INTRODUCTION:Anti-TNF therapy is recommended as treatment for patients with Crohn´s perianal fistulas. However, a significant proportion of patients have a sub-optimal response to anti-TNF therapy. Higher serum levels of anti-TNF agents have been associated with improved outcomes in perianal Crohn's disease. Currently, it is unknown whether anti-TNF agent levels can be detected in tissue from fistula tracts themselves and whether this is associated with response.AIMS AND METHODS:We undertook a pilot study to measure fistula tissue levels of anti-TNF medication (infliximab and adalimumab). We used a previously validated targeted proteomic technique, employing ultraperformance liquid chromatography-mass spectrometry, to detect/quantify anti-TNF drugs. Biopsies were obtained from fistula tracts of patients with Crohn's disease on maintenance treatment; with idiopathic (cryptoglandular) fistula tissues used as negative controls as well as positive controls (by spiking the latter tissues with anti-TNF drugs).RESULTS:Tissue was sampled from the fistula tracts of seven patients with Crohn's perianal disease (five patients were on adalimumab and two patients were on infliximab). The anti-TNF drugs, infliximab and adalimumab, were not detected in fistula samples from any of the Crohn's patients despite detection in 'spiked' positive control samples.CONCLUSION:Absence of detection of the anti-TNF drugs in fistula tissue raises the question on the role of tissue penetrance of anti-TNF drugs in response to therapy. Further work is required in a larger number of patients to validate the findings observed and investigate if any correlation exists between tissue and serum levels of anti-TNF and clinical outcome.SUMMARY:Predicting response in Crohn's fistula patients on biologic therapy is difficult with no reliable biomarkers. This pilot study uses targeted proteomics to investigate the potential role of tissue drug levels in acting as a biomarker of treatment response.

Closure of an abdominal stoma, a common elective operation, is associated with frequent complications; one of the commonest and impactful is incisional hernia formation. We aimed to investigate whether biological mesh (collagen tissue matrix) can safely reduce the incidence of incisional hernias at the stoma closure site.In this randomised controlled trial (ROCSS) done in 37 hospitals across three European countries (35 UK, one Denmark, one Netherlands), patients aged 18 years or older undergoing elective ileostomy or colostomy closure were randomly assigned using a computer-based algorithm in a 1:1 ratio to either biological mesh reinforcement or closure with sutures alone (control). Training in the novel technique was standardised across hospitals. Patients and outcome assessors were masked to treatment allocation. The primary outcome measure was occurrence of clinically detectable hernia 2 years after randomisation (intention to treat). A sample size of 790 patients was required to identify a 40% reduction (25% to 15%), with 90% power (15% drop-out rate). This study is registered with ClinicalTrials.gov, NCT02238964.Between Nov 28, 2012, and Nov 11, 2015, of 1286 screened patients, 790 were randomly assigned. 394 (50%) patients were randomly assigned to mesh closure and 396 (50%) to standard closure. In the mesh group, 373 (95%) of 394 patients successfully received mesh and in the control group, three patients received mesh. The clinically detectable hernia rate, the primary outcome, at 2 years was 12% (39 of 323) in the mesh group and 20% (64 of 327) in the control group (adjusted relative risk [RR] 0·62, 95% CI 0·43-0·90; p=0·012). In 455 patients for whom 1 year postoperative CT scans were available, there was a lower radiologically defined hernia rate in mesh versus control groups (20 [9%] of 229 vs 47 [21%] of 226, adjusted RR 0·42, 95% CI 0·26-0·69; p<0·001). There was also a reduction in symptomatic hernia (16%, 52 of 329 vs 19%, 64 of 331; adjusted relative risk 0·83, 0·60-1·16; p=0·29) and surgical reintervention (12%, 42 of 344 vs 16%, 54 of 346: adjusted relative risk 0·78, 0·54-1·13; p=0·19) at 2 years, but this result did not reach statistical significance. No significant differences were seen in wound infection rate, seroma rate, quality of life, pain scores, or serious adverse events.Reinforcement of the abdominal wall with a biological mesh at the time of stoma closure reduced clinically detectable incisional hernia within 24 months of surgery and with an acceptable safety profile. The results of this study support the use of biological mesh in stoma closure site reinforcement to reduce the early formation of incisional hernias.National Institute for Health Research Research for Patient Benefit and Allergan.

