Introduction Retrospective studies have confirmed that colonic investigations may miss a diagnosis of colorectal cancer (CRC) with a wide variation in reported miss rates.1 2 Colorectal cancer miss rates of up to 12%, 22% and 50% have been reported for colonoscopy, barium enema and sigmoidoscopy, respectively. Methods A retrospective study was conducted to determine the diagnostic miss rate of colorectal cancer at our institution. All patients diagnosed with colonic or rectal adenocarcinoma between 2006 and 2010 were identified from the Royal Liverpool and Broadgreen University Hospital Trust histopathology database. Data were collected using the computerised systems and case notes. A miss was defined as a patient investigated with barium enema (BE), CT abdo-colon enhanced (CTACE), CT colonoscopy (CTC), flexible sigmoidoscopy and/or colonoscopy, and discharged without being followed-up or diagnosed with CRC in the 5 years preceding the subsequent CRC diagnosis. Results During the study period, 579 patients were diagnosed with colorectal cancer. The notes were irretrievable or had insufficient documentation in 5 cases. Twenty-two (3.8%) cases were considered misses: 5 (0.8%) were administrative misses, where patients were lost to follow-up, or they cancelled or failed to attend an appointment; in one case (0.2%), there was a clinician-associated miss, where an inappropriate choice of investigation was performed (a flexible sigmoidoscopy missed a proximal CRC); and 16 (2.8%) were technical misses, where CRC was missed with an appropriate choice of investigation. Of the technical misses, 10 (1.7%) were radiological (0.7%, 0.7% and 0.3% for BE, CTACE and CTC respectively) and 8 (1.4%) were endoscopic (0.5% and 0.9% for flexible sigmoidoscopy and colonoscopy). 45% of missed cancers were left-sided and below the splenic flexure. Conclusion This study has shown a lower miss rate in our institution than previously reported,3 and when compared with other studies. Competing interests None declared. References 1. Frenette CT, Strum WB. Relative rates of missed diagnosis for colonoscopy, barium enema, and flexible sigmoidoscopy in 379 patients with colorectal cancer. J Gastrointest Cancer 2007;38:148–53. 2. Somasekar A, James L, Stephenson BM, et al. The value of auditing negative lower GI investigations preceding a final diagnosis of colorectal cancer. Colorectal Dis 2009;11:740–4. 3. Graham M, et al. Endoscopy 2005;37:A275.

Aliment Pharmacol Ther 2011; 34: 1282–1294 Summary Background Several published studies have evaluated the efficacy of tacrolimus in the management of Crohn’s disease with variable conclusions. Aim To review systematically the evidence examining the efficacy and safety of tacrolimus in treating Crohn’s disease. Methods The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PUBMED) and EMBASE (1984 to January 2011) were searched. Also, references from selected articles were examined. Case series (five or more patients), cohort and randomised controlled trials were eligible for inclusion, incorporating oral, intravenous or topical tacrolimus therapy. The primary outcome was induction of remission of active Crohn’s disease. Results Eleven studies met the inclusion criteria which included 163 patients, of which 127 received tacrolimus therapy. In patients with luminal Crohn’s disease, the crude pooled remission rate for tacrolimus was 44.3% (range, 7–69%) and the crude pooled response rate was 37.1% (range, 14–57%). For patients with perianal disease using systemic tacrolimus, crude pooled remission rate was 28.6% (range, 0–64%) and crude pooled response rate was 38.8% (range, 0–57%). Combining data from two studies using topical tacrolimus, 35.7% of patients achieved remission and 28.6% partial response. Nonserious adverse effects are common, particularly tremor, paraesthesia and headache. Reversible nephrotoxity occurred in 16% of patients. Conclusions The current evidence; although of a poor quality, appears to support the use of tacrolimus in Crohn’s disease. High quality randomised controlled trials are needed.

Background: The benefits of a well-managed transition for adolescents with inflammatory bowel disease (IBD) are being increasingly recognized. However, there is limited evidence to support effective means of transition. Patient feedback is important to establish the value of such services. This survey looks at how young people with IBD and their families perceived the effectiveness of a model of transition and what improvements were needed. Design: Postal questionnaire survey. Setting: Transition between paediatric services at Alder Hey Children′s NHS Foundation Trust, Liverpool and the Royal Liverpool University Hospital (adult centre). Population: Young people (adolescents) who had been through the transition process between the above centres from 2003-2008. Interventions: A semi-structured questionnaire survey designed to obtain patient feedback on transition care arrangements and provision of service. Main outcome measures: Patient information, satisfaction and suggestions. Results: 35 of 66 families returned the questionnaire. High rates of satisfaction were reported (33/35; P<0.001-sign test). Feedback included provision of adequate information, opportunity to discuss change (P<0.001) and reduction in perceived anxiety about the transfer (P=0.08).Conclusions: High rates of satisfaction with transition incorporating a pre-transfer meeting were expressed

