Characterization of mucosal vs transmural process in inflammatory bowel disease using optical...

before the first and after the last CPT. Sigmoidoscopy was performedwithout preparation and biopsy specimens were taken 20 cm from the analverge and then fixed by NaCacodylate in Gluteraldehyde. Detailed analysisof MC & epithelial mitochondria was performed by EM. MC were clas-sified as “activated” if piecemeal degranulation, granular halo or anaphy-lactic degranulation was observed. MC were regarded as “degranulated” ifthey only had evidence of anaphylactic degranulation. The epithelial mi-tochondria were also evaluated for structural damage. Two independentblinded observers interpreted the result and both observers reevaluateddissimilar reports.Results: MC showed activation and degranulation after CPT (P�0.002 &0.005, respectively). Stratifying for IBD, MC were active in 20% ofcontrols and 21% of IBD prior to CPT. After CPT, however, this numberrose to 66% and 78% in the corresponding groups. Only in subjects withIBD CPT–induced MC activation and degranulation reached statisticalsignificance (P�0.016 & 0.002, respectively). Furthermore, epithelial mi-tochondria, showed a significant structural damage (swelling & loss ofcrista) after CPT, P�0.04.Conclusions:

1– Our study suggests that intestinal MC act as an end effector of BGAand will be both activated and degranulated after physiological stress.

2– Intestinal MC of IBD patients are more activated and degranulatedwith physiological stress as compared to healthy controls.

3– Physiological stress resulted in significant structural damage to in-testinal epithelial mitochondria.

These may contribute to the stress–induced leaky gut and /or initiation ofinflammatory process and flare–up.

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CHARACTERIZATION OF MUCOSAL VS TRANSMURALPROCESS IN INFLAMMATORY BOWEL DISEASE USINGOPTICAL COHERENCE TOMOGRAPHY (OCT) – AN EX VIVOSTUDYB. Shen, M.D., G. Zuccaro, M.D.*, T. Gramlich, M.D., N. Gladkova,M.D., D. Conwell, M.D., C. Delaney, M.D., F. Feldchstein, Ph.D., M.Kareta, B.S., J. Dumot, D.O., J. Vargo, M.D., J. Connor, M.S., B.Lashner, M.D., M. Bambrick, R.N., C. Bevins, M.D. and V. Fazio, M.D.Digestive Disease Center, Cleveland Clinic, Cleveland, OH; AnatomicPathology, Cleveland Clinic, Cleveland, OH and Nizhny NovgorodMedical Academy, Nzhny Novgorod, Russian Federation.

Purpose: Distinguishing Crohn colitis from ulcerative colitis (UC) isimportant, but sometime difficult. Transmural inflammation, a hallmark forCrohn disease (CD), can not be readily assessed by endoscopy withmucosal biopsy. OCT provides a cross–sectional image deep enough toassess all layers of the colon wall with a resolution higher than high–frequency EUS. It utilizes a small–caliber probe suitable for both ex vivoand in vivo studies. Aim: To characterize OCT image patterns in UC & CDin correlation with histology.Methods: 233 ex vivo OCT images were obtained from surgically resectedcolon specimens of 5 UC pts, 11 CD pts (involving colon & ileum), and 6invasive colon cancer pts (controls for nl colon & transmural process). Thediseased and non–diseased tissues imaged were resected for histology andevaluated by a blinded GI pathologist. 5 gastroenterologists blinded tomacroscopic and histologic findings assessed each OCT image indepen-dently to determine whether the layer structure of colon wall was preservedor disrupted by mucosal, submucosal, and transmural disease. Inter–ob-server agreement was assessed.Results: On histology, UC involved the mucosa w/ or w/o submucosa,while CD could involve all layers of the colon wall. On OCT, the layerstructure of the colon wall was often intact in the mucosal disease, but wasdisrupted in transmural disease seen only in CD. The sensitivity for trans-mural CD was 88%. The overall kappa coefficient for interpreting the OCTimage was 0.53 (95% CI�0.47, 0.59).Conclusions: 1) Histologic transmural disease was seen only in CD and notin UC; 2) Transmural disease was characterized by disruption of the layer

structure of colon wall on OCT, which could serve a sensitive and objectivemarker for the diagnosis of CD with a good inter–observer agreement.

