Symptom recognition and assessment

The diagnosis of GORD is mostly based on symptom assessment. The most characteristic and common symptom is heartburn. However, it is important to use descriptive language such as ‘a burning feeling rising up from the stomach or lower chest towards the neck’, as the term ‘heartburn’ is widely interpreted and has variable meaning in different cultures. Regurgitation is also common. Excessive belching, odynophagia and waterbrash (sudden filling of the mouth with saliva) also occur in GORD. Periodic dysphagia is not infrequent, but new onset, frequent or progressive dysphagia is an indication for prompt endoscopy to exclude mechanical obstruction due to peptic strictures or malignancy. Overt bleeding occurs occasionally but is rarely severe. Occult iron deficiency may result from oesophagitis or from Cameron lesions (linear erosions caused by mechanical trauma due to the effect of the diaphragm on a hiatal hernia sac). However, iron deficiency should not be ascribed to oesophagitis or hiatal hernia without considering colonic causes for blood loss.

Accurate recognition of heartburn has reasonable sensitivity for the diagnosis of reflux. Assessment of the duration, frequency and severity of this and other symptoms and of the impact of symptoms on quality of life will determine if GORD is present and allow grading of the severity of the condition, which in turn guides the intensity of therapy.

Atypical symptoms include chest pain, which may mimic cardiac pain, and symptoms associated with extra-oesophageal manifestations of GORD including cough, sore throat, hoarseness and wheeze. GORD should be considered in patients who present with no other apparent cause for these symptoms although most patients with reflux-induced extra-oesophageal symptoms will also have typical GORD symptoms.

Symptoms of GORD may be similar to those of other upper gut disorders, especially peptic ulcer disease and functional dyspepsia. About two-thirds of patients with reflux symptoms will also complain of upper abdominal pain or discomfort (dyspepsia). In some GORD patients epigastric pain may be the major symptom of GORD and in these cases it is difficult to distinguish GORD from other conditions.

About 40% of patients with irritable bowel syndrome also complain of reflux symptoms. Such an overlap suggests both conditions may be part of the spectrum of a broader gastrointestinal disorder representing variations in the presentation of an irritable gut.

GORD symptom severity is not a reliable guide to the presence or severity of oesophagitis. In some patients, particularly the elderly or intellectually disabled patients, severe oesophagitis may be present with only mild symptoms. The presence of dysphagia, odynophagia, nocturnal choking, haematemesis or weight loss should alert the clinician to the possibility of severe or complicated GORD, or to an alternative serious diagnosis.

The therapeutic trial as a diagnostic test

A symptom-based diagnosis of GORD is often followed by a therapeutic trial of a standard dose of a proton pump inhibitor (PPI), and a response to this is inferred to support the diagnosis of GORD. When there is uncertainty about the diagnosis, particularly when there are atypical or extra-oesophageal symptoms, twice-daily PPI dosing is used. The optimal duration for this ‘PPI test’ is not known. Typical symptoms often respond within 2 weeks but, for extra-oesophageal symptoms, up to 8 weeks of treatment may be required. The PPI test is often assumed to have major diagnostic value for GORD but meta-analysis reveals that the sensitivity and specificity of this is moderate only, although it may be comparable to that of oesophageal pH monitoring.

The role of endoscopy

It is inappropriate to investigate every patient with suspected GORD. Patients who have mild, typical reflux symptoms and no alarm symptoms may be given a trial of therapy without investigation.

Endoscopy is warranted if the diagnosis is unclear, because symptoms are either non-specific or atypical for GORD or are ‘mixed’ with upper gut symptoms, such as epigastric pain (Table 3.1). Endoscopy should also be undertaken for symptoms that persist or are refractory to treatment, when complications are suspected or there are alarm symptoms present (weight loss, dysphagia, odynophagia, bleeding or anaemia).

TABLE 3.1 Endoscopy recommendations

Endoscopy is specific but not sensitive for the diagnosis of GORD as most patients have non-erosive GORD. However, it has an important role in the evaluation of GORD in selected patients. It allows the exclusion of alternative diagnoses, an assessment of the severity of oesophagitis (graded A–D by the LA classification), the diagnosis of complications and may allay physician and patient anxiety.

Barium swallow has a minor role in investigating GORD, except in some cases where it may be useful to plan management in patients with persistent dysphagia when a stricture is suspected or for the assessment of a large hiatal hernia.

