SROC curve revealing moderate diagnostic accuracy of PAB for the diagnosis of IBD

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Upper Gastrointestinal Tract Involvement in Crohn's Disease Requiring Anti-TNF Therapy: Clinical CharacteristicsWilliam J. Tremaine, William A. Faubion, Darrell S. Pardi, Lawrence J. Timmons,Sunanda V. Kane, Edward V. Loftus

Crohn's disease of the upper GI tract has been reported to be associated with more severedisease compared to lower GI involvement alone. Aim: To determine the clinical featuresof patients (pts) with Crohn's disease with upper GI tract involvement with severe diseaseas indicated by the need for anti-TNF alpha therapy. Methods: The medical records of ptswith upper GI tract Crohn's disease seen at a tertiary care center between January 1, 1999and December 31, 2009 were reviewed and those treated with an anti-TNF biologic wereincluded. Results: We confirmed 410 patients with Crohn's disease with upper GI tractinvolvement including 33 treated with biologics (infliximab 22; adalimumab 5; multiplebiologics 5; certolizumab pegol 1). There were 21 females (64%). Median age was 33 years(range, 12-62). Five pts had a family history of IBD. Six pts were current smokers at thestart of biologic therapy. Upper GI symptoms were predominant in only 9 pts (28%) and7 of the 9 pts (78%) had symptom relief with biologic treatment. One pt had gastric Crohn'sdisease without distal involvement; 30 pts also had ileal and/or colonic disease and two ptshad perianal disease without ileal or colonic disease. Altogether, sixteen pts (48%) hadperianal disease. Granulomas were identified in 10 pts (30%). Seventeen pts (52%) hadprevious surgery for Crohn's disease. A total of ten pts had a complete clinical response,10 pts had a partial clinical response, and 13 pts had no response. Ten pts (30%) had severeadverse reactions to biologics requiring discontinuation of therapy, including: dermatitis 3;infections 2; delayed hypersensitivity reactions 2; anaphylaxis 1; oral lesions 1; and congestiveheart failure 1. Conclusions: Lower GI symptoms are the usual indications for biologictherapy in pts with UGI tract Crohn's disease. Only one pt had isolated upper GI tractCrohn's disease. Granulomas were found in about a third of patients with UGI Crohn'streated with biologics. Nearly half of patients with upper GI Crohn's disease requiringbiologics had perianal disease. Most patients with symptomatic upper GI Crohn's diseaseimproved with biologic therapy, but more than one out of four pts had severe complicationsfrom therapy.

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Anti-TNF Agents are Changing the Natural History of Crohn's DiseaseYi - Tzu Nancy Fu, Thomas Hong, Hong Qian, Brian Bressler

Background: Anti-TNF agents have been available for treating patients with Crohn's disease(CD) for over a decade. However, it is still unclear whether these agents significantly impactthe natural progression of CD. Aim: We investigated the difference in patient phenotype,time from disease diagnosis to surgery, medication usage and amount of small bowel resectedin patients with CD undergoing their first surgical resection between 1995-2000 and 2005-2010. Methods: We retrospectively evaluated all patients with CD undergoing their firstsurgical resections between 1995-2000 and 2005-2010 at a tertiary care hospital (St. Paul'sHospital, Vancouver, Canada). Patients were identified using ICD 9/10 diagnostic codes andtheir electronic records were reviewed. For statistical analysis, chi-square tests were performedfor categorical variables, and t tests orWilcoxon rank-sumwere used for continuous variables.Results: There were 85 and 114 CD patients who had surgical resection between 1995-2000 and 2005-2010, respectively. Compared to 1995-2000, the 2005-2010 cohort hadmore patients that were male (1995-2000 vs. 2005-2010; 30.6% vs. 54.4%, p=0.001) andon immunosupressants (21.4% vs. 56.1%, p<0.0001), but less on 5-aminosalysilic acid(53.6% vs. 29.8%, p=0.001). Thirty eight patients (33.3%) received anti-TNF agents in thelater cohort, no patient received anti-TNF agents in the earlier cohort. Based on the Montrealclassification, patients requiring surgery had significantly different disease behaviour (B1/B2/B3 38.8%/31.8%/29.4% vs. 12.3%/45.6%/42.1%, p<0.0001) and disease location (L1/L2/L3 32.9%/28.2%/38.8% vs. 26.3%/14.9%/58.8%, p=0.01). Both groups had similarmedian age, time from diagnosis to surgery, amount of small bowel resected, corticosteroiduse, and post-operative complications. Within the 2005-2010 cohort, 38 patients (33.3%)received anti-TNF agents. Compared to patients not on anti-TNF agents, these patients hadsimilar disease behaviour, but significantly different age at diagnosis (No anti-TNF agents

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vs. anti-TNF agents; A1/A2/A3 11.8%/73.7%/14.5% vs. 39.5%/50%/10.5%, p=0.003) anddisease location (L1/L2/L3 27.6%/7.9%/64.5% vs. 23.7%/29%/47.4%, p=0.01). Significantlyshorter median time from diagnosis to surgery was observed in patients not receiving anti-TNF agents (48 vs. 90 months, p=0.02). Interestingly, this was shorter than the 72-monthmedian time for the 1995-2000 cohort; suggesting an overall sicker patient population inthe 2005-2010 cohort. Conclusions: Significantly different patient phenotype and medica-tion usage were observed in the anti-TNF versus pre-anti-TNF era. Patients on anti-TNFagents had longer time from disease diagnosis to their first surgical resection. Anti-TNFagents are changing the natural history of Crohn's disease.

