- Email: [email protected]
S35 Clinical utility of faecal calprotectin in diagnosing IBD during first presentation to the gastroenterology clinic: A novel investigative algorithm
32
5th International Meeting on Inflammatory Bowel Diseases, Capri, April 8 10, 2010
was characterized by the delayed beginning of effect and a wide spectrum of adverse reactions. Conclusion Effective treatment strategy of severe relapse of ulcerative colitis assumes earlier and more aggressive beginning of the “step-down” therapy. This approach combines earlier and adequate influence on immune-inflammatory mechanism of disease, safety and possibility of achieving full clinicalendoscopic remission with the majority of patients. S34 6-MP transport in human lymphocytes: Correlation with drug induced apoptosis in patients with IBD C. Cuffari, L. Conklin, X. Li. The Johns Hopkins University, Baltimore, MD, USA Introduction: Although 6-mercaptopurine (6-MP) and its prodrug azathioprine (AZA) have proven efficacy in the management of patients with IBD, there has been ongoing debate on the role of pharmacogenetic differences in thiopurine methyl transferase (TPMT) activity and 6-TGn metabolite levels in predicting responsiveness to therapy. Since most of these studies have been based on pharmacology of 6-MP metabolism in the red blood cell, it would seem likely that other putative genetic influences in the lymphocyte may be involved. It is our hypothesis that inherent differences in 6-MP transport may contribute to anti-metabolite resistance despite presumed therapeutic drug dosing and 6-TG metabolite levels. Aim: To characterize 6-MP transport in immortalized peripheral lymphocytes obtained from patients with IBD, and correlate intracellular levels with drug induced apoptosis. Methods: Intracellular accumulation of 6-MP was assayed in EBV-transformed human lymphocytes obtained from patients with IBD using 14 C-radiolabelled 6-MP. Cell proliferation was determined by MTT assay after incubation with various concentrations of 6-MP. Total cellular proteins and GADPH expression were analyzed as a measure of total surviving cells. RT-PCR was performed using gene-specific primers for 11 potential drug transporters. Results: Our results showed that intracellular drug accumulation occurs via active transport, is partially sodium dependent, and correlated with drug induced apoptosis independent of drug dosage and erythrocyte 6-TGn metabolite levels. Although none of the efflux transporters contribute to the variability of intra-cellular 6-MP accumulation, there was definite inherent variability among the influx transporters. Indeed, low expression of CNT-1, CNT-3, ENT-3 and ENT-4 associated well will low levels of intracellular 6-MP, and thus resistant to drug induced apoptosis. Conclusions: In summary, pharmacogenomic differences in clinical responsiveness to AZA therapy may also involve inherent differences in intracellular drug transport. Future studies are needed to best delineate the identity and role of these influx transporters in prospective clinical trials. S35 Clinical utility of faecal calprotectin in diagnosing IBD during first presentation to the gastroenterology clinic: A novel investigative algorithm C. Lees, A. Clark, A. Walkden, J. Satsangi, I. Arnott. Gastrointestinal Unit, University of Edinburgh, Scotland, UK Background: Whilst faecal calprotectin (FC) has been shown to distinguish reliably between functional and inflammatory bowel diseases (IBD), algorithms incorporating it into the initial diagnosis of IBD are presently lacking.
