N Arebi

Medium‐term results of oral tacrolimus treatment in refractory inflammatory bowel disease

Background This study aimed to evaluate the efficacy of oral tacrolimus in patients with inflammatory bowel disease (IBD) refractory to conventional therapy, including azathioprine, 6‐mercaptopurine, and infliximab. Methods Retrospective review of all patients with IBD treated with oral tacrolimus was undertaken. Tacrolimus was administered at an initial dose of 0.05 mg/kg twice daily, aiming for serum trough levels of 5–10 ng/mL. We evaluated clinical response, a retrospective estimated Crohns disease activity index (CDAI) for Crohns disease (CD), modified Truelove‐Witts index for ulcerative colitis (UC), and modified pouch disease activity index (mPDAI) for pouchitis. Patients had been monitored clinically for benefit and side effects and by whole blood tacrolimus level approximately every 4 weeks for the duration of treatment. Clinical remission was defined as an estimated CDAI <150 (CD), an inactive disease score on the Truelove‐Witts index (UC), and mPDAI <5 (pouchitis). Results Twelve patients with CD, six with UC, and one with pouchitis, all resistant to previous therapies, were treated for a median of 5 months. After 4 weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a clinical response. There was a median reduction of the estimated CDAI of 108 points (range 35–203; P = 0.002) and stool frequency of three per day at week 4. Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the end of follow‐up. Side effects included temporary elevated creatinine (n = 1), tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four patients discontinued treatment due to side effects. Conclusion Oral tacrolimus is well tolerated and effective in patients with refractory IBD in the short‐ to medium‐term. Further controlled, long‐term evaluation is warranted. (Inflamm Bowel Dis 2007)

Review article: the psychoneuroimmunology of irritable bowel syndrome – an exploration of interactions between psychological, neurological and immunological observations

Backgroundu2002 The pathogenesis of irritable bowel syndrome (IBS) is founded on interactive mechanisms. Disentangling these processes is a prerequisite for the development of effective drug therapy.

Clinical and surgical recurrence of Crohn's disease after ileocolonic resection in a specialist unit.

Background Postoperative clinical and endoscopic recurrence is common in Crohns disease. Aim We aimed to assess postoperative recurrence and management in a cross-sectional patient cohort in one specialist unit, before the introduction of a uniform postoperative preventive strategy. Methods Review of patients who had an ileocolonic resection for Crohns disease between 2002 and 2005 in a secondary and tertiary care specialist centre. Results Ninety-nine patients (42 male; 57 female; mean age, 37 years) with a median disease duration of 10 years, were reviewed. Indications for surgery were obstruction (n=61), failed medical therapy (n=31) and internal fistula(e) (n=7). Thirty patients (30%) were active smokers at the time of resection. Fifty patients (51%) had at least one previous Crohns resection. Clinical and surgical recurrence rates were 28 and 5%, respectively, at 1 year. All five patients had the same indication for their further surgery as for their index operation (four fistulizing or stricturing). Median time to clinical recurrence was 10 months in those with recurrence. Nineteen percent of patients had an ileocolonoscopy at a median of 6 months after surgery, and 60% had been reviewed by a gastroenterologist, after surgery. Clinical recurrence occurred in nine of 28 (32%) without and 19 of 71 with (26%) postoperative medical therapy (P=NS). Conclusion Postoperative recurrence of Crohns disease was high in the short term. The indication for repeat surgery stayed true within patients. Prospective treatment strategies, based on recent trial evidence, are needed to diminish postoperative recurrence.

A mechanistic role for leptin in human dendritic cell migration: differences between ileum and colon in health and Crohn's disease

Dendritic cells (DC) migrate to lymph nodes on expression of C-C motif chemokine receptor 7 (CCR7) and control immune activity. Leptin, an immunomodulatory adipokine, functions via leptin receptors, signaling via the long isoform of receptor, LepRb. Leptin promotes DC maturation and increases CCR7 expression on blood DC. Increased mesenteric fat and leptin occur early in Crohn’s disease (CD), suggesting leptin-mediated change in intestinal CCR7 expression on DC as a pro-inflammatory mechanism. We have demonstrated CCR7 expression and capacity to migrate to its ligand macrophage inflammatory protein 3β in normal human ileal DC but not colonic or blood DC. In CD, functional CCR7 was expressed on DC from all sites. Only DC populations containing CCR7-expressing cells produced LepRb; in vitro exposure to leptin also increased expression of functional CCR7 in intestinal DC in a dose-dependent manner. In conclusion, leptin may regulate DC migration from gut, in homeostatic and inflammatory conditions, providing a link between mesenteric obesity and inflammation.

