Adenocarcinoma of the rat esophagus in the presence of a proton pump inhibitor: a pilot study

Moore, K.; Barry, Peter J.; Burn, John; Falk, Gregory L.

doi:10.1111/j.1442-2050.2001.00145.x

Cited by 14 publications

(8 citation statements)

References 81 publications

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“…Minimally invasive surgery, with better immediate results as in this study, even good late results in normal children, and better results in NI children, in comparison with open surgery, has been confirmed to be a good therapeutic option. Indeed, side effects of some medical treatments after long utilization are potentially very high [5,19]. This type of managment, certainly in children, has to be honestly compared to that of laparoscopic surgery.…”

Section: Discussionmentioning

confidence: 99%

Long-term outcome of laparoscopic Nissen and Toupet fundoplication in normal and neurologically impaired children

et al. 2003

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Section: Discussionmentioning

confidence: 99%

Long-term outcome of laparoscopic Nissen and Toupet fundoplication in normal and neurologically impaired children

et al. 2003

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“…20,44 The long-term effects of proton pump inhibitor therapy on the cancer risk from Barrett's metaplasia are not yet known, and studies on animal models of reflux have yet to show any reduction in cancer risk following proton pump inhibitor treatment. 36,45 The effect of proton pump inhibitor therapy on surrogate clinical markers of cancer risk has been assessed, including major regression in the total surface area of metaplastic epithelium 18 and prevention of progression to dysplasia. In a small randomized controlled trial, treatment with omeprazole produced a statistically significant regression in Barrett's surface area (average of 9% of the mucosal area), compared with histamine-2 receptor antagonist treatment.…”

Section: Acid Bile and The Drive For Metaplastic Changementioning

confidence: 99%

Review article: management of oesophageal adenocarcinoma — control of acid, bile and inflammation in intervention strategies for Barrett's oesophagus

Jankowski

Anderson

2004

Aliment Pharmacol Ther

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Summary Oesophagitis is associated with Barrett's metaplasia in about 10% of individuals. The UK has one of the highest world‐wide prevalences of Barrett's metaplasia, with 1% of adults having the condition, resulting in an incidence of oesophageal adenocarcinoma two to three times that seen in either Europe or North America. In addition, the conversion rate to cancer in individuals with Barrett's metaplasia in UK surveillance programmes is twice that observed in the USA (0.96% per year vs. 0.4% per year), lending further support to the notion that the UK is a high‐risk region. The evidence base on what can be achieved with medical therapy to reduce the risk of dysplasia or the development of adenocarcinoma needs to be strengthened with data from randomized controlled trials, as existing data have many limitations. Patients with Barrett's metaplasia respond variably to proton pump inhibitor therapy (even high‐dose therapy ‘normalizes’ acid reflux in only 85% of cases), and symptom control is a poor determinant of the adequacy of suppression of acid reflux. Gastro‐oesophageal reflux is implicated in the pathogenesis of Barrett's metaplasia, and ex vivo and in vitro evidence suggests that its attenuation reverses proliferation and biological variables over days, and perhaps the metaplastic histology to a degree over years. The effect of proton pump inhibitor therapy on cancer risk in the long term is essentially unknown. Acid suppressant therapy or anti‐reflux surgery on its own does not result in the complete regression of the metaplastic epithelium. Bile acids, present especially frequently in the refluxate of Barrett's oesophagus patients, are also likely to influence the development and persistence of metaplasia. Barrett's metaplasia is replaced by a squamous epithelium when acid reflux is well controlled and the epithelium is physically destroyed by ablation with argon plasma coagulation or photodynamic therapy. These modalities are invasive and are not likely to be useful in the routine management of patients with Barrett's oesophagus without dysplasia or cancer. Why metaplasia does not fully regress once external initiating stimuli are removed is a mystery. There is some evidence to implicate a variety of molecules, including cyclo‐oxygenase‐2, tumour necrosis factor‐α, β‐catenin nuclear translocation and mitogen‐activated protein kinase signalling, because they are expressed preferentially in metaplastic rather than normal or inflamed squamous oesophageal mucosa. The use of non‐steroidal anti‐inflammatory drugs, including aspirin, is associated with a decreased incidence of oesophageal adenocarcinoma. There is therefore a great need for randomized controlled trials to assess the outcomes of such chemopreventive therapy in patients with Barrett's metaplasia.