Aims: This study aimed to determine the optimal use of FC, in conjunction with serum markers, on first presentation to the gastroenterology clinic. Materials and Methods: Patients >50y were excluded, as they require colonoscopy to exclude malignancy. Detailed clinical, laboratory, endoscopic and radiological parameters were collected. Patients with a prior GI diagnosis were excluded. All stool samples were analysed in the same laboratory using the same FC assay. Patients were followed up for a minimum of 12 months. Results: The Edinburgh FC Register comprises data on 7512 patients (2005 2008). 1838/7512 were 16 50 y at time of time of first presentation to 2 teaching hospitals in Edinburgh. 987 (mean±SD age 33.5 ±9.0y; 64.8% female) met the strict inclusion criteria. Median FC was 20.0 (IQR: 20.0 51.0) in 639/987 (64.7%) who were ultimately diagnosed with a functional disorder, compared with 990.0 (IQR: 225.0 2190.0) in 113/987 (11.4%) with IBD (Lennard-Jones criteria). Analysis of covariance showed FC was influenced by NSAID use, but not by age, sex or smoking. In discriminating IBD from functional disease, sensitivities and specificities of FC were 97.5% and 0.49% at >20 mcg/g, 93.0% and 70.0% at >50 mcg/g, and 92.0% and 77.0% at >70 mcg/g. Further detailed analysis suggested the following model: FC < 70 mcg/g and normal blood parameters no further investigation; FC>50mcg/g with bloody diarrhoea OR raised CRP/hypoalbuminaemia combined radiological and endoscopic evaluation. Conclusions: In this study, the largest on the clinical utility of FC, we were able to develop clear investigative strategies in adults <50 yrs, dependent on FC and other clinical/laboratory parameters. This simple algorithm could be rolled out into primary care facilitating timely and appropriate triage of new patients and minimising diagnostic delay in IBD. S36 Medical therapies do not affect development of major complications and need for surgery in Crohn’s disease: A long-term prospective study E. Angelucci1 , M. Cesarini1 , P. Gentile2 , S. Necozione3 , G. Frieri2 , R. Caprilli1 , G. Latella2 . 1 GI Unit, University Sapienza, Rome, Italy, 2 Department of Internal Medicine and Public Health, GI Unit, University of L’Aquila, L’Aquila, Italy, 3 Department of Internal Medicine and Public Health, Clinical Epidemiology Unit, University of L’Aquila, L’Aquila, Italy Background and Aim: Natural history of Crohn’s disease (CD) is considered to be the result of the interaction between genetic factors, environment, disease behavior and medical therapies. Aim of this study is to prospectively evaluate the influence of demographic and clinical characteristics of patients, as well as medical therapies on the development of stricturing and penetrating complications and need for surgery. Materials and Methods: Out of a cohort of 603 CD patients followed at our GI Units, 193 consecutive patients (114 males, 79 females) with first diagnosis of CD made from 1998 to 2008 have been prospectively evaluated. Mean follow up was 59 months (range 12 120). Patients were classified according to the Vienna criteria. Sex, extraintestinal manifestations, family history of inflammatory bowel diseases, appendectomy, smoking habit and medical therapies (salicylates, antibiotics, steroids, immunosuppressants, anti-TNF-alpha antibodies) and surgical treatments performed during the follow-up period were assessed. Statistical analysis: Chi-squared test, Kaplan Meier survival method and Cox proportional hazards regression model. Results: Of the 193 patients, 11.9% had diagnosis of CD at surgery for acute abdomen. Disease localization remained
5th International Meeting on Inflammatory Bowel Diseases, Capri, April 8 10, 2010
was characterized by the delayed beginning of effect and a wide spectrum of adverse reactions. Conclusion Effective treatment strategy of severe relapse of ulcerative colitis assumes earlier and more aggressive beginning of the “step-down” therapy. This approach combines earlier and adequate influence on immune-inflammatory mechanism of disease, safety and possibility of achieving full clinicalendoscopic remission with the majority of patients. S34 6-MP transport in human lymphocytes: Correlation with drug induced apoptosis in patients with IBD C. Cuffari, L. Conklin, X. Li. The Johns Hopkins University, Baltimore, MD, USA Introduction: Although 6-mercaptopurine (6-MP) and its prodrug azathioprine (AZA) have proven efficacy in the management of patients with IBD, there has been ongoing debate on the role of pharmacogenetic differences in thiopurine methyl transferase (TPMT) activity and 6-TGn metabolite levels in predicting responsiveness to therapy. Since most of these studies have been based on pharmacology of 6-MP metabolism in the red blood cell, it would seem likely that other putative genetic influences in the lymphocyte may be involved. It is our hypothesis that inherent differences in 6-MP transport may contribute to anti-metabolite resistance despite presumed therapeutic drug dosing and 6-TG metabolite levels. Aim: To characterize 6-MP transport in immortalized peripheral lymphocytes obtained from patients with IBD, and correlate intracellular levels with drug induced apoptosis. Methods: Intracellular accumulation of 6-MP was assayed in EBV-transformed human lymphocytes obtained from patients with IBD using 14 C-radiolabelled 6-MP. Cell proliferation was determined by MTT assay after incubation with various concentrations of 6-MP. Total cellular proteins and GADPH expression were analyzed as a measure of total surviving cells. RT-PCR was performed using gene-specific primers for 11 potential drug transporters. Results: Our results showed that intracellular drug accumulation occurs via active transport, is partially sodium dependent, and correlated with drug induced apoptosis independent of drug dosage and erythrocyte 6-TGn metabolite levels. Although none of the efflux transporters contribute to the variability of intra-cellular 6-MP accumulation, there was definite inherent variability among the influx transporters. Indeed, low expression of CNT-1, CNT-3, ENT-3 and ENT-4 associated well will low levels of intracellular 6-MP, and thus resistant to drug induced apoptosis. Conclusions: In summary, pharmacogenomic differences in clinical responsiveness to AZA therapy may also involve inherent differences in intracellular drug transport. Future studies are needed to best delineate the identity and role of these influx transporters in prospective clinical trials. S35 Clinical utility of faecal calprotectin in diagnosing IBD during first presentation to the gastroenterology clinic: A novel investigative algorithm C. Lees, A. Clark, A. Walkden, J. Satsangi, I. Arnott. Gastrointestinal Unit, University of Edinburgh, Scotland, UK Background: Whilst faecal calprotectin (FC) has been shown to distinguish reliably between functional and inflammatory bowel diseases (IBD), algorithms incorporating it into the initial diagnosis of IBD are presently lacking.