Introduction Acute severe ulcerative colitis (UC) is a medical emergency requiring hospitalisation. Approximately one third of patients will not respond to therapy and will need colectomy during the hospital admission. Data examining mortality, efficacy of therapy, treatment selection and outcomes often come from specialised units with relatively few data examining outcomes in larger less selected populations. The UK National IBD Audit collected data on over 6000 adult patients admitted to UK hospitals with IBD. Aim To assess outcomes for patients with acute severe ulcerative colitis in the 2008 National IBD Audit. Methods All hospitals that admitted IBD patients in the UK were invited to take part. Sites completed a questionnaire detailing service at 1 September 2009. Sites were asked to audit 40 set of case notes of patients that were admitted with IBD between 1/09/07 and 31/08/08. Acute severe UC was defined by the Truelove and Witts criteria. Results 209 sites submitted data, with a 93% participation at Trust/Health board level. Data were collected on 6135 patients (3154 CD and 2981 UC). Of the 2981 patients with UC, there were 863 with acute severe disease (465 males, median age 41 years (IQR 28–58 years). Inpatient mortality was 1.2% with death being strongly associated with increased age (p<0.001), male sex (p=0.02), C. Diff infection (p<0.04) and if first line medical treatment fails the risk of death increases to 2.8%. 61.1% responded to first line treatment with steroids. Of the 317 who failed treatment with steroids 108 underwent surgery without further medical treatment, 98 were treated with cyclosporine and 52 with infliximab. The response rate to infliximab was higher than that to cyclosporine (75% vs 46%, p=0.0009). Overall 163 underwent surgery with a median time to surgery of 10 days (IQR 7–14 days). The post operative mortality did not differ between those coming to surgery before and after 7 days following admission. Conclusion The inpatient mortality of acute severe UC in the UK remains appreciable and strongly associated with age and the presence of C. Diff infection. The risk of death doubles if first line medical therapy fails. In this data set, response rates to infliximab are greater than cyclosporin although the results of ongoing clinical trials will give further data. Effective communication between medical and surgical teams, clear decision making and timely surgery will help keep mortality to a minimum.

SummaryBackground Crohn’s disease is characterized by defective innate immune responses to intestinal bacteria. Clarithromycin is a broad‐spectrum antibiotic that has good penetration into macrophages.Aim To assess the efficacy of clarithromycin in active Crohn’s disease.Methods Patients with Crohn’s disease activity index > 200 and serum C‐reactive protein ≥ 10 mg/L were randomized to receive clarithromycin 1 g o.d. or placebo for 3 months. Patients taking more than 10 mg/day prednisolone or 3 mg/day budesonide were excluded. Primary outcome was remission (CDAI ≤ 150) or response (fall in CDAI ≥ 70 from pre‐treatment level) at 3 months.Results The trial was stopped after 41 patients had been recruited because of poor overall efficacy. There was no difference in combined remission or response rates at 3 months between clarithromycin: 26% (five of 19) and placebo: 27% (six of 22) (P = 1.00). The mean (s.d.) fall in Crohn’s disease activity index was 35 (80) clarithromycin and −2 (114) placebo (P = 0.24). However, post hoc analysis showed a significant difference in response/remission determined by Crohn’s disease activity index after 1 month: 53% (10 of 19) clarithromycin vs. 14% (three of 22) placebo (P = 0.01).Conclusion Clarithromycin 1 g for 3 months is ineffective in active Crohn’s disease but possible benefit was observed at 1 month, suggesting that an initial effect may be attenuated by subsequent bacterial resistance.

Late complications of pelvic radiotherapy occur in 5-20% of patients, particularly chronic radiation proctitis (CRP). Rectal bleeding is the most common symptom. Other symptoms include difficulty in defaecation or tenesmus because of loss of distensibility of the rectum or rectal structuring. Treatment options of CRIP include oral therapy (5-aminosalicylates, metronidazole), rectal instillation therapy (hydrocortisone, sucralfate, 5-aminosalicylates, formalin), thermal therapy (argon plasma coagulation, heater probe or laser) and hyperbaric oxygen. It is difficult to recommend evidence-based therapy. There are no adequately powered studies of the treatment of CRP and most data are uncontrolled, non-blinded observation studies from single sites. There are no standard evaluation tools (including endoscopic grading, symptom scores and quality-of-life scores), adequate description of preceding radiotherapy dose or adequate follow-up in most studies. Many studies have poor documentation of complications and few are carried out prospectively. A pragmatic approach is to use sucralfate enemas and oral metronidazole. Thermal methods seem to be effective and safe. Simple heater probe treatment or argon plasma coagulation are the preferred methods due to their better safety profile. Intrarectal formalin seems to be effective, but possibly has a higher rate of complications. For resistant disease, hyperbaric oxygen may be an option.

