Clinical Review - Gastro-oesophageal reflux disease

By Dr Kathryn Oakland, foundation doctor, North East Thames and Mr Joseph Dawson, specialist registrar, North East Thames Section

Barrett's oesophagus, a possible complication of reflux symptoms (Photograph: SPL)
Barrett's oesophagus, a possible complication of reflux symptoms (Photograph: SPL)

Section 1 Epidemiology and aetiology.
Gastro-oesophageal reflux is the involuntary passage of gastric contents from the stomach into the oesophagus, and in small volumes is a normal physiological process. When associated with pain it is called gastro-oesophageal reflux disease (GORD).1

GORD is one of the most common problems in medical practice,2 and it is thought that up to 25 per cent of the population suffer with symptoms of GORD on a regular basis.1 Drug treatment of GORD accounts for the largest single pharmacological expenditure in the NHS.2

Oesophageal mucosa changes that occur as a result of severe GORD may also be responsible for the rising incidence of oesophageal adenocarcinoma.2

Normal oesophageal transport occurs by peristalsis from the upper oesophageal sphincter in the cervical oesophagus to the lower oesophageal sphincter (LOS). Reflux of stomach contents is prevented by the LOS, which contains a high-pressure zone in the distal 1-4cm that relaxes to allow swallowing.

In addition, external mechanical factors contribute to its function, including a 'flap valve' mechanism created by the oblique angle of entry of the oesophagus to the cardia of the stomach (angle of His), and the phreno-oesophageal ligament that prevents herniation of the abdominal oesophagus through the diaphragm.

Pathophysiology of GORD
Failure of the LOS and its supportive mechanisms can result in reflux of stomach contents into the oesophagus. A small amount of acid reflux may cause no symptoms, but significant reflux can lead to the symptoms of GORD. The pathophysiology of GORD is not completely understood but is almost certainly multifactorial (see table). GORD is also associated with transient lower oesophageal sphincter relaxations (TLOSR), which are not a result of the normal swallowing mechanism.

Risk factors
Studies have demonstrated an increased prevalence of GORD in current and ex-smokers.3 Although dietary factors such as alcohol, coffee, chocolate and fat have also been implicated, there is less definitive evidence implicating them as trigger factors.4

TLOSR and the mechanical causes of GORD lead to abnormal exposure of the distal oesophageal mucosa to the acidic contents of the stomach, which can eventually lead to reflux oesophagitis, stricturing, Barrett's oesophagus and perhaps adenocarcinoma.

There is currently no evidence to associate Helicobacter pylori and GORD.

Mechanisms implicated in development of GORD
Oesophageal Reduced ability to clear secretions
Reduced mucosal protective factors
Poor motility
LOS Decreased pressure
Decreased total length
Decreased intra-abdominal length
Stomach Loss of angle of His ('flap valve' mechanism)
Sliding hiatus hernia
Excess acid production
Delayed emptying
Duodenal Increased duodenogastric reflux
Other Reduced saliva production
Increased proinflammatory factors in reflux fluid

Section 2: Making the diagnosis
Typical symptoms of GORD include heartburn and burning retrosternal or epigastric pain, which may be confused with angina pectoris. This may be associated with regurgitation of stomach contents, waterbrash, dysphagia and odynophagia.5

Less typical symptoms include back pain, chronic nausea, halitosis, metallic taste, nocturnal wheeze, sore throat, poor dentition and hoarse voice.5 Symptoms may be positional and worse at night. These symptoms are also found in other diseases comprising important differential diagnoses (see table).

Investigations
There are a range of complementary modalities available for the investigation of GORD. Endoscopic examination in the form of an oesophagogastroduodenoscopy is the most common initial investigation in the assessment of GORD. It allows direct visualisation and biopsies or brush cytology if required.

In addition to identifying other pathologies, the severity of reflux oesophagitis can be graded by the extent of erosions and the presence of complications such as stricturing. However, only 30 per cent of GORD patients have evidence of inflammation at endoscopy, and this number is reduced if they have been treated with PPIs.

Barium swallow may show strictures, tumours, diverticulae or an irregular distal mucosa in severe reflux oesophagitis.

