Gastro-oesophageal reflux disease

doi:10.1016/S0140-6736(06)68932-0

The Lancet

Volume 367, Issue 9528, 24–30 June 2006, Pages 2086-2100

https://doi.org/10.1016/S0140-6736(06)68932-0 Get rights and content

Summary

Gastro-oesophageal reflux disease refers to reflux of gastric contents into the oesophagus leading to oesophagitis, reflux symptoms sufficient to impair quality of life, or long-term complications. Transient relaxation of the lower oesophageal sphincter is believed to be the primary mechanism of the disease although the underlying cause remains uncertain. Obesity and smoking are weakly associated with the disease and genetic factors might be important. A negative association with Helicobacter pylori exists, but eradication of H pylori does not seem to cause reflux disease. Diagnosis is imprecise as there is no gold standard. Reflux symptoms are helpful in diagnosis but they lack sensitivity. Ambulatory oesophageal pH monitoring also seems to be insensitive despite high specificity. Empirical acid suppression with a proton-pump inhibitor (PPI) has reasonable sensitivity but poor specificity. Some evidence suggests that once patients develop the disease, severity is determined early and patients seem to continue with that phenotype long term. Unfortunately, most patients do not respond to life-style advice and require further therapy. H₂ receptor antagonists and PPIs are better than placebo in oesophagitis, with a number needed to treat of five and two, respectively. In non-erosive reflux disease, acid suppression is better than placebo but the response rate is lower. Most patients need long-term treatment because the disease usually relapses. The role of endoscopic therapy is uncertain. Anti-reflux surgery is probably as effective as PPI therapy although there is a low operative mortality and morbidity.

Introduction

Gastro-oesophageal reflux disease is a common problem and is expensive to manage in both primary and secondary care settings. The annual direct cost for managing the disease is estimated to be more than $9 billion dollars in the USA.¹ There have been major advances in the diagnosis, pathophysiology, and treatment of this disease, which we will review here.

Section snippets

Definitions

There is no gold standard test for objectively diagnosing gastro-oesophageal reflux disease, and definitions have therefore relied on a combination of disease characteristics. For example, an international working group² defined the disease as the reflux of gastric contents into the oesophagus leading to oesophagitis, reflux symptoms sufficient to impair quality of life, or risk of long-term complications. This definition builds on previous ones3, 4 and emphasises that gastro-oesophageal reflux

Epidemiology

There have been a series of systematic reviews that have improved understanding of the epidemiology of the disease.8, 9, 10, 11

Pathophysiology

The primary underlying mechanism could be impaired function of the lower oesophageal sphincter—a segment of smooth muscle in the distal oesophagus that tonically contracts so that the pressure in this area is at least 15 mm Hg above intragastric pressure.⁴⁹ This mechanism acts as a physiological barrier to prevent gastric contents from refluxing into the oesophagus. The sphincter relaxes in response to oesophageal peristalsis to allow the passage of food, liquid, or saliva into the stomach.

Diagnosis

The lack of a gold standard has hampered the assessment of the accuracy of various approaches to the diagnosis of gastro-oesophageal reflux disease. The absence of a reference standard can be overcome by use of techniques such as latent class analysis and Bayesian analysis, but as yet these methods have not been used in the assessment of the disease.⁶³ The accuracy and use of the different approaches to diagnose the disease are therefore uncertain. The tools available for diagnosis are

Complications and extra-oesophageal manifestations

There is a paucity of data on the long-term outcome of patients with different severities of reflux disease. Patients with severe symptoms over a long duration might intuitively be expected to be at higher risk of more severe reflux disease. Severity and duration of symptoms, however, seem to have a poor correlation with the presence or severity of oesophagitis.⁹¹ A US veteran database study of more than 29 500 patients with uncomplicated erosive oesophagitis reported no patients developing

Treatment

Lifestyle advice and antacid therapy is advocated as first-line treatment for the disease. Lifestyle factors are only weakly associated with reflux symptoms, so it is unlikely that these will have a major effect on the disease. Nevertheless, advice such as stop smoking, reduce alcohol intake, and weight loss in obese patients is likely to have wider benefits, even if the effect on reflux symptoms is small. There is some evidence from a randomised trial¹⁰⁵ that antacid therapy has a small effect

Management

There have been several guidelines3, 4, 185, 186, 187, 188 published on the management of the disease (table 2). There is a consensus that PPIs are the most effective therapy and should be continued long term at the lowest dose that controls symptoms. All agree that endoscopy has a role in the investigation of the disease, but the threshold at which endoscopy is recommended varies. The guidelines recommend surgery for selected cases. We have constructed a management strategy based on common

Search strategy and selection criteria

We did a MEDLINE search of articles published between 1966 and August, 2005, using the terms “oesophagitis”, “gastro-oesophageal reflux”, “peptic oesophagitis”. All terms were merged using the set operator “OR” and the search was limited to “human” and “English language” studies.

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Of 122 screened, 21 NERD and 21 control subjects were identified (mean age, 49.5 ± 14.6 years; 62% men; and 85% white). The combination of IPCL tortuosity, RVP, and microerosions (62% vs 19%, P < .05) had a high specificity (86%) and moderate sensitivity (60%) for NERD with an area under the curve of .74. In 10 NERD patients treated with PPIs, resolution of microerosions was most significant (P = .047) compared with placebo (n = 11). RVP resolved in all NERD patients after therapy (P = .02) and correlated with acid exposure time (P = .004). Papillary length (P = .02) and basal cell thickness (P = .02) significantly correlated with a combination of IPCL tortuosity, RVP, and microerosions.
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SeminarGastro-oesophageal reflux disease

Summary

Introduction

Section snippets

Definitions

Epidemiology

Pathophysiology

Diagnosis

Complications and extra-oesophageal manifestations

Treatment

Management

Search strategy and selection criteria

Gastroenterology

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Am J Med Sci

Gastroenterology

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