A118 AGA ABSTRACTS

744

INFLAMMATORY BOWEL DISEASE, DISEASE COURSE ANDSTATUS 5 YEARS AFTER DIAGNOSIS.Jorgen lahnsen, Bjorn Mourn, Tom Schulz, Jostein Sauar, Idar Lygren,NjCEI Stray, Erling Aadland, Morten Vatn, Aker Univ Hosp, Oslo, Norway;-ss, Fredrikstad, Norway; Ass, Arendal, Norway; Tss, Skien, Norway;UllevCEI Univ Hosp, Oslo, Norway; Diakonhjemmet, Oslo, Norway; Rh,Oslo, Norway.

Background: Our knowledge concerning patients with inflammatory boweldisease (IBD) is mostly based on retrospective studies with registration ofpatients during a long time period. Aims: Evaluate changes in diagnosisand the clinical course of IBD during a 5 years follow-up period afterdiagnosis. Material and method: From 1990 to 94 we performed anincidens study in south-eastern Norway and 843 new cases of IBD werediagnosed. These patients have now been followed prospectively for 5years. Information concerning the course of the disease have been recordedmainly through clinical investigations and consultations. We have ex­cluded 114 patients (13.5%) from the study; 55 patients (6.5%) becausethey have died in the follow-up period and in 59 patients (7%) the datawere insufficient for evaluation. Results: Altogether 729 patients (87%) areevaluated; 445 with ulcerative colitis (UC) and 206 with Crohn's disease(CD). IBD was excluded in 73 patients (10%) after 5 years. Forty-twopatients (9%) with UC and 23 (11%) with CD had initially a differentdiagnosis. Patients with indeterminate colitis (IND) were all after fol­lOW-Up classified as either UC, CD or not IBD. Altogether 310 patients(70%) with UC and 157 (76%) with CD had at least one relapse duringfollow-up and 211 patients (49%) with UC and 106 (54 %) with CD hadone or more relapses during the last year. At the time of the evaluation 38patients (9 %) with UC and 32 (16%) with CD had considerable symptomsdue to the intestinal disease. Colectomy was performed in 34 patients(7.6%) with Uc. Among patients with CD, 55 (27%) were operated on withbowel resection and 18 (9%) have received surgical treatment for fistulaand/or abscess. Conclusion: In lout of 10 patients with diagnosed orsuspected lBO, the diagnosis was excluded after 5 years. All patients withIND were either classified as UC, CD or not IBO. Patients with CD hadmore frequent relapses and more symptoms than UC patients. The colec­tomy rate in UC is less compared to previous reports, while the risk ofsurgical intervention in CD is as found by others.

745

A PROSPECTIVE RANDOMIZED DOUBLE BLIND PLACEBOCONTROLLED STUDY TO ASSESS THE EFFICACY OF INTRA­VENOUS LOADING OF AZATillOPRINE IN CHILDREN ANDADOLESCENTS WITH INFLAMMATORY BOWEL DISEASE.Howard A. Kader, Yves Theoret, Vasundhara Tolia, Chris A. Liacouras,David A. Piccoli, Robert N. Baldassano, Div of Pediatric GIINutrition,Children's Hosp of Phila, Philadelphia, PA; Charles Bruneau Cancer Ctr,Hosp Ste-lustine, Montreal, Canada; Div of 01, Children's Hosp of Mich­igan, Detroit, MI; The Children's Hosp of Philadelphia, Philadelphia, PA.

Background: Oral azathioprine (AZA) is used to treat corticosteroid (CS)refractory and dependent IBD. The mean onset of action is delayed andoccurs at 4 months. Aims: (1) To determine the value of IV AZA loading,(2) to identify the safety profile for IV and oral AZA, and (3) to determinethe utility of measuring AZA metabolites. Methods: Patients were random­ized to receive an IV infusion of AZA, Group I; or placebo, Group 2, afterconfirming a high or normal TPMT activity, 13.8-25.1 U/ml RBC. An IVAZA dose of 30 mg/mvhr (maximum 50 mg/hr) for 24 hours was used.Patients began oral AZA, 2 mg/kg/day, after completion of the IV infusion.CS were weaned by weekly increments until discontinued or diseaserecurred. Disease activity was determined serially by the PCDAI or Seoactivity index. Blood samples for AZA metabolites were obtained concur­rently. AZA metabolite assays were performed as described by Cuffari etai, Gut 1996; 39:401-406. 6-TGN analysis was performed for study days42 through 84. Results: Fifteen patients with IBD were enrolled: II withCrohn's disease & 4 with ulcerative colitis. Eight patients received IV AZAand 7 patients received placebo. Two patients from each group wereexcluded from analysis for protocol violation as were I patient in Group 2who went to surgery and another in Group 2 who developed pancreatitis.Mean age was 13.1 :!:: 4.5 yrs old, range 6-19 yrs old. Mean diseaseduration was 30.3 :!:: 22.4 mths. Mean CS dose was 26.3 :!:: 12.6 mg. MeanTPMT activity was 18.1 :!:: 3.5 Vlml RBC. Complete remission (normaldisease activity index and off CS) occurred in 4/9 (44.4%) patients: 3/6(50.0%) in Group 1 and 1/3 (33.3%) in Group 2. Median time to completeremission was 3 mths, Patients who achieved complete remission had amean 6-TGN level of 224 :!:: 74 pmol/8x 108 RBC while patients who failedhad a mean 6-TGN level of 194 :!:: 59 pmol/8x1O RBC, p = NS.Significant adverse events occurred in 5/13 (38.5%) patients and werereversible. One patient with a median 6-MMP level of 6589 pmol/Sxl O"RBC developed hepatitis but 3 patients did not with median 6-MMP levelsof 6728, 6860, & 7443 pmol/Sxl O" RBC. Two patients developed leuko­penia with 6-TGN levels of 598 and 302 pmol/Sxl O" RBC, respectively.Conclusion: (1) IV loading of AZA does not accelerate the efficacy ofAZA. (2) AZA related adverse events are reversible. (3) There may be atrend towards complete remission with higher 6-TGN levels, but a largertrial is needed. (Funded by GCRC grant MOI-RR00240)

