. Progression is attributed to a series of genetic and epigenetic events that ultimately allow for clonal selection of Barrett's cells via subversion of intrinsic control mechanisms regulating cellular proliferation and/or apoptosis. This review will describe the current suppositions of the mechanisms behind the selection and subsequent expansion of Barrett's clones, and focus on some of the principle hallmarks associated with this transition.
Best Pract Res Clin Gastroenterol 2006
PMID:Molecular biology of Barrett's cancer. 1699 63


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