Predictive value and clinical significance of myenteric plexitis in Crohn's disease

Background: Recurrence of Crohns disease (CD) after ileal or colonic resection is common. Myenteric plexitis in the proximal resection margin of an ileocolonic CD resection specimen may indicate ongoing pathology that relates to disease recurrence. We assessed risk factors for myenteric plexitis, the effect of plexitis on clinical recurrence, and whether preoperative medical therapies affect the intensity of plexitis. Methods: Ileocolonic resection specimens from 99 patients with CD were histologically scored for the presence and severity of plexitis. Myenteric plexitis was correlated with immunosuppressive therapy before index surgery. Univariate and multivariate analyses were performed to identify predictive factors for plexitis. Results: Myenteric plexitis was present in 43% and 85% of cases in the proximal resection margin and the affected resected segments of CD, respectively. Patients with a previous resection were more likely to have plexitis than those with no previous resection (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.21–10.15, P = 0.02), and those with a greater duration of disease were less likely to have plexitis in the proximal resection margin (OR 0.68, 95% CI 0.48–0.96, P = 0.03). Preoperative immunosuppressive therapy was not associated with a lesser incidence of plexitis. Twelve of 40 (30%) patients with plexitis and 9 of 54 (16%) patients without plexitis in the proximal resection margin subsequently developed clinical recurrence (median 10 months; P = 0.17). Conclusions: Previous resections and shorter disease duration are associated with plexitis in proximal resection margin of CD. The prognostic value of plexitis in postoperative disease recurrence and risk stratification remain to be prospectively established. (Inflamm Bowel Dis 2009)

Systematic review with meta-analysis: endoscopic balloon dilatation for Crohn's disease strictures

Endoscopic balloon dilatation (EBD) is recognised treatment for symptomatic Crohns strictures. Several case series report its efficacy. A systematic analysis for overall efficacy can inform the design of future studies.

Distinct Neurophysiological Profiles In Irritable Bowel Syndrome

The objective of this study was to determine whether cortical evoked potentials (CEPs) can define neurophysiological patterns in irritable bowel syndrome (IBS). In this prospective study of consecutive patients attending secondary and tertiary centers, patients with Rome II-defined IBS underwent rectal sensory and pain threshold (RST and RPT, respectively) testing with electrical stimulation on three separate visits. CEPs were collated for 75% pain thresholds, and anxiety [Spielberger State-Trait Anxiety Inventory (SSTAI)] questionnaires were completed. Subjects were 33 IBS patients (27 female, mean age 40.1 yr) and 21 healthy controls (14 female, mean age 31.4 yr). At visit 3, RPT was significantly lower [mean (95% CI)] in IBS patients than in control subjects: 58.2 mA (48.0-68.5) vs. 79.5 mA (69.3-89.6) (P < 0.01). No significant differences were observed in CEP latencies and amplitudes between visits 1, 2, and 3 within each group, except P2 latency for controls (P = 0.04) and N2 latency (P = 0.04) and N2 amplitude (P = 0.02) for IBS patients. Group comparisons showed significant differences in 3-day mean RPT, CEP amplitudes, and CEP latencies between IBS patients and controls. RPT <50 mA and P1 latency >106 ms were identified four IBS subgroups: 24% were hypersensitive, 12% were hypervigilant, 15% were hyposensitive, and 49% exhibited normal P1 latency and pain threshold. CEPs are reliable and reproducible measures of early sensory processing. Identification of four IBS neurophysiological patterns highlights its heterogeneous nature. These findings mark the first step toward personalized medicine in IBS, whereby therapy may be directed at the underlying physiological process.

PWE-262 Patients in england with inflammatory bowel disease (IBD) who develop colorectal cancer (CRC) have shortened survival when compared with patients with sporadic CRC

Introduction Ulcerative Colitis (UC) and Crohn’s Disease (CD) are both implicated as risk factors for the development of colorectal cancer (CRC). It is unclear if this patient group has a poor survival after diagnosis. The aim of this study is to determine survival in Inflammatory Bowel Disease (IBD) associated CRC compared with sporadic CRC. Method Patients with a diagnosis of both CRC and IBD were identified from a national administrative dataset (Hospital Episode Statistics – HES). Multivariable cox proportional hazards regression analyses (adjusting for gender, age, medical comorbidity, mode of admission, operation type, chemotherapy) were used to determine survival differences. Results A total of 286,591 patients underwent surgery for CRC in England, between 1997–2012: 0.5% (n = 1,546) had UC and 0.3% (n = 776) had CD. Patients with IBD were diagnosed with CRC at a significantly younger age compared with sporadic patients (UC median age 64, CD median age 63, sporadic median age 71, p < 0.001). Long-term survival in patients with IBD was poor compared with sporadic CRC patients (HR 1.19, CI 1.12–1.26, p < 0.001). On sub-group analysis patients with UC had a 12% reduction in their survival (HR 1.12, CI 1.04–1.20, p = 0.003), whereas those with CD had a 32% reduction (HR 1.32, CI 1.20–1.45, p= <0.01). This difference in survival persisted even when adjusting for immediate post-operative mortality. Conclusion IBD associated CRC develops at a younger age than sporadic CRC with poorer long-term survival, particularly for patients with CD. The reasons for shortened survival amongst IBD patients who develop CRC are unclear. Disclosure of interest None Declared.

