The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.

AIM: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS: All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.

Crohn's disease for the general physician: presentation and investigations.

Crohn's disease presents to general physicians in a variety of ways. This article outlines the clinical features and initial investigation of suspected Crohn's disease. The accompanying article reviews treatment strategies.

Crohn's disease for the general physician: management.

Crohn's disease presents to general physicians in a variety of ways. The previous article outlined clinical features and initial investigations, and this article covers management of Crohn's disease, including monitoring and drug toxicity.

Natural history of Crohn's disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates.

INTRODUCTION: Benefits of immunosuppressive therapy in Crohn's disease have been demonstrated in controlled trials; however, it is unclear whether these drugs alter the longer-term natural history of this condition. AIMS AND METHODS: To assess changes in disease outcomes in a population-based cohort of patients diagnosed in Cardiff from 1986 to 2003. Case notes from Crohn's disease incidence studies in Cardiff were reviewed retrospectively for disease characteristics and follow-up information on drug therapy, and the need for surgery for Crohn's disease. The study population was divided into three groups by year of diagnosis (Group A=1986-1991, Group B=1992-1997 and Group C=1998-2003). RESULTS: 341 patients were included. Kaplan-Meier (KM) analysis showed increasing use of immunosuppressants over time. At 5 years after diagnosis this was 11% in Group A, 28% in Group B, and 45% in Group C (p=0.001) and the median time to start of thiopurines was 77, 21 and 11 months in Group A, B and C respectively. There was a significant reduction in long-term steroid use at 5 years post diagnosis: 45 (44%), 31 (31%) and 24 (19%) patients in Group A, B and C respectively (p=0.001). KM analysis showed a significant reduction in the cumulative probability of intestinal surgery: At 5 years this was 59% (Group A), 37% (Group B) and 25% (Group C) (p=0.001). In a multivariate Cox analysis, year of diagnosis, disease location, oral corticosteroids within 3 months of diagnosis and early thiopurine use (within the first year of diagnosis) were all independent factors affecting likelihood of intestinal surgery. CONCLUSION: This population-based cohort shows marked changes in rates of surgery, and the reduction is independently associated with year of diagnosis, and associated temporally with increased and earlier thiopurine use.

Managing immunosuppression in medical patients.

Immunosuppressive drugs are increasingly widely used. Safe use requires knowledge of the side-effect profile, contraindications and precautions before starting, and the monitoring regimen, and patients should be fully informed of the risks and benefits before starting.

Review article: medication non-adherence in ulcerative colitis--strategies to improve adherence with mesalazine and other maintenance therapies.

BACKGROUND: Significant number of patients with ulcerative colitis (UC) fail to comply with treatment. AIMS: To review issues surrounding medication non-adherence in inflammatory bowel disease (IBD), including the clinical and health service implications in the UK, and discuss strategies for optimizing medication adherence. METHODS: Articles cited were identified via a PubMed search, utilizing the words IBD, adherence, compliance, medication and UC. RESULTS: Medication non-adherence is multifactorial involving factors other than dosing frequency. Male gender (OR: 2.06), new patient status (OR: 2.14), work and travel pressures (OR: 4.9) and shorter disease duration (OR: 2.1), among others are proven predictors of non-adherence in UC. These indicators can identify 'at-risk' patients and allow an individually tailored treatment approach to be introduced that optimizes medication adherence. A collaborative relationship between physician and patient is important; several strategies for improving adherence have been proven effective including open dialogue that takes into consideration the patient's health beliefs and concerns, providing educational (e.g. verbal/written information, self-management programmes) and behavioural interventions (e.g. calendar blister packs, cues/reminders). CONCLUSIONS: Educational and behavioural interventions tailored to individual patients can optimize medication adherence. Additional studies combining educational and behavioural interventions may provide further strategies for improving medication adherence rates in UC.

The incidence of Crohn's disease in Cardiff over the last 75 years: an update for 1996-2005.

BACKGROUND: The incidence of Crohn's disease rose rapidly in industralized countries over the past 50 years, but it is unclear whether the incidence is still rising or has reached a plateau. AIMS: To update the long-term incidence study of Crohn's disease in Cardiff for 1996-2005, to investigate whether incidence is still rising and to study changes in disease characteristics over time. METHOD: Crohn's cases identified by retrospective analysis of hospital records as in previous studies in Cardiff. RESULTS: Two hundred and twelve cases were identified. Corrected incidence for this decade was 66 x 10(6) per year (95% confidence interval: 58-76), showing a continuing rise compared to previous decades. The proportion with colonic disease at presentation continues to rise (43%) with a corresponding fall in those with terminal ileal disease. There remains a strong female preponderance (F:M 1.6:1) as in previous studies. The incidence in children under age 16 continues to rise, and the median age at diagnosis has fallen slightly. CONCLUSION: Crohn's disease incidence continues to rise slowly in Cardiff with a continuing increase in those presenting with colonic disease, which is now the commonest disease pattern.

A randomized, double-blind, placebo-controlled trial of lenalidomide in the treatment of moderately severe active Crohn's disease.