INTRODUCTION:Few studies have investigated perianal fistula etiopathogenesis, and although the cryptoglandular theory is widely accepted in idiopathic cases, in Crohn's disease, it is thought to involve the interplay between microbiological, immunological and genetic factors. A pilot study was conducted to assess for metabolic variations in Crohn's perianal fistula tissue that might differ from that of idiopathic (cryptoglandular) perianal fistula tissue as a comparator. The goal was to identify any potential biomarkers of disease, which may improve the understanding of pathogenesis.AIMS AND METHODS:Fistula tract biopsies were obtained from 30 patients with idiopathic perianal fistula and 20 patients with Crohn's anal fistula. Two different assays were used in an ultra-high-performance liquid chromatography system coupled with a mass spectrometric detector to achieve broad metabolome coverage. Univariate and multivariate statistical data analyses were used to identify differentiating metabolic features corresponding to the perianal fistula phenotype (i.e. Crohn's disease vs. idiopathic).RESULTS:Significant orthogonal partial least squares discriminant analysis predictive models (validated with cross-validated-analysis of variance P value <0.05) differentiated metabolites from tissue samples from Crohn's vs. idiopathic anal fistula patients using both metabolic profiling platforms. A total of 41 metabolites were identified, suggesting alterations in pathways, including amino acid, carnitine and lipid metabolism.CONCLUSION:Metabonomics may reveal biomarkers of Crohn's perianal fistula. Further work in larger numbers is required to validate the findings of these studies as well as cross-correlation with microbiome work to better understand the impact of host-gut/environment interactions in the pathophysiology of Crohn's and idiopathic perianal fistulas and identify novel therapeutic targets.

Objective Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn’s disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. Design Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback from their panel (in the second round) and all participants (in the third round) to allow refinement of their scores. Results A total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study. The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion). Conclusion A fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care.

Background: Perianal Crohn’s fistula and their response to anti-tumour necrosis factor (TNF) therapies are best assessed with magnetic resonance imaging (MRI), but radiologist reporting is subjective and variable. This study investigates whether segmentation software could provide precise and reproducible objective measurements of fistula volume. Methods: Retrospective analysis of patients with perianal Crohn’s fistula at our institution between 2007 and 2013. Pre- and post-biologic MRI scans were used with varying time intervals. A total of two radiologists recorded fistula volumes, mean signal intensity and time taken to measure fistula volumes using validated Open Source segmentation software. A total of three radiologists assessed fistula response to treatment (improved, worse or unchanged) by comparing MRI scans. Results: A total of 18 cases were reviewed for this pilot study. Inter-observer variability was very good for volume and mean signal intensity; intra-class correlation (ICC) 0.95 [95% confidence interval (CI) 0.91–0.98] and 0.95 (95% CI 0.90–0.97) respectively. Intra-observer variability was very good for volume and mean signal intensity; ICC 0.99 (95% CI 0.97–0.99) and 0.98 (95% CI 0.95–0.99) respectively. Average time taken to measure fistula volume was 202 s and 250 s for readers 1 and 2. Agreement between three specialist radiologists was good [kappa 0.69 (95% CI 0.49–0.90)] for the subjective assessment of fistula response. Significant association was found between objective percentage volume change and subjective consensus agreement of response ( p = 0.001). Median volume change for improved, stable or worsening fistula response was −67% [interquartile range (IQR): −78, −47], 0% (IQR: −16, +17), and +487% (IQR: +217, +559) respectively. Conclusion: Quantification of fistula volumes and signal intensities is feasible and reliable, providing an objective measure of perianal Crohn’s fistula and response to treatment.

BACKGROUND AND AIMS:A third of patients with Crohn's disease develop perianal fistulas. These are associated with a significant burden of symptoms and negative impact on quality of life. This study reports the use of video-assisted anal fistula treatment [VAAFT] as a means of symptom improvement; this is a minimally invasive technique to access fistula track, and diagnose/facilitate drainage of deep/complex secondary extensions with cauterization of excess inflammatory tissue.METHODS:Consecutive patients with complex Crohn's fistula undergoing VAAFT for symptomatic Crohn's anal fistula were included. They were identified from a prospectively maintained database, which was interrogated from June 2015 to November 2017. Patients underwent diagnostic fistuloscopy and fulguration of tracts/secondary extensions. Setons were sited/replaced after the procedure to maintain postoperative drainage. The primary endpoint was completion of the 'Measure your medical outcome profile' [MYMOP2] quality of life [QoL] questionnaire at 6 weeks postoperatively. Secondary outcome measures were a decisional regret scale [DRS], postoperative complications and the 30-day re-operation rate.RESULTS:Twenty-five patients underwent the procedure during the study period. In total, 21/25 patients [84%] provided MYMOP2 QoL data demonstrating a statistically significant improvement in both pain and discharge scores. Eighty-one per cent of patients who completed the questionnaire agreed/strongly agreed that the procedure was the right decision and no patient regretted undergoing the procedure. There was one re-operation but otherwise no complications.CONCLUSIONS:This study demonstrates the feasibility, safety and importantly an improvement in patient-reported outcomes in a series of patients undergoing VAAFT for complex Crohn's anal fistula. VAAFT reduces the main symptoms [pain and discharge] in patients with complex refractory anal fistulas.

