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Advances in gastroenterology

Important advances in screening, diagnosis and therapy should transform care, argues Professor Paul Moayyedi

Reviewing recent advances in gastroenterology is fraught with problems. The brave new world we predict is unlikely to be entirely accurate. Some new technology now emerging may become routine but some will end up historical curiosities. What follows is my personal view of the most important advances in screening, diagnosis and therapy most likely to change practice over the next few years.

Screening

Colorectal cancer is a major cause of mortality in the UK causing almost 16,000 deaths each year. The Government will soon announce whether it is going to recommend a screening programme to detect colorectal neoplasia at a more treatable stage.

Three methods have been proposed: faecal occult-blood testing, flexible sigmoidoscopy and colonoscopy.

A systematic review identified three randomised controlled trials suggesting faecal occult-blood testing could reduce colorectal cancer mortality by up to 20 per cent1. Flexible sigmoidoscopy could have a greater impact on colorectal cancer mortality and preliminary results from the UK look promising. Fifty-year old subjects who agreed to a screening flexible sigmoidoscopy were randomised to screening or no intervention: 40,674 patients underwent flexible sigmoidoscopy with 1.2 per cent and 0.3 per cent having high-risk polyps and colorectal cancer respectively2; 62 per cent of the colorectal cancers were detected early and were potentially curable ­ higher than seen in patients referred to secondary care with lower gastrointestinal symptoms.

This trial has not shown a reduction in colorectal cancer mortality but initial results are encouraging and we await follow-up data with anticipation. About a third of colorectal cancers are beyond the reach of the flexible sigmoidoscope and this has prompted researchers in the US to promote colonoscopy screening programmes3.

It is likely the UK Government will advocate faecal occult blood screening as this has the most evidence for efficacy and is the least expensive to implement. Screening colonoscopy is the strategy likely to detect the most early cancers but at a very high cost and with increased risk of perforation.

Screening flexible sigmoidoscopy may be an acceptable compromise once trial data is complete, although arguments about how often patients should be screened and whether this approach is

cost-effective will continue for many years.

Diagnosis

In 2000 Nature published a paper on a videotelemetry capsule small enough to be swallowed4 (see below). The paper's significance was such that the last time Nature published a paper on endoscopy was on the first flexible gastroscope5.

This capsule could replace endoscopy and allow the whole gastrointestinal tract to be visualised by transmitting images to aerials taped to the body as the capsule passes through the gastrointestinal tract. These images are stored in a recorder carried by the patient.

This invention has captured the imagination of the media with parallels made to the film Fantastic Voyage where Raquel Welch is shrunk to the size of a cell and travels throughout the body. The reality is, as yet, not quite as exciting.

The capsule cannot take pictures fast enough for the rapid transit seen during peristalsis in the oesophagus so images in this region are inferior to upper gastrointestinal endoscopy. Battery life is a problem: by the time the capsule has reached the colon it is no longer able to transmit images.

These problems can be overcome by reconfiguring the capsule so it either takes images at a faster rate or doesn't activate until it is in the colon. Changing the configuration to image one part of the gastrointestinal tract prohibits use in another area so it will be some time before the capsule can image the whole gastrointestinal tract with one swallow. The capsule is too small to carry devices that permit biopsy or therapeutic procedures.

Further developments are under way to overcome this problem and in future it is possible that limited surgical procedures will be performed from the capsule. At present the capsule is finding a role imaging the small bowel in patients with recurrent iron deficiency anaemia of unknown origin.

Almost half of patients with obscure GI bleeding and a normal endoscopy and colonoscopy will have a small bowel lesion. This part of the GI tract is difficult to access with the endoscope and radiology will miss important findings.

Wireless capsule endoscopy is discovering lesions in the small bowel missed by other investigations and is particularly useful in identifying angiodysplasia.

