1
Conclusions: No statistically significant differences were seen in compar- ing CD patients with BMI25 to those with BMI25 when examining time to diagnosis or duration of disease of CD. This data is encouraging, as it suggests that gastroenterologists are unbiased when evaluating inflam- matory symptoms, and retain broad differential diagnoses in order to accurately arrive at the correct disease pathology. 735 ANTI-INFLAMMATORY PROPERTIES OF STATINS IN THE DEXTRAN SODIUM SULFATE MOUSE MODEL OF COLITIS Jong H. Nam, M.D., Zaid Alnoah, M.M.S., Sreekant N. Murthy, Ph.D.*. Drexel University College of Medicine, Philadelphia, PA. Purpose: HMG-CoA reductase inhibitors, or “statins”, have demonstrated anti-inflammatory effects in animal models of atherosclerosis in addition to their lipid-lowering effects. The purpose of this experiment was to assess the anti-inflammatory effects of statins in the dextran sodium sulfate (DSS) mouse model of colitis, a well-established murine model of colonic in- flammation. Methods: Eighteen 8-week old female Swiss-Webster mice were separated into three groups of 6. Colitis was induced in all animals by feeding 4% DSS solution ad libitum for 7 days. Following discontinuation of DSS, groups 1 and 2 received oral atorvastatin (60 mg/kg/day) and simvastatin (20 mg/kg/day), respectively, suspended in 0.75% methyl-cellulose for the next 8 days. Group 3 served as control and received oral methyl-cellulose only. A disease activity index (DAI) was determined on a daily basis for all animals throughout the study, and consisted of a calculated score based on change in body weight, stool consistency, and intestinal bleeding. The DAI is a well-characterized method of quantifying disease severity in this model and is known to correlate well with histological healing. Parameters for the DAI were measured by an investigator who was blinded to the protocol. All animals were sacrificed on day 14. Colon lengths were measured as an additional indicator of disease activity. Results: On day 15, the control group demonstrated a mean DAI of 1.94 0.49. Group 1, in comparison, demonstrated a significantly lower mean DAI of 0.78 0.72 (P 0.01). Group 2, likewise, demonstrated a much lower mean DAI of 0.72 0.7 (P 0.01). When colon lengths were assessed, atorvastatin and simvastatin treated groups showed significantly greater average colon lengths (6.83 0.21 and 7.33 0.95 cm, respec- tively) than that of the control group (6.15 0.54 cm; P 0.05). Conclusions: Our data demonstrates the anti-inflammatory properties of statins in a murine model of colitis for the first time to our knowledge. Further investigation is clearly needed to elucidate the mechanism of anti-inflammatory properties of statins. 736 IRON DEFICIENCY ANEMIA AS A PRESENTATION OF POUCHITIS Rafael J. Pastrana, M.D., Esther A. Torres, M.D., FACG*, Cynthia Rivera, M.P.H., Jesus Arroyo, M.D., Maria Vazquez, M.D., Luis Flores, M.D. UPR School of Medicine, San Juan, PR, Puerto Rico. Purpose: Ileal pouch with anal anastomosis (IPAA) has become the surgical procedure of choice in Ulcerative Colitis (UC) patients. Among its described complications are pouchitis (40%), strictures (30%), small bowel obstruction (10%), pelvic sepsis (5%), and urinary and sexual dysfunc- tions (5%). Few studies have described the prevalence of anemia after IPAA but no conclusive findings have been reported at present. Anemia may serve as a follow up screening tool for pouchitis surveillance. This study sought (1) to determine the prevalence and cause of anemia in patients undergoing IPAA for UC, and (2) to correlate anemia with com- plications after IPAA. Methods: The study was approved by the IRB of the UPR. Informed consent was obtained from all study participants. Patients with