BACKGROUND: The characteristics of patients who develop a fistula-in-ano after an anorectal abscess are unclear. OBJECTIVE: Our study explored this relationship and patient factors associated with fistula development. DESIGN: International Classification of Diseases, 10th Revision, and Classification of Interventions and Procedures, version 4, codes were used to identify all of the patients with a primary anorectal abscess. Multivariable analysis was used to identify factors predictive of fistula formation. SETTINGS: The study was conducted in a district general hospital. PATIENTS: Patients with anorectal abscess who were admitted to our institution (2004–2015) were included. MAIN OUTCOMES MEASURES: The rate of subsequent fistula formation was measured. RESULTS: A total of 1970 abscess patients were identified; 70.0% (n = 1379) were men, and 7.3% (n = 144) had Crohn’s disease. Fistulas occurred in 16.2% (n = 319) at a median of 7 months (interquartile range, 3–7 mo). Patients with Crohn’s disease were more than twice as likely to develop a fistula than patients without Crohn’s disease (32.6% vs 14.9%; OR = 2.5 (95% CI, 1.7–3.7); p < 0.001). Patients with Crohn’s disease with a fistula were more likely to be women (55.3% vs 34.6%; p = 0.007) and aged <30 years (51.1% vs 24.3%; p< 0.001) versus patients without Crohn’s disease with a fistula. At multivariable analysis of the entire cohort, male sex (OR = 0.7 (95% CI, 0.5–0.9); p = 0.005) and diabetes mellitus (OR = 0.5 (95% CI, 0.3–0.9); p = 0.027) were associated with a reduced likelihood of developing a fistula after abscess formation. LIMITATIONS: The study was limited by its single-center scope, retrospective analysis, and lack of a standardized definition for Crohn’s disease. CONCLUSIONS: Abscesses are more common in men, but progression to fistula is more likely in women. The rate of fistula progression in Crohn’s disease is twice that in patients without Crohn’s disease. Identification of patients at risk may help delineate those who will benefit from a more conservative surgical approach, enhanced follow-up, or investigation after abscess drainage. See Video Abstract at http://links.lww.com/DCR/A798.

Background Perianal fistulising Crohn’s disease (PFCD) affects a third of Crohn’s disease patients and represents a disabling phenotype with poor outcome. The anti-tumour necrosis factor alpha (TNF) therapies have been shown to maintain clinical remission in a third of patients after 1 year of treatment. Maintenance therapy with systematic administration schedules confers greatest benefit, but exposes patients to risks/side effects of continued systemic use and led to consideration of local drug delivery (first described in 2000). In this review, we analyse all published articles on local anti-TNF therapy in the treatment of PFCD. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to systematically search Medline and Embase using the medical subject headings ‘fistula’, ‘anus’, ‘Crohn disease’, ‘infliximab’ and ‘adalimumab’. This was combined with free text searches, e.g. ‘local injection’ and ‘Crohn’s perianal disease’. Studies/abstracts describing local injection treatment with anti-TNF were included in this review. Results Six pilot studies including a total of 92 patients were included in this review. Outcomes reported were mostly clinical and included ‘complete/partial response’ to therapy and short-term results varied between 40 and 100%. There were no significant adverse events and the local injections were well tolerated. Conclusions There is paucity of data assessing this treatment modality. Local anti-TNF therapy appears safe, but outcome reporting is heterogeneous, subjective and long-term data are unavailable. Our review suggests a potential role may be in those in whom systemic treatment is contraindicated and calls for standardised reporting of outcomes in this field to enable better data interpretation.

only Painful initially, patient preference No cost Digitation Pilot RCTs 28 Potential risk of premature closure No cost Open wound (fig 4⇓) RCT = randomised controlled trial. For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe BMJ 2017;356:j475 doi: 10.1136/bmj.j475 (Published 2017 February 21) Page 4 of 6

