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Recent papers on gastroenterology

GP and endoscopist Dr Huw Thomas looks at the latest papers of interest

GP and endoscopist Dr Huw Thomas looks at the latest papers of interest

Is combined oral and topical (enema) treatment with mesalazine better than oral treatment alone in patients with extensive mild or moderate ulcerative colitis?

Background

The 5-AHA drugs (for example mesalazine) have long been recommended orally for the treatment of relapses of ulcerative colitis (UC), topical treatments (enemas) generally being used for limited distal disease. When patients with UC relapse it is usual to give large doses orally. This paper questions whether the use of mesalazine enemas provide any extra benefit compared with oral treatment alone in patients relapsing with extensive disease.

The paper

Combined oral and enema treatment with mesalazine is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double-blind, placebo-controlled study. Gut. 2005;54(7):960-5.

Method A randomised, double-blind control trial was performed where 127 patients with extensive mild to moderate UC were treated with standard oral mesalazine 2g bd for eight weeks, with half also receiving a bedtime enema of 1g of mesalazine, and half a placebo enema. Disease activity was assessed by both clinical assessment and colonoscopy at four and eight weeks.

Results

Remission was achieved in 44 per cent at four weeks and 64 per cent at eight weeks in the group with the extra mesalazine enema, compared with 34 per cent and 43 per cent respectively in the placebo group.

Conclusion

Combination therapy with both oral mesalazine and nightly mesalazine enemas is superior to oral therapy alone.

What I will do now

In patients with mild and moderate relapses of their UC, not severe enough for steroid therapy, it is definitely worthwhile in combining enema (topical treatment) of a 5-AHA drug as well as continuing/increasing their oral 5-AHA regimen.

Does a negative screening colonoscopy ever need to be repeated?

Background

Colorectal cancer screening via colonoscopy is the gold standard for detection of polyps and pre-cancerous lesions to try to reduce the incidence and mortality associated with this disease. Patients who have polyps or suspicious lesions at a screening colonoscopy clearly need repeated examinations. In population-based colonoscopy colorectal screening, many patients have absolutely normal colonoscopies.Exactly what the risk of subsequent colorectal cancer developing in this low risk group is not known. If the risk is very small, and a further examination is not needed, limited resources can be better directed at screening higher risk groups.

The paper

Does a negative screening colonoscopy ever need to be repeated? Gut. 2006;55(8):1145-50.

Method

This was a population-based multicentre trial in Germany looking at participants in a colorectal screening programme. The paper estimates the risk of developing colorectal cancer according to the time since a previous negative colonoscopy, compared with the risk of colorectal cancer in patients who have never had a colonoscopy

.In this retrospective study, 380 patients who presented with colorectal cancer because of symptoms were compared with 485 controls, and their records analysed as to whether they had had a previous colonos-copy, either because of primary population screening (28 per cent), positive faecal occult blood (24 per cent) or other symptomatic reasons (48 per cent), such as irritable bowel syndrome. Patients with inflammatory bowel disease were excluded.

Results

Patients who had one negative colon-oscopy were at 74 per cent lower risk of developing colorectal cancer than patients who never had a colonoscopy. Patients with negative screening colonoscopy aged between 55 and 64 were 83 per cent less at risk than the general population, and the risk remains lower for up to 20 years.

Conclusion

Patients who have a normal colonoscopy without other risk factors can be reassured that they are unlikely to develop colorectal cancer in the future.

What I will do now

Reassure my patients without colorectal risk factors who are worried about colorectal cancer, when we discuss their normal screening colonoscopy result. The study allows me to put some figures on their risk relative to an unscreened group, and I should be able to keep them away from colonoscopists for a decade or so at least, unless they are unfortunate to develop any alarm symptoms, such as rectal bleeding.

Does 4g of paracetamol a day affect liver transaminases (ALT) in normal individuals?

Background

GPs regularly prescribe paracetamol (acetaminophen) to patients in doses of up to eight tablets (4g) daily – particularly for elderly arthritic patients. We should not be surprised if our patients develop abnormal LFTs, but this study compares groups of healthy individuals who only differ in their paracetamol ingestion (therapeutic levels).

The paper

Aminotransferase elevations in healthy adults receiving 4g acetaminophen daily: a randomised controlled trial. JAMA. 2006;5;296(1):87-93.

Method

This was a randomised, single-blind, placebo-controlled longitudinal study of 145 healthy adults in a pharmacology laboratories. They were randomised into a placebo group or to a paracetamol group, or to one of three combination opioid drugs containing paracetamol. Their diet was controlled carefully and LFTs measured together with peak and trough paracetamol levels daily over eight days, and then every other day until they completed 14 days' treatment.