diagnosis of UC by clinical, histological, endoscopic, radiological, or surgical/patho- logical criteria who had undergone IPAA were recruited from the UPR IBD and Faculty clinics and GI Research Unit. Pertinent demographics and medical data were obtained. Blood serum samples were obtained from the subjects to establish the presence of anemia by standard hematological values. Those patients found with anemia were further evaluated with serum levels of iron, ferritin, transferrin, folate, vitamin B-12, erythropoi- etin, total iron binding capacity, reticulocyte counts, peripheral smears, and bone marrow aspirates. Data analysis was performed with EPI Info Version V 6.0. Results: A total of 16 subjects were included. Mean age was 37.0 14.7 years. Male to female ratio was 1:1.6. Average Hemoglobin/ Hematocrit levels were 11.7 2.7/35.5 7.25 gm/dl. Mean follow up was 2 years after surgery. Iron deficiency anemia was identified in 62.5% (10/16) of study subjects, of which only 63.6% (7/11) had clinical, endoscopic, or histologic evidence of pouchitis. Four of the patients without anemia had evidence of pouchitis (36.4%). Results Anemia n10 No Anemia n6 Pouchitis n11 7 (43.8%) 4 (25%) No Pouchitis n5 3 (18.7%) 2 (12.5%) Conclusions: A trend suggesting that iron deficiency anemia may be a complication of IPAA and a presenting clinical sign of pouchitis was observed. A larger number of patients is needed to confirm these findings. Hemoglobin and Hematocrit levels may be considered as a surveillance tool in patients with IPAA. 737 PRIOR AMINOSALICYLATE USE AND THE DEVELOPMENT OF COLORECTAL CANCER IN INFLAMMATORY BOWEL DISEASE (IBD): A LARGE BRITISH EPIDEMIOLOGICAL STUDY T.P. van Staa, M.D., Ph.D., T. Card, M.Sc., M.R.C.P., H.G.M. Leufkens, Ph.D., R.F. Logan, M.Sc., F.R.C.P.*. Procter & Gamble Pharmaceutical, Egham, United Kingdom; Utrecht Institute for Pharmaceutical Sciences, Utrecht, Netherlands and Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom. Purpose: The objective of this study was to evaluate the risk of colorectal cancer (CRC) in patients using aminosalicylates (5-ASA) for IBD. Methods: The medical records of general practitioners (GPs) in the UK (from the General Practice Research Database) were used. This database has been previously demonstrated to be a representative sample of the general population of England and Wales. The study population consisted of either users of mesalazine, balsalazide, olsalazine, or sulfasalazine with a history of IBD. In a nested case-control analysis, each incident CRC case with any exposure to 5-ASA within 6 months of the CRC diagnosis was matched by age, sex, and calendar time to six control patients who were also exposed in that period. Patients were then classified according to regularity of use. Regular users were those who had received six or more 5-ASA prescriptions in the 12 months before. The analysis was controlled for history of colorectal polyps, use of NSAIDs, paracetamol, aspirin, oral and rectal corticosteroids and disease-modifying agents, IBD duration, prior hospitalisation and number of GP visits for IBD symptoms. Addi- tional data on the extent and activity of IBD in this population will be collected. Results: The study population included 18 969 patients, of whom 100 patients had developed CRC. Most of these cases had a history of ulcerative colitis (76 patients). In the nested case-control analysis, regular users were found to have a decreased risk of CRC compared to irregular users (crude OR 0.67 [0.44 –1.03]; adjusted OR 0.54 [0.35– 0.86]). The adjusted OR in patients with regular use for 2 years was 0.61 [0.32–1.16] and 0.51 [0.30 – 0.87] with use 2 years. Regular users of sulfasalazine with 6 to 12 S244 Abstracts AJG – Vol. 98, No. 9, Suppl., 2003

