Abstract
Introduction
Diverticula (mucosal outpouching through the wall of the colon) affect over 5% of adults aged 40 years and older, but only 10-25% of affected people will develop symptoms such as lower abdominal pain. Recurrent symptoms are common, and 5% of people with diverticula eventually develop complications such as perforation, obstruction, haemorrhage, fistulae, or abscesses.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of: treatments for uncomplicated diverticular disease; treatments to prevent complications; and treatments for acute diverticulitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 13 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antispasmodics, bran, elective surgery, increasing fibre intake, ispaghula husk, lactulose, medical treatment, mesalazine, methylcellulose, rifaximin, surgery.
Key Points
Diverticula (mucosal outpouching through the wall of the colon) affect over 5% of adults aged 40 years and older, but only 10-25% of affected people will develop symptoms such as lower abdominal pain.
Recurrent symptoms are common, and 5% of people with diverticula eventually develop complications such as perforation, obstruction, haemorrhage, fistulae, or abscesses.
Use of non-steroidal anti-inflammatory drugs, corticosteroids, and opiate analgesics have been associated with an increased risk of perforation of diverticula, while calcium antagonists may protect against these complications.
Dietary fibre supplementation, and laxatives such as methylcellulose and lactulose are widely used to treat uncomplicated diverticular disease, but we don't know whether they reduce symptoms or prevent complications.
Antibiotics (rifaximin) plus dietary fibre supplementation may improve symptoms more than fibre alone, but increase the risk of adverse effects.
We don't know whether mesalazine is also beneficial at improving symptoms in uncomplicated diverticular disease, or at reducing complications after acute diverticulitis, as no good-quality studies have been found.
We don't know whether elective open or laparoscopic colonic resection improve symptoms in people with uncomplicated diverticular disease.
Acute diverticulosis is often treated with intravenous fluids, limiting oral intake, and broad spectrum antibiotic use. However, we don't know whether such medical treatment improves symptoms and cure rates in people with acute diverticulitis.
Surgery is usually performed for people with peritonitis caused by perforated acute diverticulitis, but we don't know whether it improves outcomes compared with no surgery, or if any one surgical technique is better at preventing complications.
About this condition
Definition
Colonic diverticula are mucosal outpouchings through the large bowel wall. They are often accompanied by structural changes (elastosis of the taenia coli, muscular thickening, and mucosal folding). They are usually multiple, and occur most frequently in the sigmoid colon. The majority of people with colonic diverticula are asymptomatic, with little to find on clinical examination, while 20% develop symptoms at some point. If diverticula are associated with symptoms, then this is termed diverticular disease. If asymptomatic, then the condition is known as diverticulosis. People who go on to develop complications associated with diverticula (inflammation, perforation, fistulae, abscess formation, obstruction, or haemorrhage) are referred to as having complicated diverticular disease. People with uncomplicated diverticular disease may report abdominal pain (principally colicky left iliac fossa pain), bloating, and altered bowel habit, and may have mild left iliac fossa tenderness on examination. Acute diverticulitis occurs when a diverticulum becomes acutely inflamed. People with acute diverticulitis typically present with severe left iliac fossa pain associated with fever, malaise, and altered bowel habit with left iliac fossa tenderness, associated with general signs of infection, such as fever and tachycardia.
Incidence/ Prevalence
In the UK the incidence of diverticulosis increases with age; about 5% of people are affected in their fifth decade of life, and about 50% by their ninth decade. Diverticulosis is common in resource-rich countries, although there is a lower prevalence of diverticulosis in Western vegetarians consuming a diet high in fibre. Diverticulosis is almost unknown in rural Africa and Asia.
Aetiology/ Risk factors
There is an association between low-fibre diets and diverticulosis of the colon. Prospective observational studies have found that both physical activity and a high-fibre diet are associated with a lower risk of developing diverticular disease. Case control studies have found an association between perforated diverticular disease and non-steroidal anti-inflammatory drugs, corticosteroids, and opiate analgesics, and have found that calcium antagonists have a protective effect. People in Japan, Singapore, and Thailand develop diverticula that affect mainly the right side of the colon.
Prognosis
Inflammation will develop in 10-25% of people with diverticula at some point. It is unclear why some people develop symptoms and some do not. Even after successful medical treatment of acute diverticulitis, almost two thirds of people suffer recurrent pain in the lower abdomen. Recurrent diverticulitis is observed in 7-42% of people with diverticular disease, and after recovery from the initial attack the calculated yearly risk of suffering a further episode is 3%. About 50% of recurrences occur within 1 year of the initial episode, and 90% occur within 5 years. Complications of diverticular disease (perforation, obstruction, haemorrhage, and fistula formation) are each seen in about 5% of people with colonic diverticula when followed up for 10-30 years. In the UK, the incidence of perforation is four cases per 100,000 people a year, leading to approximately 2000 cases annually. Intra-abdominal abscess formation is also a recognised complication.
