whether sulfasalazine affects metabolism of or clinical response to 6-MP inpatients with Crohn’s disease.Methods: This is an ongoing, 16-week randomized, double-blind, placebo-controlled study in patients with Crohn’s disease who are starting therapywith 6-MP. Study subjects are started on 6-MP at a dose of 1.2 mg/kg and,in addition, are randomized to receive either sulfasalazine (SSZ) at a targetdose of 4 g/day or an identical appearing placebo. Exclusion criteria includelow TPMT enzyme activity, known sulfa allergy, and prior colectomy.Metabolic endpoints (6-MP metabolites, TPMT enzyme activity) and clin-ical endpoints (quality of life as assessed by IBDQ, Harvey-BradshawIndex [HBI]) are assessed at weeks 8 and 16. Preliminary week 8 results arepresented.Results: To date, 35 patients have met inclusion criteria and started 6-MPwith either SSZ or placebo. Of these patients, 19 were withdrawn from thestudy for the following reasons: allergic reaction to 6-MP (N�9 (26%); 3on SSZ and 6 on placebo), possible reaction to SSZ (N�6), other reactions(N�2), and non-compliance (N�2). Data for the remaining 16 patients arepresented in the table.

Sulfasalazine Placebo P-value

Number 7 9 -TPMT- Wk 0 35.4 � 10.5 33.1 � 6.8 0.6TPMT- Wk 8 36.6 � 4.5 37.9 � 6.5 0.66-TGN- Wk 8 333 � 95 265 � 142 0.36-MMP- Wk 8 3053 � 1553 5600 � 3344 0.096-MMP/6-TGN ratio 9.8 � 5.5 33.4 � 31.0 0.07IBDQ- Wk 0 152 � 33 160 � 25 0.6IBDQ- Wk 8 172 � 31 179 � 29 0.7HBI- Wk 0 5.0 � 2.5 3.6 � 2.6 0.3HBI- Wk 8 2.9 � 2.5 2.4 � 2.2 0.7

Conclusions: 1. In this prospective study, higher than expected rates of6-MP allergic reactions (26%) are noted. 2. In the SSZ group, there aretrends to lower 6-MMP levels and 6-MMP/6-TGN ratios. 3. Similar de-grees of clinical improvement are seen in both SSZ and placebo groups atweek 8. Further results from a larger dataset from this ongoing study willbe presented.

779

UTILITY OF SBFT TO ASSESS STRICTURING CROHNDISEASE OF SMALL INTESTINENooman Gilani, M.D.*, Rochelle Johns, M.D.,Francisco C. Ramirez, M.D., FACG, Miguel Regueiro, M.D. Universityof Pittsburgh Medical Center, Pittsburgh, PA and Carl.T.HaydenVAMC, Phoenix, AZ.

Purpose: CD is a chronic inflammatory disease of the GIT without aknown cure at present. Precise etiology is unclear, but appears to be adisease with AI features. Eighty to eighty-five percent of the patients haveSB involvement that in some leads to fibrosis and luminal strictures. Atpresent SBFT is the only avaiable modality to distinguish an acute flarefrom fibro-stenotic disease.We postulate that SBFT does not always diag-nose i.e. either misses or under diagnose the strictures and renders thesepatients to delay the appropriate treatment.Methods: Medical records of UPMC were searched retrospectively for thepast five years (95-00) using the MARS data, identifying 32 patients, 13M/19 F, mean age38 Y(23–55), Inclusion: Patients who underwent SBsurgery due to Crohn’s and had a SBFT at UPMC within 6 months of theoperation. Exclusion: SBFT done more than 6m prior to surgery or insuf-ficient details of SBFT /surgery. SBFT and surgical findings were com-pared. Pre-operative symptoms/disease duration/ steroid usage/ prior SBsurgical history was takenResults: Thirteen of twelve completely diagnosed;12 strictures (dist 11,prox 1), 1 normal. Inaccurate Dx: Overall 19/32 (59%), Stricture 15/29(52%) [missed 10, Overestimated 5] Fistulas 4/6. Total patients withstrictures 29; Identified: completely 16 (55%), partially 10 (35%), total 26

(90%) Missed: completely 3 (10%), partially 7(24%), total 10 (35%). Allpatients with strictures had obstructive symptoms except one without astricture upon surgery . 7/10 strictures missed in distal SB, 3/10 in mid SB.28/32 patients were on ch.steroids, 20/32 had a prior SB surgery. Diseaseduration was shorter in patients with missed strictures (13 vs 20 y). SBFT-Surgery time; Dx accurate, 7.28 W; Dx inaccurate, 9.71 W.

Overall Accuracy of SBFT in Identifying CD Strictures

SBFT Stricture (�) Stricture (-) Total

positive 26 02 28negative 03 01 04Total 29 03 32

sensitivity� 89%, specificity� 33%

Conclusions: SBFT is not an ideal test for diagnosing fibrotic strictures ofthe small bowel Crohn’s. Patients with longstanding Crohn, especially ifare steroid dependent or have previous SB resection, if present withpersistent obstructive GI symptoms, should initially be evaluated with aSBFT, but if negative and level of suspicion for stricture is high, should bereferred for surgical evaluation to prevent significant delay in the definitivetreatment. Larger prospective data is required to more accurately assess theefficacy of SBFT in this patient population. The role of capsule endoscopyneeds to be seen.

