ContextGastroesophageal reflux disease (GERD) is a risk factor for adenocarcinoma
of the esophagus, a rare cancer whose incidence is increasing. Adenocarcinoma
may develop from Barrett esophagus, a metaplastic change of the esophageal
epithelium from squamous to intestinalized columnar mucosa, which is associated
with chronic reflux. Some have recommended that patients with chronic reflux
symptoms undergo upper endoscopy to assess for Barrett esophagus and to screen
for cancer.ObjectivesTo review the evidence linking GERD and Barrett esophagus to esophageal
adenocarcinoma and to examine the utility of upper endoscopy as a screening
tool in adenocarcinoma of the esophagus among individuals with GERD.Data SourcesA MEDLINE search was performed to identify all pertinent English-language
reports about GERD, adenocarcinoma, and Barrett esophagus from 1968 through
2001. Reports were of randomized controlled clinical trials if available,
case-control data if trials were unavailable, and cohort studies if case-control
data were unavailable. Pertinent bibliographies were also reviewed to find
reports not otherwise identified.Study Selection and Data ExtractionStudies were selected by using the search terms gastroesophageal
reflux, adenocarcinoma, and Barrett's esophagus, with subheadings for classification, complications,
drug therapy, economics, epidemiology, mortality, surgery, and prevention
and control. Clinical guidelines for the care of subjects with GERD and Barrett
esophagus were retrieved and abstracted.Data SynthesisCohort studies demonstrate that symptoms of GERD occur monthly in almost
50% of US adults and weekly in almost 20%. Three large case-control studies
demonstrate a positive association between reflux symptoms and risk of adenocarcinoma
of the esophagus, with more prolonged and severe symptoms accentuating this
risk. However, because of the low incidence of adenocarcinoma of the esophagus
and the ubiquity of reflux symptoms, the risk of cancer in any given individual
with reflux symptoms is low. No randomized trial data are available to demonstrate
either decreased cancer incidence or increased life expectancy in subjects
with GERD who undergo screening endoscopy.ConclusionsStrong evidence supports the association of GERD and adenocarcinoma
of the esophagus; however, the risk of cancer in any given individual with
GERD is low. Barrett esophagus appears to be a common precursor lesion to
this cancer. Given the low absolute risk of cancer in those with GERD and
the lack of demonstrated efficacy of endoscopic screening, insufficient evidence
exists to endorse routine endoscopic screening of patients with chronic GERD
symptoms.

https://jamanetwork.com/journals/jama/articlepdf/194842/jsr20006.pdf

Gastroesophageal reflux, Barrett esophagus, and esophageal cancer. Scientific review

The gastric H,K-ATPase is the primary target for the treatment of acid-related diseases. Proton pump inhibitors (PPIs) are weak bases composed of two moieties, a substituted pyridine with a primary pKa of about 4.0, which allows selective accumulation in the secretory canaliculus of the parietal cell, and a benzimidazole with a second pKa of about 1.0. PPIs are acid-activated prodrugs that convert to sulfenic acids or sulfenamides that react covalently with one or more cysteines accessible from the luminal surface of the ATPase. Because of covalent binding, their inhibitory effects last much longer than their plasma half-life. However, the short half-life of the drug in the blood and the requirement for acid activation impair their efficacy in acid suppression, particularly at night. PPIs with longer half-life promise to improve acid suppression. All PPIs give excellent healing of peptic ulcers and produce good results in reflux esophagitis. PPIs combined with antibiotics eradicate Helicobacter pylori.

/pdf/pharmacology-of-proton-pump-inhibitors-xxa28meofq.pdf

Pharmacology of proton pump inhibitors

The physiology and pathophysiology of small bowel motility are reviewed with particular focus on the motility patterns and periods that are detected by intraluminal manometry. Motility patterns are groups of phasic pressure waves resulting from contractions of the circular muscle layer of the small bowel that are organized by the enteric nervous system. Phase III of the migrating motor complex, the hallmark of the fasting motility period, thus reflects enteric neuromuscular function. Response to meal challenge also involves the CNS, reflexes beyond the gut and endocrine responses. Although specific disease diagnosis cannot be made by motility studies of the small bowel, the functional integrity is revealed. The normal occurrence of the essential patterns and periods of motility and the absence of distinctly abnormal patterns evidence preserved function, whereas the opposite indicates clinically significant dysmotility. Certain motility patterns are occasionally seen both in health and disease, and increased prevalence indicates a moderate dysfunction of yet unclear significance. Bacterial overgrowth with Gram-negative bacilli is the consequence of severe small bowel dysmotility, and a diagnosis that can be predicted by a motility study. Testing can be useful in the clinical management of paediatric and adult patients also by predicting the prognosis and response to enteral nutrition and medical therapy. Further studies are, however, needed to take full advantage of motility testing in clinical practise.

The patterns of small bowel motility: physiology and implications in organic disease and functional disorders.