GASTROENTEROLOGY Vol. 118, No.4

746ALEXITHYMIA AND PSYCHOLOGICAL DISORDERS IN PA­TIENTS WITH INFLAMMATORY BOWEL DISEASE.George E. Kitis, Dimitrios A. Paikos, Maria Finiotou, Ioannis Gkioyuz­epas, Spyros Donias, G Papanikolaou Hosp, Thessaloniki, Greece.

Background: A correlation has been observed between psychopathologicalsymptoms and inflammatory bowel disease(IBD), especially ulcerativecolitis(UC). Alexithymia, (the inability to acknowledge and/or elaborateaffect, the inhibition of symbolic function with a preference for attendingto details of one's physical symptoms or environment, and a diminishedcapacity for fantasy) has also been reported in patients with IBD. Objec­tives: To investigate prospectively psychological disorders and alexithymiain patients with (IBD) during flares (f) or in remission (r ), compared tohealthy controls. Patients and methods: Twenty-five patients with UC(f=15, r=IO), 25 patients with CD(f=1I,r=14) and 31 healthy controlswere examined. They all answered questionnaires investigating the pres­ence of : ajalexithymia (Schalling-Syfneos Scale, SSS) and b) psychiatricsymptoms and especially: depression, anxiety, hostility/anger, somatiza­tion, obsessionality/compulsivity, interpersonal sensitivity, phobic anxiety,paranoid ideation, and psychoticism (Symptoms checklist 90 Rev, SCL­9OR). The scores obtained were analyzed by Student t-test. Results: Higherscores of alexithymia were obtained in patients with UC-r (36,3-p<0,00l),UC-f (34,78-p<0,001) and CD-r (34,64-p<0,05) compared to controls(24,03) but not in patients with CD-f. Likewise significantly higher scoresfor psychiatric parameters of depression, anxiety and hostility/anger wereobtained in patients with UC-f, UC-r, CO-f and CD-r compared to healthycontrols, with the exception of anxiety in CD-r. The anxiety score wassignificantly higher in UC compared to CD (14,8 vs. 9,97, p<0,05). Duringflares all scores were higher than in remission. No statistical differencesbetween patients and controls were observed in the scores of the otherpsychiatric parameters examined. Conclusions: Alexithymia is more prev­alent in patients with IBD than in controls and especially during remission,thus it is likely not a secondary phenomenon. Conversely depression,anxiety and hostility/anger are more prevalent during flares of IBD com­pared to controls, thus they are likely to be secondary psychologicalreactions to illness.

747THE ILEO NEO-RECTAL ANASTOMOSIS, A RESTORATIVEPROCEDURE FOR ULCERATIVE COLITIS AND FAMILIAL AD­ENOMATOUS POLYPOSIS WITHOUT A POUCH.Cees 1. Laarhoven, Gunnar I. Andriesse, Marguerite E. Schipper, Louis M.Akkermans, Theo 1. Vroonhoven, Hein G. Gooszen, Univ Med Ctr, Utre­cht, Netherlands.

The Ileo Pouch Anal Anastomosis (IPAA) is the generally applied restor­ative procedure in Ulcerative Colitis (UC) and Familial AdenomatousPolyposis (FAP) patients. This procedure however is attended by a highmorbidity (15-35% pouch related complications) and failure rate (6,5%).Essential developments in this operative procedure are not possible any­more and futher inprovements in the results are not to be expected. In needof a better alternative, the concept of the Ileo Neo-Rectal Anastomosis(INRA) was developed. After a subtotal colectomy and complete rectalmucosectomy, a vascularised ileal mucosa sling is created and transposedon to the denuded rectal cuff of about 15 centimeters. By immediatemucosal coverage and early growth of the mucosa into the rectal wall,contracture of the neo-rectum is prevented and its reservoir and evacuationcapacity are preserved. As a result the rectal excision and ileo analanastomosis, the stages of the IPAA procedure causing the above men­tioned complications, can be evaded in the INRA procedure. Moreoverformation of an ileum pouch has become unnecessary. After a successfulexperimental study in pigs to evaluate the technical feasibility, a humanpilot study was carried out. Untill now, twelve patients (10UC+2FAP) ina human pilot study received an INRA procedure with a temporary divert­ing ileostomy. No 'pouch'/ neo-recturn related complications occurred. Allmucosectomy specimens were histologically processed for assessment ofcompletenesss of resection. Repeated endoscopy and histological biopsiesshowed complete recovery and ingrowth of vital mucosa. All patients hadtheir temporary diverting ileostomy closed and now have a functionalneorectal reservoir. During the follow up (median 16 months, range 12-22months) the bowel frequency decreased from a initial median of 15x to 6x/24 hours (range 4-11). All patients are both passive and urge continent forstools and kept their normal evacuation capacity. Conclusion. The INRAprocedure with its ileum mucosa transposition to a denuded rectum isfeasible with a low complication rate. Complete removal of all diseasedcolorectal mucosa, and preservation of the (neo-)rectal reservoir withhealthy small bowel mucosa make the INRA procedure a promisingalternative to the IPAA procedure. A randomised multicenter study is beingprepared to compare the INRA and the IPAA operations.