Histopathology Optical Coherence Tomography

Levelinvolved on

histology

UlcerativeColitis

(64 images)Crohn Disease(121 Images)

DisruptedLayers–

Probability(95% CI)

Intact Layers–Probability(95% CI)

Inter–observer

Agreement

None 5 (8%) 19 (16%) 0.02 (0.01, 0.04) 0.98 (0.96, 0.99) 0.92

Mucosa 37 (58%) 46 (38%) 0.10 (0.06, 0.16) 0.90 (0.84, 0.94) 0.68

Mucosa and

submucosa

22 (34%) 15 (12%) 0.43 (0.30, 0.56) 0.57 (0.44, 0.70) 0.79

Transmural 0 41 (34%) 0.88 (0.83, 0.92) 0.12 (0.08, 0.17) 0.77

*Normal tissue (adjacent to diseased area) imaged then resected

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GRANULOCYTE ADSORPTION APHERESIS AS AN ADJUNCTTO CONVENTIONAL THERAPY FOR PATIENTS WITHCORTICOSTEROID DEPENDENT ULCERATIVE COLITISMichiko Nakano, M.D., Kazunari Kanke, M.D., Keiichi Tominaga, M.D.,Yoshihiro Watanabe, M.D., Yasunaga Suzuki, M.D., Motoo Ishida, M.D.,Hironori Masuyama, M.D., Hideyuki Hiraishi, M.D., Akira Terano,M.D.*, Abby R. Saniabadi, Ph.D. and Chikako Shima, M.Sc.Department of Gastroenterology, Dokkyo University School of Medicine,Mibu, Tochigi, Japan and Department of Science, JapanImmunoresearch Laboratories, Takasaki, Gunma, Japan.

Purpose: Several recent studies have reported a strong association betweenfaecal calprotectin level (a neutrophil protein), the severity of intestinalinflammation and ulcerative colitis (UC) relapse, implying that, granulo-cytes infiltrate the mucosa and when their numbers reaches a criticaldensity, UC relapse occurs. Additionally, corticosteroids (CS) are known topromote neutrophil survival. We thought that reduction of granulocytes byadsorption apheresis (GCAP) might reduce inflammation and allow taper-ing of CS dose which otherwise could provoke a relapse.Methods: Patients were 25 adults, 13 males and 12 females, mean age 33.1yr, all with an active flare of UC and a history of frequent relapses duringtapering of prednisolone (PSL) dose. GCAP was done with a 335 mLcapacity column filled with cellulose diacetate beads of 2 mm in diameteras adsorptive carriers (Adacolumn). The carriers adsorb granulocytes andmonocytes/macrophages. Each patient received 1 or 2 GCAP sessions/week, up to 10 sessions. The flow rate was 30 mL/minute, one session was60 to 90 minutes. Efficacy was assessed by using Seo’s activity index (AI)(Seo et al., Am J Gastroenterol 1992; 87: 971–6)). No new medication wasadministered, but all patients were on PSL at entry to GCAP.Results: At entry, patients had a mean AI of 195.3. Efficacy was assessedwithin 14 days of the last GCAP session. Patients who had an AI equal orless than 150 were assessed as markedly improved. Of 25 patients, 15(60%) responded to the therapy and subsequently discontinued PSL.Eleven patients (44%) had a dramatically reduced mean AI, 111.7. Thetreatment was well tolerated, patient compliance was 100% and no severeside effects were observed.Conclusions: Patients with CS dependent UC should respond to GCAPtherapy and may become steroid free. The efficacy of GCAP appears to beattributable to an effect on the level of inflammatory cytokine producingleukocytes, but other cellular or immunological effects of GCAP can not beruled out. Accordingly, GCAP might be an effective adjunct to conven-tional therapy with potential to spare CS.

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CLINICAL CHARACTERISTICS OF FAMILIAL VS. SPORADICCROHN’S DISEASE USING THE VIENNA CLASSIFICATIONBurton I. Korelitz, M.D., M.A.C.G.*, Spencer D. Dorn, M.D., Jose F.Abad and Georgia Panagopoulos, Ph.D. Gastroenterology, Lenox HillHospital, New York, NY and College of Medicine, State University ofNew York Health Science Center at Brooklyn, Brooklyn, NY.

S256 Abstracts AJG – Vol. 97, No. 9, Suppl., 2002