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Treatment of Refractory Crohn's Disease With Allogeneic, Bone Marrow-Derived Adult Mesenchymal Stromal CellsRenate Schmelz, Stefan Brueckner, Jana Babatz, Katja Richter, Nadine Muench, KristinaHoelig, Mathias Krech, Martin Bornhäuser

Objectives: Crohn's disease is characterized as a life-long, chronic inflammatory bowel diseasewith pathologic T-cell response which can occur in every part of the gastrointestinal tract. Animbalance in local mucosal production of pro-inflammatory cytokines over anti-inflammatorycytokines is theorized to cause the well-demarcated, discontinuous, transmural, ulcerativelesions characteristic of the disease. Some patients present as treatment-refractory Crohn'sdisease with poor clinical outcome. Mesenchymal stromal cells (MSC) can affect an adaptiveimmune response by exerting their immunoregulative effects through direct interaction withT-cells and blocking of TNF-alpha. These immunoregulatory effects mainly occur in alocalized tissue environment and have limited systemic consequences. Methods: During 06/2009 until 04/2011 seven patients (n= 4 female) with refractory Crohn's disease (n=4:ileostoma with peristomal ulcer and/or fistula, n=1: intrapyloric ulcer, n= 1: inflammatorystenosis of the rectum, n=1: CDAI 308) were treated with MSCs. Bone-marrow derivedMSCs from unrelated HLA disparate donors were expanded in platelet lysate containingmedium and characterized by their morphological, phenotypical and functional properties.An intravenous application of MSCs ranging from 0.94*10^6 cells/kg to 2.01*10^6 cells/kg respectively was performed at day 1 and 4. Results: Two patients (29%) showed acomplete response of their fistulas and/ or ulcers in the para-ileostomal region. One patienthad partial response with complete closure of the peristomal ulcers, but no effect on hisenterocutaneous fistula. Four patients represented without any significant treatment response.One male showed an allergic reaction according to DMSO during the first application ofMSCs, the second application was tolerated very well. No other side effects occurred.Conclusion: MSCs should be considered as a therapeutic option in patients who have failedto respond to standard treatment. Response rate in our case series was 29%. Particularlypatients with peristomal problems e.g. fistulas und ulcers seem to profit. MSC-based treatmentis well tolerated and a potent therapy which should be confirmed in controlled studies. Stillit remains very interesting if higher doses of MSCs could achieve increased response rates.

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Disparity in Clinical Care for Patients With Inflammatory Bowel DiseaseBetween Specialists and Non-SpecialistsTomoko Hirakawa, Jun Kato, Sakuma Takahashi, Hideyuki Suzuki, Mitsuhiro Akita,Shunsuke Saito, Eisuke Kaji, Sakiko Hiraoka, Hiroyuki Okada, Kazuhide Yamamoto

BACKGROUND: Although inflammatory bowel disease (IBD) patients have been increasingand new therapeutic options for IBD have developed, doctors who specialize in IBD arerelatively few. Patients treated by a non-specialist of IBD may not receive appropriatetreatment. The aim of this study is to clarify importance of expertise in IBD by comparingdisease and medication status between IBD patients treated by an IBD specialist and thosetreated by an IBD non-specialist. METHODS: Medical charts of ambulating IBD patients intwo hospitals at the same time point (November 2010) were examined. All patients in onehospital were treated by one of IBD specialists, while in the other, patients were treated byone of gastroenterologists of non-specialist of IBD. RESULTS: The numbers of IBD patientswere 255 (hospital with specialists) and 74 (hospital without specialists), respectively. Extens-ive colitis, left-sided colitis, and proctitis were nearly evenly distributed in ulcerative colitis(UC) patients of the hospital with specialists, while approximately two thirds of UC patientsin the hospital without specialists were extensive colitis (p = 0.0007). Disease activity wasnot well-controlled in the patients of the hospital without specialists compared to in thepatients of the hospital with specialists (remission or mild activity; UC: 93% vs. 77%, p =0.0006 and Crohn's disease (CD): 85% vs. 62%, p = 0.012, respectively). 5-ASA agentswere not sufficiently utilized for patients in the hospital without specialists. For example,the proportion of patients using salazosulfapyridine was significantly higher in UC patientsof the hospital with specialists than in UC patients of the hospital without specialists (30%vs. 7%, p = 0.0022). On the other hand, the proportion of UC patients who receivedinsufficient dose of mesalazine (Pentasa < 3 g/day or Asacol < 3.6 g/day) was significantlyhigher in the hospital without specialsits (47% vs. 15%, p < .0001). Moreover, topicaltherapy was less frequently used for UC patients in the hospital without specialists (2% vs.17%, p = 0.013). In the hospital without specialists, significantly more patients receivedlong-term (more than 6months) oral corticosteroids (UC: 23% vs. 5%, p < .0001, CD: 23% vs.4%, p = 0.012, respectively), while significantly fewer patients received immunomodulators(azathioprine or mercaptopurine) (UC + CD; 14% vs. 44%, p < .0001). Biologics use inCD was more familiar in the hospital with specialists (46% vs. 15%, p = 0.0083). CONCLU-SION: IBD patients of the hospital without specialists were not well-controlled and werenot prescribed therapeutic drugs appropriately. Fostering and placement of the specialistsof IBD is an urgent problem for disseminating appropriate IBD treatment.

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