BACKGROUND: Therapy targeted at tumour necrosis factor-alpha has an established role in Crohn's disease. Lenalidomide, an analogue of thalidomide, is an oral immunomodulatory agent with powerful antitumour necrosis factor-alpha properties. It is licensed for myeloma and myelodysplastic syndrome. Based upon reports of thalidomide efficacy, lenalidomide was evaluated in Crohn's disease. AIM: To evaluate the efficacy and safety of lenalidomide in subjects with moderately severe active Crohn's disease. METHODS: In a multicentre, double-blind, placebo-controlled parallel group study 89 subjects were randomized to lenalidomide 25 mg daily, 5 mg daily or placebo. Subjects were treated for 12 weeks. The primary end point was a 70-point reduction in Crohn's Disease Activity Index. RESULTS: The overall clinical response rate was not significantly different between the three groups: lenalidomide 25 mg 26%, lenalidomide 5 mg 48% and placebo 39%. Lenalidomide was generally well tolerated with only one serious adverse event, a deep vein thrombosis, being attributed to treatment. CONCLUSION: Lenalidomide, an oral agent with antitumour necrosis factor-alpha properties, was not effective in active Crohn's disease in contrast to reports of benefit from thalidomide. The reasons for this lack of efficacy are speculative, other physiological activities may offset its action on inflammatory cytokines, or its antitumour necrosis factor-alpha action without apoptosis may be insufficient for activity in Crohn's disease.

Review article: how and when to use ciclosporin in ulcerative colitis.

Although colectomy for ulcerative colitis is curative, long-term quality of life is reduced. Intravenous ciclosporin 4 mg/kg/day has significant toxicity. There is now evidence that low-dose ciclosporin (2 mg/kg daily by intravenous infusion, or 5-6 mg/kg daily in a twice daily oral dosage) has an acceptable safety profile, even when used in combination with corticosteroids. Drug dosage should be adjusted to the levels of 150-250 ng/mL initially (random levels during intravenous infusion, or trough levels for oral use). Ciclosporin should be considered not only in those who have failed 7 days of corticosteroids, but also in fulminant colitis at day 3, if not responding to corticosteroids. The drug should be avoided in frail or elderly patients with significant comorbidity, and also where colectomy is likely to be necessary in the short to medium term. Ciclosporin should not be continued for more than 7 days, unless there is a definite response. A 70-80% initial response is likely, and responders are discharged on oral ciclosporin, adding thiopurines and tailing prednisolone rapidly. The drug should be continued for 3 months. The likelihood of avoiding colectomy over 2-3 years is 40-50%. More studies are needed to evaluate the use of oral ciclosporin in corticosteroid-refractory colitis in out-patients, and to assess whether monotherapy (without corticosteroids) is significantly safer, without loss of efficacy.

Diagnostic accuracy of faecal calprotectin estimation in prediction of abnormal small bowel radiology.

BACKGROUND: [corrected] Patients being investigated for symptoms of abdominal pain, diarrhoea and or weight loss often undergo small bowel radiology as part of their diagnostic workup mainly to exclude inflammatory bowel disease. AIM: To assess and compare the utility of a single faecal calprotectin estimation to barium follow through as well as conventional inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein in exclusion of intestinal inflammation. METHODS: Seventy-three consecutive cases undergoing barium follow through for investigation of symptoms of diarrhoea and or abdominal pain with or without weight loss were studied. The control group comprised 25 cases with known active Crohn's disease (positive controls), 26 normal healthy volunteers (negative controls) and 25 cases of irritable bowel syndrome diagnosed by Rome II criteria. Symptoms, erythrocyte sedimentation rate and C-reactive protein were recorded at recruitment and a single stool sample assayed for calprotectin within 7 days prior to or after barium follow through. RESULTS: The median calprotectin value in the active Crohn's group, irritable bowel syndrome group and normal volunteers was 227 microg/g of stool, 19 and 10 microg/g respectively (P < 0.0001). A faecal calprotectin above a cut-off value of 60 microg/g was able to predict all nine cases with an abnormal barium follow through as well as all six cases with a normal barium follow through but with organic intestinal disease. The negative predictive value of a single calprotectin result below 60 microg/g of stool was 100% compared with 91% each for erythrocyte sedimentation rate > 10 mm and C-reactive protein > 6 mg/L and 84% for a combination of erythrocyte sedimentation rate and C-reactive protein in predicting absence of organic intestinal disease. CONCLUSION: A single stool calprotectin value < 60 microg/g of stool obviates the need for further barium radiology of the small bowel, is more accurate than measurement of erythrocyte sedimentation rate or C-reactive protein and effectively excludes Crohn's disease or non-functional gastrointestinal disease.

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy--a prospective, randomised, double-blind trial.