PTH-063 Different colectomy rates for ulcerative colitis across ethnic groups in england

Introduction Previous epidemiological studies suggest a higher rate of pan-colonic disease in South Asians (SA) compared with Caucasians. There is limited data on disease severity across ethnic groups. Refractory disease and development of dysplasia indicate aggressive disease and are both indications for colectomy. The aim of the study was to compare the risk of colectomy for ulcerative colitis (UC) in SA migrants to Caucasians. Method Patients with UC were identified from a national administrative dataset (Hospital Episode Statistics – HES) between 1997–2012 according to ICD-10 diagnosis code K51 for UC. From the cases coded for ethnicity, colectomy cases were identified according to the Office of Population Censuses and Surveys (OPCS) codes. The colectomy rate for each ethnic group was calculated as the proportion of patients who underwent colectomy from the total UC cases for that group. The median age at time of colectomy was calculated for each ethnic group. Chi-squared testing was used to determine significant differences in colectomy rate and Kruskal-Wallis test to ascertain differences in age at colectomy between ethnic groups. Results Of 212,430 UC cases, 74,988 (35.3%) were coded for ethnicity. Of these cases most were White Europeans (Caucasians) 69,208/74,988 (92.3%). The SA group consisted of: 1,954/74,988 (2.6%) Indian, 832/74,988 (1.1%) Pakistani and 129/74,988 (0.2%) Bangladeshi (Table 1). Indians had a significantly higher colectomy rate than White Europeans (10.8% vs 7.4%, p < 0.001). In contrast Pakistanis had a similar (7.0%) and Bangladeshis a significantly lower (4.7%) colectomy rate than the White European group. (7.4%, p < 0.001). SAs undergoing colectomy were significantly younger than White Europeans for each ethnic group (median age; Bangladeshis - 29 years, Pakistanis - 37 years and Indians – 41 years, compared with White Europeans – 49 years, p < 0.001).Abstract PTH-063 Table 1 Colectomy rate in UC patients by ethnicity Ethnicity White Europeans Indian Pakistani Bangladeshi No. of colectomies 5150 211 58 6 Total no. of UC cases 69208 1954 832 129 Colectomy rate (%) 7.4 10.8 7.0 4.7 Conclusion The colectomy rate is higher in Indians compared to White Europeans. Across SA ethnic groups there are differences in colectomy rate. All SA groups required a colectomy for UC at a younger age than White Europeans. These findings suggest a more aggressive phenotype in SAs and should be validated with a prospectively recruited ethnic cohort. This will also allow examination of contributing factors. Disclosure of interest None Declared.

PWE-259 Colorectal cancer (CRC) patients with inflammatory bowel disease (IBD) are at increased risk of poor outcomes post surgery in england

Introduction Colorectal cancer (CRC) patients with Ulcerative Colitis (UC) and Crohn’s Disease (CD) can be challenging to manage in the perioperative period. The aim of this study is to examine differences between Inflammatory Bowel Disease (IBD) and sporadic CRC patients in terms of the emergency admission rates, length of stay and post operative complications. Method A national study was carried out using the Hospital Episode Statistics (HES) database between the years of 1997 to 2012. Multivariable binary logistic regression was undertaken to determine whether IBD was independently associated with the development of a postoperative complication. Results During the study time period, 286,591 patient underwent colorectal cancer resection, 0.8% of which (n = 2,322) had IBD. A greater proportion of IBD patients underwent a colorectal cancer resection as an emergency than sporadic patients (UC 25.1%, CD 34.7% and sporadic 24.3%, p < 0.001). IBD patients had a significantly prolonged length of stay after elective surgery for CRC (median number of days length of stay 10 vs. 7, p = 0.001). The overall rate of serious medical complication such as myocardial infarction, stroke, pulmonary embolism was 7.8%, the overall rate of 30-day re-operation was 4.2% (n = 11,987) with a further 0.6% (n = 1,633) requiring radiological re-intervention. A diagnosis of IBD (adjusted for age, gender, comorbidity, mode of admission and type of operation) was an independent predictor of 30-day re-operation (OR 1.32, CI 1.12–1.56, p = 0.001). Conclusion IBD patients, particularly Crohn’s patients commonly have their colorectal cancer resected in an emergency setting. IBD patients are more likely to require 30-day re-intervention, irrespective of other factors. A multi-disciplinary team approach incorporating surgeons, gastroenterologists, anaesthetists and radiologists is essential in the management of these complex patients in the peri-operative period Disclosure of interest None Declared.