Aims: This study aimed to determine the optimal use of FC, in conjunction with serum markers, on first presentation to the gastroenterology clinic. Materials and Methods: Patients >50y were excluded, as they require colonoscopy to exclude malignancy. Detailed clinical, laboratory, endoscopic and radiological parameters were collected. Patients with a prior GI diagnosis were excluded. All stool samples were analysed in the same laboratory using the same FC assay. Patients were followed up for a minimum of 12 months. Results: The Edinburgh FC Register comprises data on 7512 patients (2005 2008). 1838/7512 were 16 50 y at time of time of first presentation to 2 teaching hospitals in Edinburgh. 987 (mean±SD age 33.5 ±9.0y; 64.8% female) met the strict inclusion criteria. Median FC was 20.0 (IQR: 20.0 51.0) in 639/987 (64.7%) who were ultimately diagnosed with a functional disorder, compared with 990.0 (IQR: 225.0 2190.0) in 113/987 (11.4%) with IBD (Lennard-Jones criteria). Analysis of covariance showed FC was influenced by NSAID use, but not by age, sex or smoking. In discriminating IBD from functional disease, sensitivities and specificities of FC were 97.5% and 0.49% at >20 mcg/g, 93.0% and 70.0% at >50 mcg/g, and 92.0% and 77.0% at >70 mcg/g. Further detailed analysis suggested the following model: FC < 70 mcg/g and normal blood parameters no further investigation; FC>50mcg/g with bloody diarrhoea OR raised CRP/hypoalbuminaemia combined radiological and endoscopic evaluation. Conclusions: In this study, the largest on the clinical utility of FC, we were able to develop clear investigative strategies in adults <50 yrs, dependent on FC and other clinical/laboratory parameters. This simple algorithm could be rolled out into primary care facilitating timely and appropriate triage of new patients and minimising diagnostic delay in IBD. S36 Medical therapies do not affect development of major complications and need for surgery in Crohn’s disease: A long-term prospective study E. Angelucci1 , M. Cesarini1 , P. Gentile2 , S. Necozione3 , G. Frieri2 , R. Caprilli1 , G. Latella2 . 1 GI Unit, University Sapienza, Rome, Italy, 2 Department of Internal Medicine and Public Health, GI Unit, University of L’Aquila, L’Aquila, Italy, 3 Department of Internal Medicine and Public Health, Clinical Epidemiology Unit, University of L’Aquila, L’Aquila, Italy Background and Aim: Natural history of Crohn’s disease (CD) is considered to be the result of the interaction between genetic factors, environment, disease behavior and medical therapies. Aim of this study is to prospectively evaluate the influence of demographic and clinical characteristics of patients, as well as medical therapies on the development of stricturing and penetrating complications and need for surgery. Materials and Methods: Out of a cohort of 603 CD patients followed at our GI Units, 193 consecutive patients (114 males, 79 females) with first diagnosis of CD made from 1998 to 2008 have been prospectively evaluated. Mean follow up was 59 months (range 12 120). Patients were classified according to the Vienna criteria. Sex, extraintestinal manifestations, family history of inflammatory bowel diseases, appendectomy, smoking habit and medical therapies (salicylates, antibiotics, steroids, immunosuppressants, anti-TNF-alpha antibodies) and surgical treatments performed during the follow-up period were assessed. Statistical analysis: Chi-squared test, Kaplan Meier survival method and Cox proportional hazards regression model. Results: Of the 193 patients, 11.9% had diagnosis of CD at surgery for acute abdomen. Disease localization remained