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“…Several animal models examined the effect of PPI therapy on DGER. Moore et al (2001) found that the addition of omeprazole did not increase the number of esophageal adenocarcinomas in animals that underwent different forms of surgical reflux to maximize DGER (Netzer et al, 2001). In contrary Nasr et al, 2006) demonstrated that the use of acid suppression therapy in the presence of duodenal refluxate caused increased rates of inflammatory changes, intestinal metaplasia and molecular proliferative activity.…”

Section: Role Of Medication In the Control Of Dgermentioning

confidence: 96%

“…Although none of the rats developed oesophageal cancer, oesophageal mucosal hyperplasia was more pronounced when compared to surgery alone group. Moore et al (2001) performed duodenoesophagostomy on rats to induce duodenal reflux. They treated the study group with a daily intra-peritoneal dose of omeprazole and the control group with normal saline for 6 months.…”

Section: Science Publicationsmentioning

confidence: 99%

“…Patients on long-term omeprazole have decreased acid secretion and an elevated gastric pH. The resultant overgrowth of the duodenal and gastric microflora (Moore et al, 2001;Wetscher et al, 1999a;1999b) may facilitate the deconjugation of bile acids in the stomach. This in turn may increase the concentration of dehydroxylated and more toxic unconjugated bile acids (Menges et al, 2001).…”

Section: Role Of Medication In the Control Of Dgermentioning

confidence: 99%

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Review Article; Duodeno-Gastro-Esophageal Reflux Combined and Isolated

Nasr¹

2013

American Medical Journal

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Barrett's esophagus is the chief risk factor for esophageal adenocarcinoma. Reflux of gastric acid has long been related to the development of esophagitis and Barrett's esophagus, but the role of duodenal contents is controversial. We review the literature on the role of duodenal contents in the development of esophagitis, Barrett's esophagus and adenocarcinoma in addition to the role of acid suppressant therapy in the development or prevention of these changes. A computer-based search of the literature using the terms "Bilirubin, Barrett, Bile Reflux, duodeno-gastric reflux and oesophagus/esophagus" was performed. The role of bile and other constituents of duodenal refluxate were examined. Techniques for identifying nonacid reflux were also reviewed, as were the role of pH, medication and surgery in modulating disease severity. Complicated Barrett's esophagus is associated with increased exposure to gastric and duodenal refluxate. Biological effect of bile acids depends on the conjugation status, the pH of the milieu and the pKa of bile acids. While Proton Pump Inhibitors reduce the levels of DGER, they also produce changes in gastric and lower esophageal pH that activate different bile acids at different pH levels resulting in unexpected injury. Conjugated bile acids are harmful in acidic environment while unconjugated bile acids are harmful at neutral pH environment. An overlap of toxicity among conjugated and unconjugated bile acids occurs between strongly acidic and neutral pH levels. Normalisation of gastric and duodenal refluxate should ideally be the goal of treatment.

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Adenocarcinoma of the rat esophagus in the presence of a proton pump inhibitor: a pilot study

Cited by 14 publications

References 81 publications

Long-term outcome of laparoscopic Nissen and Toupet fundoplication in normal and neurologically impaired children

Long-term outcome of laparoscopic Nissen and Toupet fundoplication in normal and neurologically impaired children

Review article: management of oesophageal adenocarcinoma — control of acid, bile and inflammation in intervention strategies for Barrett's oesophagus

Review Article; Duodeno-Gastro-Esophageal Reflux Combined and Isolated

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