780

DOES AGGRESSIVE THERAPY FOR ILEAL CROHN’SDISEASE REDUCE THE NEED FOR SURGERYAbhijit Basu, M.D., Jeong Lee, M.D., Buyong Ahn, M.D.,Eric G. Weiss, M.D., Juan J. Nogueras, M.D., Gregory Bonner, M.D.,Steven D. Wexner, M.D.*. Cleveland Clinic Florida, Weston, FL.

Purpose: Patients with ileal and ileocolic Crohn’s disease often receiveaggressive and potentially toxic therapy in order to control disease activity.Accordingly, the effect of aggressive medical therapy on the need forsurgery in patients with ileal Crohn’s disease was studied.Methods: After Institutional Review Board approval, a retrospective re-view was undertaken of the medical records of all patients who were treatedfor ileal Crohn’s disease with aggressive medical therapy (high dosesteroids, immunosuppressives, and infliximab) and were available for fol-low. A control group of sixty consecutive patients who never receivedaggressive therapy was chosen for comparison. Patients were identifiedfrom a prospective database.Results: The medical records of 205 patients were reviewed, 145 patientsin the aggressive therapy group and 60 patients on standard therapy(control). Data were incomplete on 3 patients and were excluded, leaving143 patients in the aggressive therapy group and 59 controls. Medianduration of aggressive therapy was 3.5 years, the median duration ofdisease was 14 (range 1 to 59) years, the mean duration of steroid use was98 weeks, the mean (range) dose of prednisone was 40.9 (20 to 60) mg perday and the mean duration of 6MP and methotrexate use was 95 and 45weeks respectively in a total of 96 patients. 29 patients received infliximab(1 to 10 doses). Among 59 patients on standard therapy, 31 (53%) requiredan operation. Among patients on aggressive therapy, 83 did not have anyoperation before commencing aggressive therapy; 34 of these 83 patients(41%) required an operation despite being on aggressive therapy (p � 0.11;Fishers exact test). 15 (25%) of the remaining 60 patients in this grouprequired surgery for recurrent disease despite receiving aggressive therapy.Conclusions: Aggressive therapy does not lead to a significant reduction inthe need for surgery compared with standard medical therapy. Thus, therisks of aggressive therapy should be carefully considered when offering itto patients whose symptoms are not controlled by standard medicationsalone.

S259AJG – September, Suppl., 2003 Abstracts

781

PYLORIC GLAND METAPLASIA- A SPECIFICHISTOPATHOLOGIC MARKER FOR CROHN’S DISEASEJhony Doumit, M.D., Bo Shen, M.D.*, John Goldblum, M.D.,Jason Connor, M.S., Jean-Paul Achkar, M.D., Aaron Brzezinski, M.D.,Fran Herron, Muhammad Alam, M.D., Charles Bevins, M.D.,Bret Lashner, M.D. The Cleveland Clinic Foundation, Cleveland, OH.

Purpose: To assess sensitivity, specificity, and positive (PPV) and negative(NPV) predictive values of PGM in the diagnosis of CD. Distinguishingcolonic Crohn’s disease (CD) from ulcerative colitis (UC) is important butcan sometimes be difficult. It has been noticed that pyloric gland metaplasia(PGM) of the intestinal and colonic mucosa is more often seen in CD thanin UC. However, the significance and possible diagnostic value of PGM hasnot been systematically evaluated.Methods: We retrospectively reviewed the pathology reports of 2483 casesof inflammatory bowel disease (endoscopic biopsy and surgically resectedspecimens), diagnosed by one of four gastrointestinal pathologists between1999 and 2002. Diagnosis of CD, UC, or indeterminate colitis (IC) wasbased on combined assessment of clinical, endoscopic, radiographic, andhistopathologic features. Jeffries confidence intervals for a proportion wereused to estimate sensitivity, specificity, PPV, and NPV.

Anatomic Distribution of 49 Cases Reported Having PGM

Crohn’sDisease

UlcerativeColitis

Indeter.Colitis

Total number of Cases 1125 921 437Cases with Pyloric Gland Metaplasia (%) 45 (4%)* 1 (0.1%) 3 (0.7%)PGM Locations: Sm Bowel only/Colon

only/Sm bowel & Colon30/7/8 1/0/0 2/1/0

* CD vs UC and IC, P � 0.001

Diagnostic Accuracy Using PGM Present in the Small Bowel or Colon (95% CI)

Sensitivity Specificity PPV NPV

CD vs UC 4.0 (2.9–5.2) 99.9 (99.5–99.99) 97.8 (90.3-99.8) 45.9 (43.7–48.1)CD vs UC

& IC4.0 (2.9–5.2) 99.7 (99.3–99.9) 91.8 (81.8–97.2) 55.7 (53.7–57.7)

Conclusions: Although PGM is a rare finding in mucosal histopathology,it is specific for Crohn’s disease with a high positive predictive value.