Ancillary tests

Medical therapy

PPIs are the most effective therapy for GORD, providing rapid and reliable symptom resolution and healing of oesophagitis in most patients (80% after 8 weeks). Management involves a first phase of diagnosis, assessment of severity and initial trial of once-daily PPI therapy, usually given before breakfast, for 4–8 weeks (Figure 3.3). Patients with prominent evening or nocturnal symptoms may be dosed before the evening meal. A positive initial response to PPI therapy supports the clinical diagnosis, relieves symptoms, reassures the patient and heals oesophagitis if present. While the majority of patients with GORD will achieve good control of symptoms, a substantial minority will not. These patients are more likely to have non-erosive GORD with less acid reflux demonstrable and are less responsive to acid suppression.

FIGURE 3.3 Management pathways for GORD.

GORD = gastro-oesophageal reflux disease; PPI = proton pump inhibitor.

The second or maintenance phase involves tailoring an individualised long-term plan using the lowest dose and frequency of drug possible. The aim is to control symptoms and minimise relapses, reduce the risk of complications of the disease or of therapy and to minimise costs. Patients with longstanding, severe symptoms or a higher grade of oesophagitis need continuous PPI therapy, as relapse is inevitable if treatment is withdrawn. A few patients need twice-daily dosing. Milder disease is treated with less intense therapy. A trial of treatment cessation is warranted in patients with short-term symptoms as not all patients relapse. An attempt can be made to ‘step down’ to a lower PPI dose or to an H₂-receptor antagonist (H₂-RA). Intermittent, self-directed (‘on demand’) therapy is effective for some patients with less frequent symptoms. Patient-directed use of antacids, antacid/alginate combinations or ‘over the counter’ H₂-RAs may be helpful for the relief of mild and occasional reflux symptoms but are adjunctive treatment only for significant GORD. Prokinetic agents have little role in management.

PPIs are safe drugs but minor adverse effects may include headache, nausea and diarrhoea. There is a slightly increased risk of community acquired pneumonia, and bacterial gastroenteritis. Interstitial nephritis occurs rarely with PPI use. Initial concerns about potential risk of long-term acid suppression have not been realised after 20 years of PPI usage, but ongoing surveillance is required. PPIs have a very low rate of clinically important drug interactions.

Lifestyle modification

Weight loss in obese patients improves symptoms of GORD and should be advised. Lifestyle modification including dietary fat reduction, avoidance of foods that precipitate symptoms and smoking cessation are adjunctive measures that may be helpful.

Surgical therapy of GORD

Laparoscopic fundoplication may provide effective long-term control of reflux symptoms. Results are operator dependent and, as such, vary considerably. Patient selection is crucial to outcome. Patients who respond well to PPIs usually obtain good symptom control with surgery and in these patients the decision is one of informed choice. Those with atypical symptoms, who are endoscopy negative and unresponsive to acid suppression fare poorly with fundoplication. Surgery should be considered in the few patients with medically refractory GORD and in patients with problematical ‘volume reflux’ or symptoms derived from large and particularly para-oesophageal hernia. Fundoplication does not cause regression of Barrett’s epithelium or reduce cancer risk. There is a risk of death (0.2%) and serious morbidity from fundoplication. Although the absolute risk is relatively small, it exceeds that for PPIs. Perioperative complications include surgical mishap and the need for conversion to open fundoplication. Common adverse effects are inadequate symptom control (re-operation rate 3%–6%) and a need for ongoing antisecretory medication (20%–60%) which increases over time. Troublesome new symptoms include dysphagia, ‘gas bloat’ syndrome and diarrhoea, and these may be difficult to manage.

Endoscopic antireflux therapy

Endoscopic procedures have been developed as alternatives to laparoscopic fundoplication. Adequate comparative short-and long-term efficacy data are lacking and safety issues are unresolved. Although these techniques are being used, at present such techniques should be considered experimental and their use confined to clinical trials in major centres.

GORD, PPIs and Helicobacter pylori

Helicobacter pylori infection is present frequently in patients with GORD as both conditions are common. However, H. pylori does not cause GORD. Similarly, infection does not reduce the risk of developing GORD, except in the minority of patients in whom infection causes marked gastric mucosal atrophy with reduced acid secretion. These patients are somewhat less likely to develop severe oesophagitis and Barrett’s mucosa but are at greatly increased risk of gastric adenocarcinoma and eradication therapy is advisable. Reflux symptoms are not better controlled with PPIs in patients who are H. pylori-positive and eradication of H. pylori does not significantly increase the risk of GORD developing.

In H. pylori infected patients, PPI therapy causes a worsening of the histological grade of gastritis and an accelerated risk of gastric mucosal atrophy and intestinal metaplasia. This is not seen when PPIs are used in uninfected patients or in those in whom H. pylori has been eradicated prior to long-term PPI use. As these changes are risk factors for gastric adenocarcinoma, eradication of H. pylori is recommended prior to long term PPI therapy for GORD, particularly in younger patients.