Therapy: undiagnosed dyspepsia

Dyspepsia is a common problem in primary care and costs the NHS up to

£1 billion each year. Patients are often referred for upper GI endoscopy to rationalise therapy and exclude serious diagnoses such as Barrett's oesophagus and malignancy. There is little evidence that endoscopy detects upper GI cancer at a treatable stage and the cost-effectiveness of Barrett's surveillance is still currently under debate.

Endoscopy may rationalise therapy as it helps distinguish between peptic ulcer disease, gastro-oesophageal reflux disease and non-ulcer dyspepsia.

We now know H. pylori causes most peptic ulcer disease and eradication therapy effects a permanent cure in most cases. A systematic review suggests H. pylori eradication will benefit a small number of patients with non-ulcer dyspepsia6.

H. pylori does not play a role in gastro-oesophageal reflux disease but this is usually diagnosed on the basis of symptomatic assessment and usually responds to treatment with proton pump inhibitors.

These observations have caused researchers to question the usefulness of endoscopy and suggest all dyspepsia patients need is a non-invasive test to screen for H. pylori and treat those infected. H. pylori negative patients can be reassured and treated empirically.

Four randomised controlled trials have shown an H. pylori test and treat strategy is as effective as endoscopy at reducing dyspepsia with substantially reduced endoscopy costs7. Some feared widespread H. pylori eradication might increase reflux symptoms in the community but randomised controlled evidence suggests this is not the case8.

The Scottish Intercollegiate Guidelines Network recently published guidelines on dyspepsia that promote H. pylori test and treat9. Interestingly this is the first guideline not to have an age cut-off at which patients with dyspepsia automatically need an early endoscopy provided they do not have alarm symptoms such as weight loss, dysphagia and anaemia. The National Institute for Clinical Excellence is developing a guideline for dyspepsia management expected in early 2004.

Recent advances in gastroenterology look exciting. Upper gastrointestinal endoscopy should become less common as it is replaced by H. pylori test and treat. This will allow expansion of lower gastrointestinal endoscopy to diagnose colorectal cancer as population screening becomes more popular.

Finally, with development of robotics it is feasible wireless capsule endoscopes will be able to perform surgical procedures within the gastrointestinal tract. Perhaps the future predicted by science fiction writers is not so fanciful after all.

Wireless capsule endoscopy is discovering lesions in the small bowel missed by other investigations~

Advantages of various screening methods

Faecal occult-blood test

Up to 20 per cent reduction in colorectal cancer motality; least expensive; most evidence for efficacy

Screening colonoscopy

Most likely to detect early cancer; high cost; increased risk of perforation

Screening flexible sigmoidoscopy

Acceptable compromise; trials incomplete; arguments over frequency and cost-effectiveness unresolved

Trials show an H. pylori

test and treat strategy is as effective as endoscopy at reducing dyspepsia~

Advances in gastroenterology

References

1.Towler B, et al. A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, Hemoccult. BMJ1998; 317:559-65

2.UK Flexible Sigmoidoscopy Screening Trial Investigators. Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet 2002; 359:1291-3000

3.Lieberman D, et al. One-time screening for colorectal cancer with combined fecal occult-blood testing and examination of the distal colon.

N Engl Med J 2001; 345:555-560

4.Iddan G, et al. Wireless capsule endoscopy.

Nature 2000; 405: 417

5.Hopkins H, et al. A flexible fiberscope using static scanning. Nature 1954; 173:39-41

6.Moayyedi P, et al. Systematic review and economic evaluation of Helicobacter pylori eradication treatment for non-ulcer dyspepsia.

BMJ 2000; 321:659-64

7.Delaney B, et al. Initial management strategies for dyspepsia (Cochrane Review). The Cochrane Library, Issue 1, 2003

8.Moayyedi P et al. The effect of Helicobacter

pylori eradication on reflux symptoms in

gastro-esophageal reflux disease in patients: a randomised controlled trial.

Gastroenterology 2001; 121:1120-26

9.No. 68. Dyspepsia. A national guideline. Scottish Intercollegiate Guidelines Network 2003. www.sign.ac.uk

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