782

SURGERY IMPROVES EXTRAINTESTINALMANIFESTATIONS OF MUCOSAL ULCERATIVE COLITISAbhijit Basu, M.D., Steven D. Wexner, M.D.*, Eric G. Weiss, M.D.,Juan J. Nogueras, M.D., Gregory Bonner, M.D. Cleveland ClinicFlorida, Weston, FL.

Purpose: The aim of this study was to study extraintestinal manifestations(EIM) of patients with mucosal ulcerative colitis (MUC) before and afterrestorative proctocolectomy and to compare the results in patients nothaving surgery.Methods: After Institutional Review Board approval, patients who hadproctocolectomy and had EIMs were identified by retrospective chartreview and by a postal questionnaire. A control group of 100 consecutivepatients with pancolitis not undergoing surgery were studied similarly.Evolution of the EIMs was classified as worsened, remained unchanged,improved or disappeared. The outcomes of the EIMs were comparedbetween the surgical patients and those not having surgery.Results: Sixty-six EIMs were observed in 46 surgical patients and 22 EIMsin 14 medical patients. Among medically treated patients improvement orcure was observed in only 14% EIMs whereas 58% of EIMs were cured orimproved in patients undergoing proctocolectomy (p � 0.02, Chi squaretest). Arthralgia or arthritis was the commonest manifestations in both thesurgical (75%) and medical (73%) patients. Improvement after surgery was

noted in most EIMs. Among surgical patients, improvement was mostsignificant (100%) in erythema nodosum, pyoderma gangrenosum, uveitis,venous thromboembolism and less significant in aphthous oral ulceration(88%), ankylosing spondylitis (56%) and arthralgia (46%). Overall, EIMsremained unchanged in 77 vs 23%, worsened in 9 vs 19%, disappeared in9 vs 26% and improved in 5 vs 32%, in the medical versus surgical patients,respectively.Conclusions: Significant improvement occurred in all EIMs. Erythemanodosum, uveitis, and arthralgias are EIMs that affect quality of life andeither disappeared or improved in a significant proportion of patients.Patients with pancolitis should be evaluated for EIMs when consideringchoice of therapy.

783

THE SAFETY OF BUDESONIDE: A GLOBAL ANALYSISGary R. Lichtenstein, M.D.*, Bengt Bengtsson, M.D.,Louise Hapten-White, R.N. Hospital of the University of Pennsylvania,Philadelphia, PA and AstraZeneca, Lund, Sweden.

Purpose: To evaluate the safety profile of budesonide capsules (BUD) inpatients treated for mild to moderate Crohn’s disease (CD) in all short- andlong-term controlled studies performed to date.Methods: Safety data from all Phase IIB-III controlled, prospective, ran-domized, double-blind clinical studies evaluating BUD for CD involvingileum and/or ascending colon were assessed. Adverse events (AEs) re-ported for BUD were compared with AEs for prednisolone (PRED) andwith AEs for placebo in studies of short and long duration.Results: Incidence rates of AEs � 5% Table 1.

Short-Term Long-Term

Side EffectsBUD 9 mg(n � 520)

PRED 40mg taper(n � 145)

Placebo(n � 107)

BUD 3and 6 mg(n � 296)

Placebo(n � 209)

Cutaneous GCS1 34%2 48% 27%3 30%4 20%Upper GI symptoms 29% 37% 21% 23% 18%Respiratory infections 22% 23% 22% 19% 21%Psychiatric disorders 21%4,5 43% 11%3 15% 14%Resistance mechanism

disorders67% 7% 8% 11% 5%

Mestual disorders 7% 11% 2% 5% 1%

1 Includes acne, moon face, easy bruisability, swollen ankles, hirsutism, skin striae,and buffalo hump; 2 P�.01 vs PRED; 3 P�.05 vs PRED; 4 P�.05 vs placebo;5 P�.001 vs PRED; 6 Immune responses that may be aggravated by treatment;includes viral infections.

For most of the glucocorticosteroid (GCS)-related systemic side effects, theincidence of AEs with BUD did not statistically differ from placebo. Forsome short-term side effects (cutaneous GCS and psychiatric disorders)there was a higher incidence of AEs in BUD-treated patients than inplacebo patients; however, these AEs were significantly lower in BUDpatients versus PRED. In long-term studies, only cutaneous GCS sideeffects showed a higher incidence in the BUD group compared withplacebo. It should be noted that all the presented AEs are not necessarilynewly emergent; ie, these AEs may have been present in those patientsswitched from PRED to BUD at the initiation of the long-term studies. Thismay explain the relatively high rates of GCS side effects seen.Conclusions: Significantly fewer GCS side effects were reported in short-term studies with BUD than with systemic steroids. A similar rate of mostside effects was observed with BUD compared with placebo in both short-and long-term studies.

784

IS IMMUNOMODULATOR MONOTHERAPY ENOUGH TOMAINTAIN REMISSION IN CROHN’S DISEASE?Denise P. Guarino, R.P.A.-C., Gerard E. Mullin, M.D.*. North ShoreUniversity Hospital, Manhasset, NY.

S260 Abstracts AJG – Vol. 98, No. 9, Suppl., 2003