Background & Aims: Most knowledge about gastrointestinal (GI)-tract dendritic cells (DC) relies on murine studies where CD103+ DC specialize in generating immune tolerance with the functionality of CD11b+/− subsets being unclear. Information about human GI-DC is scarce, especially regarding regional specifications. Here, we characterized human DC properties throughout the human colon. Methods: Paired proximal (right/ascending) and distal (left/descending) human colonic biopsies from 95 healthy subjects were taken; DC were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing. Results: Colonic DC identified were myeloid (mDC, CD11c+CD123−) and further divided based on CD103 and SIRPα (human analog of murine CD11b) expression. CD103-SIRPα+ DC were the major population and with CD103+SIRPα+ DC were CD1c+ILT3+CCR2+ (although CCR2 was not expressed on all CD103+SIRPα+ DC). CD103+SIRPα- DC constituted a minor subset that were CD141+ILT3−CCR2−. Proximal colon samples had higher total DC counts and fewer CD103+SIRPα+ cells. Proximal colon DC were more mature than distal DC with higher stimulatory capacity for CD4+CD45RA+ T-cells. However, DC and DC-invoked T-cell expression of mucosal homing markers (β7, CCR9) was lower for proximal DC. CCR2 was expressed on circulating CD1c+, but not CD141+ mDC, and mediated DC recruitment by colonic culture supernatants in transwell assays. Proximal colon DC produced higher levels of cytokines. Mucosal microbiota profiling showed a lower microbiota load in the proximal colon, but with no differences in microbiota composition between compartments. Conclusions: Proximal colonic DC subsets differ from those in distal colon and are more mature. Targeted immunotherapy using DC in T-cell mediated GI tract inflammation may therefore need to reflect this immune compartmentalization. Keywords: CCR2, Dendritic Cells, Distal Colon, Human Gastrointestinal Tract, Proximal Colon, Microbiota

Yassin, Nuha A. M.B.Ch.B., M.R.C.S., M.Sc., Ph.D.; Dardanov, Dragomir M.D., Ph.D.; Phillips, Robin K. S. M.S., F.R.C.S. Author Information

BACKGROUND & AIMS: Most knowledge about gastrointestinal (GO-tract dendritic cells (DC) relies on murine studies where CD103(+) DC specialize in generating immune tolerance with the functionality of CD11B(+/-) subsets being unclear. Information about human GI-DC is scarce, especially regarding regional specifications. Here, we characterized human DC properties throughout the human colon.METHODS: Paired proximal (right/ascending) and distal (left/descending) human colonic biopsies from 95 healthy subjects were taken; DC were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing.RESULTS: Colonic DC identified were myeloid (mDC, CD11c(+)CD123(-) ) and further divided based on CD103 and SIRP alpha (human analog of murine CD11b) expression. CD103 SIRP alpha(+) DC were the major population and with CD103(+) SIRP alpha(+) DC were CD1c(+) ILT3(+)CCR2(+) (although CCR2 was not expressed on all CD103(+) SIRP alpha(+) DC). CD103(+)SIRP alpha(-) DC constituted a minor subset that were CD141(+)ILT3(-)CCR2(-). Proximal colon samples had higher total DC counts and fewer CD103(+)SIRP alpha(+) cells. Proximal colon DC were more mature than distal DC with higher stimulatory capacity for CD4(+)CD45RA(+) T-cells. However, DC and DC-invoked T-cell expression of mucosal homing markers (beta 7, CCR9) was lower for proximal DC. CCR2 was expressed on circulating CD1c(+), but not CD141(+) mDC, and mediated DC recruitment by colonic culture supernatants in transwell assays. Proximal colon DC produced higher levels of cytokines. Mucosal microbiota profiling showed a lower microbiota load in the proximal colon, but with no differences in microbiota composition between compartments.CONCLUSIONS: Proximal colonic DC subsets differ from those in distal colon and are more mature. Targeted immunotherapy using DC in T-cell mediated GI tract inflammation may therefore need to reflect this immune compartmentalization.