Background Oesophagitis arises when reflux of acid from the stomach into the oesophagus causes mucosal inflammation. It is a common problem and a systematic review on the optimum treatment would be useful. Objectives To assess the effectiveness of proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), prokinetic therapy, sucralfate and placebo in healing oesophagitis or curing reflux symptoms or both. To compare adverse effects with the different treatments. Search strategy We searched MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and the National Research Register until December 2004 and reference lists of articles. We also contacted manufacturers and researchers in the field. Selection criteria Randomised controlled trials assessing the healing of oesophagitis or reflux symptoms or both. Treatment involving PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo for 2 and 12 weeks. Data collection and analysis Two reviews independently assessed trial quality and extracted data. Main results We included 134 trials involving 35,978 oesophagitis participants. Five RCTs evaluated standard dose of PPI versus placebo in 965 participants. There was a statistically significant benefit of taking standard dose PPI therapy compared to placebo in healing of oesophagitis (RR = 0.22; 95% CI 0.15 to 0.31). Ten RCTs reported on the outcome for H2RA versus placebo evaluating 1241 participants. There was statistically significant benefit of taking H2RA compared to placebo in healing of oesophagitis (RR 0.74,95% CI = 0.66 to 0.84). Three RCTs evaluated prokinetic therapy versus placebo in 198 participants. There was no statistically significant benefit of taking prokinetic therapy compared to placebo in healing of oesophagitis (RR 0.71, 95% CI 0.46 to 1.10). Twenty six RCTs reported the outcome for PPI versus H2RA or H2RA plus prokinetics, evaluating 4032 participants. There was statistically significant benefit of taking PPI therapy compared to H2RA or H2RA plus prokinetics in healing of oesophagitis (RR 0.51, 95% CI 0.44 to 0.59). Authors' conclusions PPI therapy is the most effective therapy in oesophagitis but H2RA therapy is also superior to placebo. There is a paucity of evidence on prokinetic therapy but no evidence that it is superior to placebo.

Medical treatments in the short term management of reflux oesophagitis

Occupational engagement is a pre-requisite for continuous income opportunities. Among the changing social circumstances work-related conditions play an increasingly eminent role in psychological and mental well-being. The public discusses the question of a possible association between the demands of modern work life and the increases of psychological, psychosomatic and cardiovascular disorders. Given the socioeconomic implications of psychiatric and psychosomatic suffering in the general population, there is a need to further elucidate the causes of their increasing incidence. From a medical point of view, any organization of work disrupting the phased circadian rhythms for bio-psycho-social processes and functioning of the individual are interesting against the background of clock genes and certain biological functions that are organized in a circadian fashion. The authors review the influence of shift work as a form of systematic desynchronization of inner clock systems on the endocrine, the physical, and the mental level. The significance of the findings in the field is discussed along with future directions of conclusive research.

The effects of shift work on physical and mental health

This paper describes a new technique for ambulatory long-term monitoring of small-bowel motility. Intraluminal pressure was measured with a silicon catheter with two strain-gauge transducers spaced...

Digital ambulatory monitoring of small-bowel motility.

Background: Development of electrogastrography, the recording of gastric electric rhythm from cutaneous electrodes, for clinical purposes has been hampered by methodologic problems and the lack of an ambulatory technique. We have evaluated a newly developed system for ambulatory electrogastrography. Methods: 24-Hour recordings were obtained from 30 healthy volunteers. We used digital filtering, a Hamming window, and spectral analysis to determine the dominant frequency of successive 256-sec segments of data. Results: Low-frequency noise disturbed the primary signal. After secondary filtering a stable normogastric (2-4 cpm) rhythm was present during a median of 49% (range, 34-79%) of the recording time. The mean frequency of gastric electric activity varied from 2.92 ± 0.15 cpm (mean ± SD) at mid-day to 2.72 ± 0.13 cpm in the late night. Conclusions: Ambulatory recording of electrogastrography needs technical improvement. The electrogastrogram shows a circadian variation in frequency.

24-Hour Ambulatory Electrogastrography in Healthy Volunteers

Background: Our aim was to evaluate which specific factors are of importance for the gastroesophageal reflux seen in presumably healthy subjects. Methods: We investigated 57 healthy, asymptomatic volunteers with computer-aided medical history interrogation, endoscopy, biopsy specimens from the distal esophagus, manometry, and 24-h ambulatory pH-monitoring. Results: Eight subjects (14%) claimed intermittent reflux symptoms at the computer interview, but they did not have more acid reflux at pH-monitoring than asymptomatic volunteers. Thirteen subjects (23%) had abnormalities at endoscopy, 3 of whom had an erosion in the distal esophagus, and 12 had hiatus hernia. Subjects with hiatus hernia had increased acid reflux at 24-h pH-monitoring compared with those without hernia. If subjects with hernia were excluded, the degree of acid reflux was similar in all age groups. Men had more acid reflux than women, and these differences persisted if subjects with hernia were excluded. There was no correlation of histo...

Gastroesophageal reflux in healthy subjects. Significance of endoscopic findings, histology, age, and sex.

Background: Lansoprazole (LAN) and omeprazole (OME) heal esophagitis effectively and to similar extents, but LAN has a faster effect on the relief of symptoms of gastroesophageal reflux. However, no strict comparison of the two proton pump inhibitors' effect on acid reflux and gastric acidity has been published. The aim of this study was to compare the effects of LAN and OME on gastroesophageal reflux with simultaneous measurements of gastric acidity in patients with established gastroesophageal reflux disease (GERD) and esophagitis. Methods: Fourteen patients with endoscopically verified erosive esophagitis and with a pretreatment esophageal 24-h pH measurement showing acid reflux to the esophagus participated in the study. This was a double-blind, randomized study with crossover design. Before (day 0) and on the last day (day 5) of each treatment period with encapsulated 30 mg LAN or 20 mg OME daily, 24-h intraesophageal and intragastric acidity were measured with antimony electrodes connected to an amb...

Comparison of the effect of lansoprazole and omeprazole on intragastric acidity and gastroesophageal reflux in patients with gastroesophageal reflux disease.

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Digital ambulatory monitoring of small-bowel motility.

24-Hour Ambulatory Electrogastrography in Healthy Volunteers

Gastroesophageal reflux in healthy subjects. Significance of endoscopic findings, histology, age, and sex.

Comparison of the effect of lansoprazole and omeprazole on intragastric acidity and gastroesophageal reflux in patients with gastroesophageal reflux disease.