Results

None of the patients on placebo had ALT changes more than three times normal levels, but 31-44 per cent of patients receiving paracetamol or paracetamol in combination with an opioid had a maximum ALT of more than three to four times normal. The coprescribing of an opioid did not seem to influence this effect.

Conclusion

Regular daily intake of 4g/day of paracetamol is associated with elevated ALT in healthy adults.

What I will do now

In view of the frequency of paracetamol use as an analgesic in maximal doses, I will be more alert to changes in ALT levels, and measure LFTs intermittently in these patients. I will be particularly careful in patients known to be taking 4g/day and reduce this dose or just use a codeine-based analgesic where abnormal LFTs are found.

How should GPs manage chronic constipation in children?

Background

This is a very common scenario in primary care. It accounts for about a quarter of a paediatric gastroenterologist's workload and is a common reason for referral to paediatric departments. Most cases are functional (90-95 per cent), and this paper attempts to give a management plan based on a synthesis of current guidelines.

The paper

Chronic constipation in children. Clinical Review. BMJ. 2006;333:1051-55.

Method

This review article updates the 2002 clinical evidence systematic review, supplementing the 2002 evidence with more recent randomised control trials or systematic reviews. It is written for GPs and non-specialists, and emphasises the lack of evidence for available treatments.

Results Neither osmotic laxatives nor stimulant laxatives, nor increased fibre diets have any placebo-controlled, randomised trials to back up their use. Biofeedback has had poor results, actually showing a marginal (although not significant) increase in faecal incontinence after 12 months treatment as an adjunct to laxatives.

Behaviour modification used in addition to laxatives did improve rates of soiling at three and 12 months. Rewarding successful toilet use is better than rewarding 'staying clean'. Guidelines are based mainly on consensus and experience.

Conclusion

Constipation treatments in children have little evidence to confirm their efficacy. Management plans are most likely to succeed if they try to reduce child and parent anxiety, remove initial faecal impaction, and support the child in restoring a regular routine that involves regular passing of soft stool without pain. Ongoing support may be needed over months or years.

What I will do now

Rather than just prescribing laxatives (for dis-impaction) over the telephone, I will meet with parents and child to try to reassure and initiate behaviour change with regular unhurried toileting and rewarding successful toilet use. I will only do blood tests (inflammatory markers, coeliac screen, thyroid function, calcium and glucose) where I suspect an organic cause or in resistant cases prior to specialist referral, and involve the health visitor for ongoing support.

How to manage patients with cirrhosis and ascites?

Background

Mortality from cirrhosis was 12.7 per 100,000 in 2000. Ascites will develop in about half of patients who have cirrhosis followed over 10 years, and is an important landmark as 50 per cent will be dead within a further two years. Three-quarters of patients with ascites will have cirrhosis, usually caused by non-alcoholic fatty liver disease, alcohol abuse or hepatitis C.

The paper

Guidelines on the management of ascites in cirrhosis. Gut. 2006;55 (Suppl 6):vi1-vi12.

Method

The guidelines were produced by the British Society of Gastroenterology, and based on a comprehensive literature search of randomised control trials and systematic reviews. Where this was not available, the authors took evidence from expert committee reports.

Key points

The management of ascites has changed considerably over recent years. There is now a better understanding of the pathogenesis of ascites, with the relative roles of portal hypertension and sodium and water retention more clearly understood.

Dietary salt restriction (no added salt diet) and diuretics (spironolactone) remain first-line, but furosemide and loop diuretics should only be used when maximum doses of spironolactone have been reached, and then only in moderate doses (up to 160mg/day). Patients now often undergo repeated therapeutic paracentesis to control their ascites, generally the fluid being completely drained on each occasion. The paper also emphasised the importance of recognising spontaneous bacterial peritonitis, which is an important complication of patients with ascites. It can present with non-specific symptoms such as fever, mild abdominal pain, vomiting or increasing confusion, and needs urgent hospitalisation and intravenous antibiotics.

What I will do now

I occasionally look after patients with terminal cirrhosis and ascites in our local GP hospital. The guidelines clarify the role for diuretics, and emphasise the importance of spironolactone as the first-line diuretic treatment (furosemide is very much second line).

I have also had to perform therapeutic paracentesis and the guidelines clarify when this is appropriate. It emphasises the importance of keeping the whole procedure a strictly sterile one, removing all the fluid at one go rather than using a number of smaller procedures, and the role of volume expanders afterwards. I will also be alert to the possibility of spontaneous bacterial peritonitis in patients with ascites.

Dr Huw Thomas is a part-time GP in Minehead, Somerset, and a clinical assistant in the endoscopy and minor injuries unit at Minehead Hospital – he is also a GP trainer and a member of the Primary Care Society for Gastroenterologists

Competing interests

Dr Thomas has occasionally received grants towards attending international scientific meetings from a number of pharmaceutical companies

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