Iron deficiency anemia as a presentation of pouchitis

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Page 1: Iron deficiency anemia as a presentation of pouchitis

Conclusions: No statistically significant differences were seen in compar-ing CD patients with BMI�25 to those with BMI�25 when examiningtime to diagnosis or duration of disease of CD. This data is encouraging, asit suggests that gastroenterologists are unbiased when evaluating inflam-matory symptoms, and retain broad differential diagnoses in order toaccurately arrive at the correct disease pathology.

735

ANTI-INFLAMMATORY PROPERTIES OF STATINS IN THEDEXTRAN SODIUM SULFATE MOUSE MODEL OF COLITISJong H. Nam, M.D., Zaid Alnoah, M.M.S., Sreekant N. Murthy, Ph.D.*.Drexel University College of Medicine, Philadelphia, PA.

Purpose: HMG-CoA reductase inhibitors, or “statins”, have demonstratedanti-inflammatory effects in animal models of atherosclerosis in addition totheir lipid-lowering effects. The purpose of this experiment was to assessthe anti-inflammatory effects of statins in the dextran sodium sulfate (DSS)mouse model of colitis, a well-established murine model of colonic in-flammation.Methods: Eighteen 8-week old female Swiss-Webster mice were separatedinto three groups of 6. Colitis was induced in all animals by feeding 4%DSS solution ad libitum for 7 days. Following discontinuation of DSS,groups 1 and 2 received oral atorvastatin (60 mg/kg/day) and simvastatin(20 mg/kg/day), respectively, suspended in 0.75% methyl-cellulose for thenext 8 days. Group 3 served as control and received oral methyl-celluloseonly. A disease activity index (DAI) was determined on a daily basis for allanimals throughout the study, and consisted of a calculated score based onchange in body weight, stool consistency, and intestinal bleeding. The DAIis a well-characterized method of quantifying disease severity in this modeland is known to correlate well with histological healing. Parameters for theDAI were measured by an investigator who was blinded to the protocol. Allanimals were sacrificed on day 14. Colon lengths were measured as anadditional indicator of disease activity.Results: On day 15, the control group demonstrated a mean DAI of 1.94 �0.49. Group 1, in comparison, demonstrated a significantly lower meanDAI of 0.78 � 0.72 (P � 0.01). Group 2, likewise, demonstrated a muchlower mean DAI of 0.72 � 0.7 (P � 0.01). When colon lengths wereassessed, atorvastatin and simvastatin treated groups showed significantlygreater average colon lengths (6.83 � 0.21 and 7.33 � 0.95 cm, respec-tively) than that of the control group (6.15 � 0.54 cm; P � 0.05).Conclusions: Our data demonstrates the anti-inflammatory properties ofstatins in a murine model of colitis for the first time to our knowledge.Further investigation is clearly needed to elucidate the mechanism ofanti-inflammatory properties of statins.

736

IRON DEFICIENCY ANEMIA AS A PRESENTATION OFPOUCHITISRafael J. Pastrana, M.D., Esther A. Torres, M.D., FACG*,Cynthia Rivera, M.P.H., Jesus Arroyo, M.D., Maria Vazquez, M.D.,Luis Flores, M.D. UPR School of Medicine, San Juan, PR, PuertoRico.

Purpose: Ileal pouch with anal anastomosis (IPAA) has become thesurgical procedure of choice in Ulcerative Colitis (UC) patients. Among itsdescribed complications are pouchitis (40%), strictures (30%), small bowelobstruction (10%), pelvic sepsis (�5%), and urinary and sexual dysfunc-tions (�5%). Few studies have described the prevalence of anemia afterIPAA but no conclusive findings have been reported at present. Anemiamay serve as a follow up screening tool for pouchitis surveillance. Thisstudy sought (1) to determine the prevalence and cause of anemia inpatients undergoing IPAA for UC, and (2) to correlate anemia with com-plications after IPAA.Methods: The study was approved by the IRB of the UPR. Informedconsent was obtained from all study participants. Patients with diagnosis ofUC by clinical, histological, endoscopic, radiological, or surgical/patho-