PPIs affect the accuracy of biopsies (urease test and histology) and breath tests for H. pylori so testing is best done prior to PPI therapy or after cessation of PPIs for at least one week and preferably two.

Barrett’s oesophagus

Definitions of Barrett’s oesophagus vary, but the core component is the presence of metaplastic columnar epithelium from the gastro-oesophageal junction and extending proximally. Specialised intestinal metaplasia (SIM) is often identified in this metaplastic epithelium and it is the presence of SIM that confers the risk of progression to dysplasia and adenocarcinoma. For this reason the presence of oesophageal SIM identified by histological examination of biopsy specimens is considered a prerequisite for the diagnosis of Barrett’s oesophagus by some, whereas others prefer to describe Barrett’s oesophagus on endoscopic appearances and then specify the presence or absence of SIM after biopsy results are available. The endoscopic description of Barrett’s oesophagus should include a standardised measure of extent.

About 4%–8% of Caucasian patients with GORD who undergo endoscopy will have Barrett’s oesophagus. Caucasian males aged over 50 years have the highest risk for the development of Barrett’s oesophagus and progression to adenocarcinoma. Obesity and smoking are added risk factors.

The majority of people with a Barrett’s oesophagus remain undiagnosed and unaware of the condition. The frequency and severity of heartburn are not useful for the prediction of the presence of Barrett’s oesophagus. There is no evidence that acid control by PPIs or surgery reverses the condition. Whether PPI therapy reduces the risk of progression to dysplasia remains to be confirmed.

There is no evidence that general population screening for Barrett’s oesophagus will affect mortality from oesophageal adenocarcinoma. Furthermore, there is no convincing evidence that screening all patients with GORD for Barrett’s oesophagus by endoscopy would be of benefit. Targeted screening of individuals at higher risk of developing the condition has been proposed. When patients who have endoscopy to evaluate GORD are found to have Barrett’s oesophagus, ongoing endoscopic surveillance is often offered, although there is no unequivocal evidence for a clinical or health economic benefit from such a strategy. When Barrett’s oesophagus is found, multiple biopsies should be obtained in four quadrants at 2 cm intervals along the Barrett’s mucosa to determine if SIM is present and to search for dysplasia or cancer. The highest yield for this occurs at the initial diagnosis of Barrett’s oesophagus and not during subsequent surveillance. The risk of progression to cancer appears greater for those with long-segment Barrett’s oesophagus (>3 cm) and has been estimated to be about 0.5% annually. Surveying patients with short-segment Barrett’s oesophagus (<3 cm) or SIM occurring just at or above the gastro-oesophageal junction is controversial as the cancer risk is lower.

When Barrett’s oesophagus is found or suspected in the presence of oesophagitis, epithelial atypia or dysplasia may be misdiagnosed. In this case the examination needs to be repeated after mucosal healing with PPIs. Surveillance of Barrett’s oesophagus after initial diagnosis aims to identify patients who progress to high-grade dysplasia or early adenocarcinoma so that appropriate intervention can be provided to improve survival. The optimal surveillance interval is not defined. Generally, 2–3-yearly biopsies are recommended.

As the likelihood of Barrett’s oesophagus increases with advancing age, many patients with Barrett’s oesophagus have substantial comorbidities and increased risk for mortality from other causes. Moreover, oesophagectomy for high-grade dysplasia or cancer has significant risks in older patients. For these reasons, endoscopic techniques for treating Barrett’s oesophagus and dysplasia are being trialled in specialised centres. Such techniques include endoscopic mucosal resection or ablative methods such as photodynamic therapy, laser therapy, multipolar electrocoagulation, argon plasma coagulation, radiofrequency ablation and cryotherapy. Whether ablation therapy eliminates or significantly reduces the risk of cancer or reduces the need for ongoing surveillance is not known and it is yet to be determined whether the risks associated with these therapies are less than the risk of Barrett’s oesophagus progressing to cancer.

When low-grade dysplasia is found, repeat endoscopy with biopsies should be done within 6 months, with the patient on PPIs, to determine if high-grade dysplasia has been missed. If low-grade dysplasia persists, re-surveillance at 6 months and then annually is recommended.

When high-grade dysplasia is found, it is mandatory to have the pathology reviewed by another pathologist and, if there is doubt, to repeat the biopsies. About one-third of patients with high-grade dysplasia have an underlying cancer and a variable number (15%–60%) will progress to cancer within 4 years especially when high-grade dysplasia is multifocal. When high-grade dysplasia is confirmed, consideration for oesophagectomy is an option in patients fit for surgery. An alternative is intensive surveillance (every 3 months) until intramucosal cancer is detected, then surgery (as not all dysplasia will progress to cancer), but such a strategy is problematical. If the patient declines or is not fit for surgery, endoscopic techniques are an option.