BACKGROUND: Peristomal infection can sometimes complicate percutaneous endoscopic gastrostomy (PEG) placement. Antibiotic prophylaxis has, in some studies, been shown to reduce the incidence. However, the use of prophylaxis varies widely, possibly because the design and findings of the studies have differed, making their relevance to clinical practice difficult to interpret. AIM: To determine the efficacy of antibiotics, either prophylaxis or concurrent antibiotics at the time of the procedure, in reducing peristomal infection after PEG insertion in the context of a study designed to reflect current practice. METHODS: One hundred and forty-one patients undergoing PEG placement were randomised to group one to receive either a single dose of 750 mg of intravenous cefuroxime (n=50) or placebo (n=51) 30 min before PEG insertion. Forty patients who, for various reasons, were already receiving antibiotics were allocated to group two. The peristomal site was evaluated on day 3, 5 and 7 following insertion. Erythema and exudate were scored on a scale from 0 to 4; induration was scored on a scale of 0-3. A maximum combined score of 8 or higher or the presence of pus was criteria for infection. The primary outcome measure was the occurrence of a peristomal wound infection at any time within one week of PEG insertion. RESULTS: Peristomal wound infection was significantly reduced in patients who received antibiotics either as a single dose of cefuroxime [one of 33 (3%)], or in those on antibiotics for prior indications [one of 36 (3%)], compared with placebo [six of 33 (18%)], P=0.04 and 0.03, respectively. CONCLUSION: Antibiotics, either prophylaxis or concurrent, reduce the incidence of peristomal wound infection after PEG placement.

Naloxone treatment for irritable bowel syndrome--a randomized controlled trial with an oral formulation.

BACKGROUND: Opioids change gut motility and secretion, causing delayed intestinal transit and constipation. Endorphins play a role in the constipation troubling some patients with irritable bowel syndrome; hence naloxone, an opioid antagonist, may have a therapeutic role. AIM: To assess the efficacy and safety of an oral formulation of naloxone in irritable bowel syndrome patients with constipation. METHODS: A randomized, double-blind, placebo-controlled trial was performed. Patients fulfilling the Rome II criteria for irritable bowel syndrome (constipation-predominant and alternating types) were randomized to receive 8 weeks of treatment with naloxone capsules, 10 mg twice daily, or identical placebo. RESULTS: Twenty-eight patients entered the study, which was completed by 25. 'Adequate symptomatic relief' was recorded in six of 14 on naloxone and three of 11 on placebo. Whilst the differences were not significant, improvements in severity gradings and mean symptom scores for pain, bloating, straining and urgency to defecate were greater with naloxone than placebo for all parameters. In addition, quality of life assessments improved to a greater extent in patients taking naloxone. CONCLUSIONS: Preliminary results suggest that naloxone is well tolerated and beneficial in patients with irritable bowel syndrome and constipation. A larger clinical trial is needed to provide sufficient statistical power to assess efficacy.

Enteric-release glyceryl trinitrate in active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Mucosal ischaemia may contribute to the pathogenesis of Crohn's disease. Microvascular abnormalities have been found in colonic resection specimens, and mucosal levels of constitutive nitric oxide synthase are reduced. AIM: To assess the efficacy of a novel, enteric-release formulation of the nitric oxide donor, glyceryl trinitrate, aimed at increasing the mucosal circulation and relaxing smooth muscle in the affected bowel. METHODS: The trial was randomized, double-blind and placebo-controlled. Baseline disease activity was assessed by a structured symptom diary, with blood tests and a quality of life assessment. Patients with a Crohn's disease activity index of > or = 150 and < 450 were randomized to receive 12 weeks of either glyceryl trinitrate (initially 6 mg twice daily, increasing to 9 mg twice daily after 6 weeks) or an identical placebo. Assessments were repeated at 6 and 12 weeks. RESULTS: Seventy patients (22 male) entered the study; 34 were given glyceryl trinitrate and 36 placebo. At 12 weeks, there were no differences between the treatment groups in terms of Crohn's disease activity index, pain, stool frequency, inflammatory markers or quality of life scores. CONCLUSIONS: Enteric-release glyceryl trinitrate did not benefit patients with mild to moderately active Crohn's disease. Whilst ischaemia may contribute to the pathogenesis of Crohn's disease, our results fail to provide supportive evidence for this hypothesis.

Measles, month of birth, and Crohn's disease.

BACKGROUND: The rise in the incidence of Crohn's disease (CD) suggests the role of an environmental factor in the development of the disease in susceptible individuals. Perinatal exposure to infection has been proposed as such an environmental factor. AIM: To investigate the influence of birth date on the development of CD in later life. PATIENTS AND METHOD: Four registers of patients with CD, diagnosed from 1972 to 1989, were combined, and data from 1624 patients were examined. The birth dates of CD patients were compared with national birth figures for three decades (1941-50, 1951-60, and 1961-70) to avoid temporal changes in birth trends, and year of birth was compared with epidemic measles years between 1951 and 1967. Risk ratios with 95% confidence intervals (CI) and chi(2) tests were performed. RESULTS: There were marginal differences between the birth dates of the CD patients and those predicted from the general population. Further analysis of both season of birth and year halves revealed a very weak association with the first half of the year (relative risk 1.14 (95% CI 1.01-1.30)). There was no association between developing CD and birth during measles epidemics between 1951 and 1967. CONCLUSIONS: In utero or perinatal exposure to seasonal environmental factors are unlikely potential aetiological agents in the later development of CD.