When combined with video fluoroscopy, contrast studies can give dynamic visualisation of the oesophagus, leading to information regarding function and LOS competence.5

pH measurement
Oesophageal pH measurement is considered the gold standard investigation to objectively quantify acid reflux.

However, it is not required in the majority of patients with GORD if there is a typical history, evidence of oesophagitis at endoscopy and improvement in symptoms with the use of a PPI.

Oesophageal pH monitoring is usually used in combination with manometry for patients in which diagnosis is uncertain, or when considering surgery.

It is a 24-hour, ambulatory investigation involving the insertion of a pH probe into the distal oesophagus, which records acid reflux episodes as they occur.

The patient presses a button when they suffer symptoms to determine any correlation between the symptoms and reflux episodes.

The results are given as the total number of reflux episodes lasting more than five minutes, and the total acid reflux time as function of the total recording time. At 5cm above a LOS, a normal individual will have a pH<4 for less than 4 per cent of a 24-hour period.

Patients with abnormal pH studies can be classified by the DeMeester score that combines the number and length of reflux episodes. It must be remembered that pH studies can be normal in symptomatic patients and in up to 25 per cent of patients with endoscopic oesophagitis.2

Although pH monitoring can diagnose and quantify GORD, it does not offer information regarding the underlying cause, which is usually due to abnormalities around the LOS.

Oesophageal manometry may indicate the cause of GORD by determining the length, position and pressure of the LOS, in addition to peristalsis down the oesophagus and motility in the distal oesophagus. A LOS pressure of <4mmHg is abnormal and may be an indication for surgery.

In addition, manometry identifies achalasia, which is an absolute contraindication to isolated antireflux surgery.

Differential diagnosis

Oesophagus
 
Carcinoma
Benign stricture
Achalasia
Scleroderma
Stomach Peptic ulcer
Hiatus hernia

 

Section 3: Managing the condition
Conservative measures include avoidance of precipitating factors such as spicy foods, alcohol or coffee, sleeping with a raised head of bed, and changing meal times to avoid sleeping with a full stomach. In addition, general lifestyle measures include weight loss, smoking cessation and avoidance of tight abdominal clothing.

Unfortunately these measures alone are rarely adequate to fully control symptoms.6

Medical management
The mainstay of medical treatment of GORD relies on PPIs.

Although other agents are available, they tend to be less effective. Antacids neutralise the pH of the stomach contents and alginates coat the mucosa of the oesophagus to form a protective barrier; however, their effects are short-lived.5

Prokinetic agents act by acc-elerating gastric and oesophageal emptying but again, their use is limited.

H2-receptor antagonists (such as cimetidine and ranitidine) reduce stomach acid production and revolutionised the treatment of duodenal ulcer disease in the 1970s. However, their effect on GORD is less dramatic; they are required long-term, and they tend to have a diminishing effect.6

PPIs (such as omeprazole and lansoprazole) are more effective in symptom relief and the healing of oesophagitis than H2-receptor antagonists6 and have therefore superseded them. A dose of PPI can treat oesophagitis, but as symptoms rapidly return if they are stopped, a lower maintenance dose is often required in the longer term.

PPIs are not as effective in more severe oesophagitis and in these cases, a second generation PPI (for example, esomeprazole) may be used, which is longer lasting and has greater anti-secretory activity.

Surgery
Surgery aims to correct the underlying cause of GORD by reconstructing an antireflux valve at the gastro-oesphageal junction.6 In doing so, it can achieve not only control of gastric reflux, but also duodenal biliary reflux, one cause of PPI therapy failure.6

Laparoscopic nissen fundoplication is the mainstay of the techniques used, consisting of a 360 degs wrap of the stomach fundus around the distal oesophagus. Laparoscopic fundoplication is associated with good long-term results and low complication rates; as a result, open surgery is only reserved for some revision procedures.

One major side-effect of fundoplication is dysphagia, and this has resulted in the development of partial wraps ranging from 120 degs to 300 degs.6 Studies have shown that symptom control is equivalent to a full wrap and that partial wraps are associated with faster recovery of swallowing.