logical criteria who had undergone IPAA were recruited from the UPR IBDand Faculty clinics and GI Research Unit. Pertinent demographics andmedical data were obtained. Blood serum samples were obtained from thesubjects to establish the presence of anemia by standard hematologicalvalues. Those patients found with anemia were further evaluated withserum levels of iron, ferritin, transferrin, folate, vitamin B-12, erythropoi-etin, total iron binding capacity, reticulocyte counts, peripheral smears, andbone marrow aspirates. Data analysis was performed with EPI Info VersionV 6.0.Results: A total of 16 subjects were included. Mean age was 37.0 � 14.7years. Male to female ratio was 1:1.6. Average Hemoglobin/ Hematocritlevels were 11.7 � 2.7/35.5 � 7.25 gm/dl. Mean follow up was 2 yearsafter surgery. Iron deficiency anemia was identified in 62.5% (10/16) ofstudy subjects, of which only 63.6% (7/11) had clinical, endoscopic, orhistologic evidence of pouchitis. Four of the patients without anemia hadevidence of pouchitis (36.4%).

Results

Anemian�10

No Anemian�6

Pouchitis n�11 7 (43.8%) 4 (25%)No Pouchitis n�5 3 (18.7%) 2 (12.5%)

Conclusions: A trend suggesting that iron deficiency anemia may be acomplication of IPAA and a presenting clinical sign of pouchitis wasobserved. A larger number of patients is needed to confirm these findings.Hemoglobin and Hematocrit levels may be considered as a surveillancetool in patients with IPAA.

737

PRIOR AMINOSALICYLATE USE AND THE DEVELOPMENTOF COLORECTAL CANCER IN INFLAMMATORY BOWELDISEASE (IBD): A LARGE BRITISH EPIDEMIOLOGICALSTUDYT.P. van Staa, M.D., Ph.D., T. Card, M.Sc., M.R.C.P.,H.G.M. Leufkens, Ph.D., R.F. Logan, M.Sc., F.R.C.P.*. Procter &Gamble Pharmaceutical, Egham, United Kingdom; Utrecht Institute forPharmaceutical Sciences, Utrecht, Netherlands and Division ofEpidemiology and Public Health, University of Nottingham, Nottingham,United Kingdom.

Purpose: The objective of this study was to evaluate the risk of colorectalcancer (CRC) in patients using aminosalicylates (5-ASA) for IBD.Methods: The medical records of general practitioners (GPs) in the UK(from the General Practice Research Database) were used. This databasehas been previously demonstrated to be a representative sample of thegeneral population of England and Wales. The study population consistedof either users of mesalazine, balsalazide, olsalazine, or sulfasalazine witha history of IBD. In a nested case-control analysis, each incident CRC casewith any exposure to 5-ASA within 6 months of the CRC diagnosis wasmatched by age, sex, and calendar time to six control patients who werealso exposed in that period. Patients were then classified according toregularity of use. Regular users were those who had received six or more5-ASA prescriptions in the 12 months before. The analysis was controlledfor history of colorectal polyps, use of NSAIDs, paracetamol, aspirin, oraland rectal corticosteroids and disease-modifying agents, IBD duration,prior hospitalisation and number of GP visits for IBD symptoms. Addi-tional data on the extent and activity of IBD in this population will becollected.Results: The study population included 18 969 patients, of whom 100patients had developed CRC. Most of these cases had a history of ulcerativecolitis (76 patients). In the nested case-control analysis, regular users werefound to have a decreased risk of CRC compared to irregular users (crudeOR 0.67 [0.44–1.03]; adjusted OR 0.54 [0.35–0.86]). The adjusted OR inpatients with regular use for � 2 years was 0.61 [0.32–1.16] and 0.51[0.30–0.87] with use � 2 years. Regular users of sulfasalazine with 6 to 12

S244 Abstracts AJG – Vol. 98, No. 9, Suppl., 2003