1111 Diseases of the Colon & ReCtum Volume 58: 11 (2015) When evaluating anorectal sepsis, we depend on adequate physical imaging alongside an image in our mind’s eye of anorectal anatomy. imaging is frequently used as an adjunct to clinical examination and examination under anesthesia, aiding understanding and hence management. the surgeon seeks to understand the anal canal and fistula anatomy, identify secondary tracts and high extensions, and discriminate between granulation tissue and abscesses/trapped pus. ortega et al have supplied interesting evidence based on an extensive experience of evaluating anorectal sepsis using Ct scanning. one central reason is to help guide the surgeon in the important and difficult decision regarding whether to drain sepsis directly into the rectum or via the ischiorectal fossa. the image in their minds’ eye has the deep postanal space as central. in the united states, hanley proposed the deep postanal space as central to the management of some complex fistulas. this teaching has been at the core of the article by ortega et al but in our view is based on an enigma. the boundaries of this hypothetical space are the levator ani above, the external anal sphincter anteriorly, and the anococcygeal ligament below. from a european perspective, a ligament with an origin from 1 bone (here the coccyx) would by definition have an insertion into another. We europeans do not have a bone in our anuses, but cannot speak with authority about north americans. We supply both cadaveric and magnetic resonance evidence that there is no structure inferiorly that might serve as a boundary to an anatomically definable deep postanal space. We believe the original question to be a riddle (albeit important), the imaging method selected (Ct) a mystery (mRi is so much better), and the deep postanal space itself an enigma (and probably a myth). in our view, such a riddle wrapped in a mystery inside an enigma cannot forecast action. We have attached images to make the following points: 1) Ct does not have the quality of mR, 2) anatomic dissection shows no evidence of an anococcygeal ligament, and 3) matching mRi scanning also fails to demonstrate a ligament or a true deep postanal space.

Introduction Anti-tumor necrosis factor (TNF) therapies are currently being used to treat fistulising perianal Crohn's disease (CD). We evaluated the clinical and radiological outcomes of patients with perianal Crohn's fistulas who have been treated with immunomodulators alone as compared with those treated with anti-TNF therapies. Methods A local database of 270 consecutive patients with CD anal fistulas treated at our institution between 2000 and 2014 was established. Demographic and clinical data were recorded in addtion to radiological reports. Results Ninety patients were in the non-anti-TNF group and 180 were treated with anti-TNF therapy (Infliximab or Adalimumab). Clinical response rates were significantly higher in the anti-TNF group (74% vs 62%, p=0.04). Similarly, radiological response rates were higher in the anti-TNF group (56% vs 28%, p<0.01). Cox Regression analysis demonstrated fistula duration (p=0.01) and biologic therapy (p=<0.01) to be significant at the univariate level. At the multivariate level, patients on anti-TNF therapy had a faster radiological response over a 6-year follow-up period (OR=2.25, CI= 1.14-4.46, p= 0.02). A short duration of CD (less than 5 years) contributes to a faster time to clinical response (OR=1.77, CI=1.03-3.05, p=0.04). Treatment with anti-TNF therapy is an independent predictor of radiological response (OR 3.55, CI 1.59-7.91, p<0.01). Patients with L1 luminal disease are 3 times more likely not to go into clinical remission on both univaraite and multivariate analyses (OR=3.08, CI=1.47-6.46, p=0.01). The duration of CD is also a poor predictor of clinical response to therapy (p<0.01). Conclusion Patients on anti-TNF therapy have improved clinical and radiological response rates compared with patients without. Anti-TNF therapy is a positive predictor of radiological response to therapy.

BACKGROUND AND AIM:Although Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised trial of celecoxib (CXB) versus CXB+diflouromethylornithine (DFMO) to determine the synergistic effect, if any. METHODS:The primary endpoint was % change in adenoma count in a defined field. Secondary endpoints were adenoma burden (weighted by adenoma diameter) and video review of entire colon/rectal segments. Adverse event (AEs) were monitored by National Cancer Institution toxicity criteria. RESULTS:112 subjects were randomised: 60 men and 52 women at a mean age of 38 years. For the 89 patients who had landmark-matched polyp counts available at baseline and 6 months, the mean % change in adenoma count over the 6 months of trial was -13.0% for CXB+DFMO and -1.0% for CXB (p=0.69). Mean % change in adenoma burden was -40% (CXB+DFMO) vs -27% (CXB) (p=0.13). Video-based global polyp change was -0.80 for CXB+DFMO vs -0.33 for CXB (p=0.03). Fatigue was the only significant AE, worse on the CXB arm (p=0.02). CONCLUSIONS:CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma count, the primary endpoint, was seen between the two study arms. No evidence of DFMO-related ototoxicity was seen. There were no adverse cardiovascular outcomes in either trial arm and no significant increase in AEs in the CXB+DFMO arm of the trial. Differences in outcomes between primary and secondary endpoints may relate to sensitivity of the endpoint measures themselves. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov number N01-CN95040.