After surgery, most surgeons advise patients to follow a liquid or semi-solid diet for the first few weeks until swallowing returns to normal. Other complications of fundoplication include persistent reflux, gas bloat syndrome and loss of ability to belch or vomit.

A meta-analysis comparing medical management to laparascopic fundoplication showed that surgery was associated with significantly lower rates of regurgitation and heartburn at one year, but increased rates of severe dysphagia.7 Long-term results are awaited.

Referral
Antireflux surgery may be considered in patients who do not respond to medical therapy, defined as a standard dose PPI for three months.6 Younger patients who do not want to take lifelong drugs may also be considered for surgery.

A final group is patients who develop complications such as ulceration, stricturing, Barrett's oesophagus and respiratory problems despite medical therapy.

Section 4: Complications and side-effects
Patients who continue to have reflux symptoms despite medical or surgical management are at risk of developing complications. Oesophageal strictures present with dysphagia and treatment involves endoscopic dilatation followed by long-term PPI or antireflux surgery.

Barrett's oesophagus is the metaplastic replacement of normal squamous epithelium with columnar epithelium, and has malignant potential. Diagnosis is made via endoscopy and histology. Treatment involves lifelong acid suppression and regular surveillance endoscopy.

Long-term PPI use
As symptoms often recur following cessation of PPIs, patients may require lifelong PPIs. Although chronic use is safe, long-term PPI use has been associated with atrophic gastritis with interstitial metaplasia in patients with H pylori and parietal cell hyperplasia.6 In addition, PPI use is associated with Clostridium difficile- associated diarrhoea.8

Side-effects of surgery
Antireflux surgery is effective in 85-90 per cent of patients.5 The most common complications are persistent symptoms of acid reflux (5-8 per cent), dysphagia (<5 per cent), gas bloat syndrome and the inability to belch or vomit.

Dysphagia in the initial postoperative period usually only requires reassurance as oesophageal function returns to normal. Those patients suffering with persistent dysphagia after three months require investigation with a barium swallow to exclude excessive hiatal tightness, fibrosis or malposition of the wrap.

If symptoms persist, revision of the wrap may be required, consisting of conversion to a partial wrap, or complete disassembly of the fundoplication.

Gas bloat syndrome is the trapping of gas within the fundus of the stomach and may cause epigastric pain, abdominal bloating and increased flatus per rectum. The patient may complain of feeling the need to belch without being able to.

Such symptoms after previously good control postsurgery may indicate wrap disruption. This may be preceded by vomiting or belching. In some cases, this represents a loosening of the wrap and symptoms may settle down after a few weeks.

Investigation again involves barium swallow and if normal, possibly pH studies. If there is wrap disruption, revision surgery may be required.

References
1. Beckingham IJ, Graetz K. Benign surgical diseases of the gastro-oesophageal junction. Surgery (Oxford) 2008; 26: 435-8.

2. Barnham CP, Alderson D. Pathophysiology and investigation of gastro-oesophageal reflux disease. In: Griffin MS, Raines SA (editors). Oesophagogastric surgery. A companion to specialist surgical practice. London, Elsevier Saunders, 2006.

3. Ruigomez A, Garcia Rodriguez LA, Wallander MA et al. Natural history of gastro-oesophageal reflux disease diagnosed in general practice. Aliment Pharmacol Ther 2004; 20: 751-60.

4. Dent J, El-Serag HB, Wallander MA et al.

Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2005; 54: 710-7.

5. Ackroyd R. Reflux oesophagitis. Surgery (Oxford) 2003; 21: 9-13.

6. Watson DI, Jamieson GG. Treatment of gastro-oesophageal reflux disease. In: Griffin MS, Raines SA (editors). Oesophagogastric surgery. A companion to specialist surgical practice. London, Elsevier Saunders, 2006.

7. Wileman SM, McCann S, Grant AM et al. Medical versus surgical management for gastro-oesophageal reflux disease (GORD) in adults. Cochrane Database Syst Rev 2010, Issue 3. Art No: CD003243. DOI: 10.1002/14651858.CD003243.pub2.

8. Cunningham R, Dial S. Is over-use of proton pump inhibitors fuelling the current epidemic of Clostridium difficile-associated diarrhoea? J Hosp Infect 2008 ; 70: 1-6.

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