Aims of intervention
To reduce mortality, symptoms, and complications, with minimal adverse effects.
Outcomes
Subjective gastrointestinal symptoms assessed by the use of questionnaires; admission and readmission rates as a result of diverticular disease and its complications; and mortality. For the question about the effect of treatments for preventing recurrence and complications of diverticular disease, the primary outcomes of interest are as follows: incidence of diverticulitis, haemorrhage, perforation, abscess, fistula formation, and mortality from these complications. Stool weight and transit time are surrogate outcomes.
Methods
BMJ Clinical Evidence search and appraisal March 2007. The following databases were used to identify studies for this systematic review: Medline 1986 to March 2007, Embase 1986 to March 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2007, Issue 1. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE). We also searched for retractions of studies included in the Review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. The authors also performed their own search of Medline in July 2006. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies.Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single blinded, and containing more than 40 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We also did a search for cohort studies on specific harms of interventions. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).
Table.
GRADE evaluation of interventions for colonic diverticular disease
Important outcomes | Symptom relief, recurrence, mortality, adverse effects | ||||||||
Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
What are the effects of treatments for uncomplicated diverticular disease? | |||||||||
1 (76) | Symptom relief | Bran and ispaghula husk v placebo | 4 | –3 | –1 | –1 | 0 | Very low | Quality points deducted for poor follow-up, uncertainty of number of participants receiving treatment, sparse data, and no intention-to-treat analysis. Consistency point deducted for conflicting results. Directness point deducted for uncertainty about disease states |
1 (30) | Symptom relief | Methylcellulose v placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for uncertainty about other disease states |
1 (43) | Symptom relief | Lactulose v placebo | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for sparse data. Directness points deducted for uncertainty about definition of outcome or other disease states |
2 (1136) | Symptom relief | Rifaximin plus dietary fibre supplementation v dietary supplementation | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
1 (170) | Symptom relief | Mesalazine v rifaximin | 4 | –3 | –1 | –1 | 0 | Very low | Quality points deducted for sparse data, methodological flaws (randomisation/blinding flaws), and incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for uncertainty about intermittent use of comparator |
What are the effects of treatments to prevent complications of diverticular disease? | |||||||||
1 (166) | Recurrence of symptoms | Mesalazine v no treatment | 4 | –2 | 0 | –2 | 0 | Very low | Quality points deducted for sparse data and poor follow-up. Directness point deducted for unclear measurement of outcomes and inclusion of intervention |
What are the effects of treatments for acute diverticulitis? | |||||||||
1 (51) | Cure rates | Medical treatment v each other | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data. Directness point deducted for few comparators |
1 (62) | Mortality | Acute sigmoid colonic resection v no acute resection | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for conflicting results in subgroup analysis |
1 (62) | Postoperative complications | Acute sigmoid colonic resection v no acute resection | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
1 (105) | Mortality | Primary v secondary sigmoid colonic resection | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
1 (105) | Postoperative complications | Primary v secondary sigmoid colonic resection | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion.Consistency: similarity of results across studies. Directness: generalisability of population or outcomes. Effect size: based on relative risk or odds ratio.
Glossary
- Acute diverticulitis
This condition occurs when a diverticulum becomes acutely inflamed. There may be general symptoms and signs of infection (including fever and rapid heart rate) with or without local symptoms and signs (pain and localised tenderness, usually in the lower left abdomen, sometimes with a mass that can be felt on abdominal or rectal examination).
- Acute sigmoid colonic resection
Immediate resection of the sigmoid colon, involving end colostomy of the proximal bowel and creating a mucus fistula with the distal bowel or oversewing the rectal stump.
- Defunctioning colostomy
Stoma created to divert faecal flow, such that faeces no longer flow through the anus.
- Diverticular disease
This term is used to describe diverticula associated with any symptoms. Symptoms commonly include abdominal pain and alteration in bowel habit. Diverticular disease may be complicated by abscess formation, fistulae, perforation, obstruction, or haemorrhage.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Rifaximin
A rifamycin antibacterial drug with antimicrobial actions similar to those of rifampicin. It is marketed predominantly in Italy.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Mr David Humes, Department of Surgery, University of Nottingham, Nottingham, UK.
Mr John Simpson, Department of General Surgery, University Hospital Nottingham, Nottingham, UK.
Professor Robin C Spiller, Division of Gastroenterology, University Hospital Nottingham, Nottingham, UK.
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