Introduction: Chemoprevention prevents colorectal polyps in adults with familial adenomatous polyposis (FAP) but its effect on polyposis in children with FAP is not established. This double-blind, 18-center, 13-country, 5-year study evaluated the efficacy and safety of celecoxib versus placebo in the prevention of colorectal polyps in pediatric subjects with FAP. Methods: Subjects aged 10-17 years with <20 polyps >2 mm in size that were completely excised on baseline study colonoscopy were eligible. Patients with >20 polyps >2 mm were excluded. Subjects were randomized at a 1:1 ratio to celecoxib 16 mg per kg per day or placebo, and underwent yearly colonoscopy. The primary endpoint was time-to-treatment failure, defined as time from randomization to the earliest occurrence of ≥20 polyps >2 mm in size at any study colonoscopy or diagnosis of colorectal cancer. Results: The first patient was randomized in 2006 and study was terminated in October 2013 due to lower than expected rate of endpoints. One hundred six subjects (55 celecoxib/51 placebo) with a mean age of 12.6 years and 12.2 years, respectively, were randomized. Treatment duration was 23 months in the celecoxib arm and 25.5 months in the placebo arm; 13% subjects in the celecoxib group and 26% in the placebo group developed >20 polyps >2 mm in size. Among them, median time to progression was 2.1 years in the celecoxib group and 1.1 years in the placebo group, respectively. No subject developed colorectal malignancy. All causality treatment-emergent adverse events (TEAE) were similar between the groups: 40 (76%) subjects in the celecoxib group and 35 (73%) subjects in the placebo group. Treatmentrelated TEAEs was similar: 18 (34%) subjects in the celecoxib group and 15 (31%) subjects in the placebo group. The most common AEs (occurring in >10% of subjects in a group) were abdominal discomfort, abdominal pain, diarrhea, nausea, vomiting, fatigue, seasonal allergy, influenza, nasopharyngitis, upper respiratory tract infection, pain in extremity, headache, cough, and oropharyngeal pain. Conclusion: Pediatric FAP patients randomized to celecoxib were observed to have half the event rate and a delay in progression of adenomas compared to patients in the placebo arm after a median of 2 years of treatment. Due to the premature termination of the study, the impact of the results cannot be certain. High-dose treatment with celecoxib in children with FAP was generally well tolerated and safe. The CHIP study is registered at ClinicalTrials.gov identifier: NCT00585312. Disclosure - Burke, Phillips and Lynch: Research support and Study Steering Committee Members. Berger, Li and Iorga: Pfizer employees. Berger and Li: Pfizer stock options. This research was supported by an industry grant from Pfizer.

Introduction: Familial adenomatous polyposis (FAP) is a rare condition, characterised by the development of multiple adenomatous polyps in the colon and rectum but which also displays a number of extra-colonic manifestations. Undoubtedly, there have been major advances in our understanding and management of FAP. However, despite these advances patients with FAP have a fourfold mortality rate when compared with the general population.Areas covered: The published literature has been critically appraised, focusing on four main areas: genetic aspects of FAP, management of the colorectum, understanding and management of desmoids tumours and the management of duodenal disease in FAP. The progress in these areas that has been made over recent years has then been described, with regard to our scientific understanding as well as clinical management of the condition.Expert opinion: Expert opinion is provided regarding on-going clinical dilemmas. In particular, the expert opinion focuses on clinical management and areas of research that are required, which may directly influence clinical management of this condition, thereby improving the outcome of patients with FAP.

There are many radiological imaging techniques for perianal fistulas; the choice of modality may depend on several factors other than simply diagnostic accuracy. Equipment availability and financial constraints vary between healthcare systems. Inexperienced clinical assessment may miss secondary extensions; the resulting recurrence is expensive and upsetting for patients. Fistulography no longer has a role in fistulas arising from the anus itself, but it may be useful in identifying extra-sphincteric tracts arising from abdominal organs, such as appendix, terminal ileum, and sigmoid colon. CT has a limited role acutely but otherwise there are better methods. In the right hands, Endo-anal ultrasonography is still more accurate than clinical examination alone, but requires considerable skill in interpretation, is operator dependent, and may not be suitable for all patients. magnetic resonance imaging scans are the gold standard for fistula.