Background & Aims: Systemic corticosteroid therapy increases risk of postoperative sepsis in Crohn's disease. This study investigates its effect on risk for sepsis in non-operated patients. Methods: A retrospective case-control study was performed in 432 patients with Crohn's disease (the 94% of our database for whom adequate documentation could be retrieved). Two analyses were performed. The first tested the hypothesis that patients with perforating Crohn's disease (n = 86) were more likely to develop intra-abdominal or pelvic abscess (n = 29) if they had received systemic corticosteroids during the previous 3 months. The second analysis, confined to interventions since 1998, tested the hypothesis that corticosteroid therapy was more common during the 3 months before presentation with intra-abdominal or pelvic abscess (n = 12) than during the 3 months after presentation with a relapse of nonperforating disease (n = 24 consecutive patients). In both analyses adjustment was made for any other significant variable. Results: Systemic corticosteroid therapy was associated with an adjusted odds ratio (OR) for intra-abdominal or pelvic abscess of 9.03 (95% confidence interval [CI], 2.40-33.98) in patients with perforating Crohn's disease. Patients receiving prednisolone :20 mg per day had an OR of 2.81 (95% CI, 0.99-7.99) for abscess compared with those receiving a lower dose. In patients with relapsed active disease, corticosteroid therapy was associated with an unadjusted OR of 9.31 (95% CI, 1.03-83.91) for intra-abdominal or pelvic abscess. Neither smoking nor azathloprine usage was associated with increased risk for abscess. Conclusions: Systemic corticosteroid therapy for Crohn's disease is associated with increased risk for intra-abdominal or pelvic abscess.

The incidence of oesophageal adenocarcinoma continues to rise rapidly in the West whereas cancer of the stomach is becoming less common. Most patients present with advanced disease that is not amenable to curative treatment. This review focuses on recent evidence on the endoscopic therapy of oesophago-gastric cancer. Although there are many treatment modalities available, there is a paucity of good quality randomised trial evidence on which to base palliative treatment decisions. Furthermore, although palliation of dysphagia may be improved by expandable metal stents or ablative therapy, there is no evidence that this improves survival and each of these therapies has a high frequency of complications particularly in longterm survivors. Exciting developments have however been reported in the therapy of early stage oesophago-gastric cancer. Endoscopic mucosal resection is particularly promising with high rates of complete removal of early cancer or high grade dysplasia. Long-term follow up of these patients is required because of high rates of metachronous tumour formation and at present there are no randomised trial data comparing endoscopic mucosal resection with conventional surgery.

Goblet cell depletion occurs in various forms of colitis, but its mechanism is unknown. We have investigated two linked hypotheses: (i) that bacterial peptides, such as formyl-methionyl-leucyl-phenylalanine (fMLP), interact with epithelial cells inducing the release of chemokines, including interleukin-8 (IL-8), which in turn leads to the recruitment of neutrophils which release mucin secretagogues; (ii) that fMLP acts directly on epithelial cells to cause mucus secretion. Studies were performed to measure the effects of fMLP on the synthesis and secretion of IL-8 and mucus by the goblet cell differentiated colon cancer cell lines HT29-MTX (methotrexate-conditioned HT29 colonic adenocarcinoma cell line) and LS174T, and to assess the effects of neutrophil-derived secretagogues on goblet cell secretion in these cell lines. fMLP (0.1μM) increased the secretion of IL-8 by 105% (P < 0.0001) in HT29-MTX cells and by 401% (P < 0.0001) in LS174T cells. fMLP also increased the synthesis and secretion of mucins by these cell lines, with maximal effects of 65% above control values for synthesis (P < 0.01) and 73% for secretion (P < 0.01). A dose-related increase (up to 67%; P < 0.01) in mucin secretion was demonstrated in HT29-MTX cells in response to incubation with supernatant from activated neutrophils. This effect was largely (83%; P < 0.02) inhibited by ICI 200,355, a specific inhibitor of neutrophil elastase. In conclusion, the bacterial peptide fMLP and neutrophil elastase are both potent mucus secretagogues for colon epithelial cells. fMLP also elicits release of the potent neutrophil chemoattractant IL-8 from colon epithelial cells. These findings support the hypothesis that the mucosal inflammation and mucus depletion seen in ulcerative colitis could result from interaction between bacterial peptides and the mucosa.