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Transmural Healing is Better than Mucosal Healing in Crohn's Disease
Characteristics of the study population
AGA Abstracts
reference standard. MTR was evaluated as secondary and apparent diffusion coefficient (ADC) as exploratory objective. Methods: Informed consent was obtained from 51 stenotic CD patients eligible for resection surgery across 6 European centers in a prospective trial evaluating MRE for the detection of fibrosis in CD. Imaging was performed a median of two weeks (>90% <8 weeks) prior to surgery with no treatment changes in between. Local pathologists and radiologists annotated the location of 56 histological samples on the MRE scans, which was identified in the most stenosed region of corresponding resected specimens. An experienced pathologist centrally read the 56 samples using the Chiorean score.2 A single radiologist measured DGE, MTR, T2, ADC, and MaRIA index.1, 3 Correlation of histology and MRE metrics was performed using Pearson's R. Results: No association of fibrosis or inflammation with either DGE or MTR was found (fig 1). ADC was associated with fibrosis (R=-0.36, p=0.011). MaRIA score was correlated with inflammation (0.31, 0.031). Monitoring of image data quality by central reader resulted in >95% evaluable scans. Conclusions: In this prospective, multi-center study, DGE and MTR were not found to be in concordance with histological measure of fibrosis, in contrast to previously published findings. This may have been due to a spatial mismatch between histological tissue sample and imaging measurement region of interest, inconsistencies in the interval between imaging and surgery, the effects of histological preparation, or lack of granularity in histological scoring. However MaRIA scores were in good agreement with inflammation scoring, so it is possible that MRE metrics assist in the assessment of CD stenosis. Further development of histological scores and MRE metrics will inform upon MRE protocol development in CD. References: 1. Rimola J, et al. Am J Gastroenterol 2015. 2. Pazahr S, et al. MAGMA 2013. 3. Rimola, J, et al. Gut 2009.
TH, transmural healing; MH, mucosal healing; NH, no healing; SD, standard deviation
Mo1750 DISAGREEMENT AMONG GASTROENTEROLOGISTS IN THE ENDOSCOPIC EVALUATION USING THE MAYO ENDOSCOPIC SCORE AND THE RUTGEERTS POSTOPERATIVE SCORE Samuel Fernandes, João Pinto, Pedro M. da Costa, Luís Correia BACKGROUND: Endoscopic evaluation is an integral part in the evaluation of patients with Inflammatory bowel disease (IBD). Endoscopy is routinely used by most clinicians to evaluate disease severity and guide important clinical decisions. Therefore, variability in the interpretation of endoscopic findings amongst different gastroenterologists represents a problem of the upmost importance, which can severely impact the management of patients with IBD. OBJECTIVES: To study the inter-rater variability using the Mayo endoscopic subscore (MS) and Rutgeerts score (RS) amongst gastroenterologists. METHODS: Several gastroenterologists were invited to participate in an online survey including pictures and videos from patients with Crohn's disease (CD) and Ulcerative Colitis (UC), 20 questions. Participants were asked to rate the mucosal appearance in UC using the MS (0-3), and the neo-terminal ileum, anastomosis, and proximal colon in operated patients with CD using the RS (0-4). To assess the impact of clinical information on scoring, 2 identical questionnaires differing on the clinical information provided on 6 cases were used. In the second part, participants were able to consult the scores prior to answering the questions. The inter-rater concordance (IRC) was assessed using Krippendorff's alpha test. RESULTS: 58 gastroenterologists agreed to participate in the study. Nineteen (32.8%) stated to have more experience in IBD (seeing >10 patients/week), 50 (86.2%) performed endoscopy in IBD, and 52 (89.7%) routinely used the scores. The IRC for the MS and RS was 0.47 95%CI (0.41-0.54) and 0.33 95%CI (0.28-0.38). There was no influence of clinical information on the IRC for the MS (p=0.762) or the RS (p=0.147). Consultation of scores slightly improved the IRC for the MS [0.50 95%CI (0.42-0.58) vs 0.45 95%CI(0.38-0.51)], but not the RS [0.16 95%CI (0.10-0.21) vs 0.41 95%CI (0.35-0.46)]. The IRC for mucosal healing (MS≤1) and deep mucosal healing (MS=0) was 0.57 95%CI (0.40-0.72) and 0.89 95%CI (0.73-1). The IRC for postoperative recurrence (RS≥i2) was only 0.44 95%CI (0.24-0.62) and for severe recurrence (RS≥3) 0.54 95%CI (0.36-0.71). Considering the 18 participants stating to be more proficient in IBD (consults, endoscopy and scores), the IRC increased for the MS [0.54 95%CI (0.46-0.60)] and RS [0.42 95%CI (0.37-0.47)]. In this group, the IRC was also higher for mucosa healing (MS≤1) [0.62 95%CI (0.45-0.78)], deep mucosal healing (MS=0) [0.89 95%CI (0.75-1)], postoperative recurrence (RS≥2) [0.58 95%CI (0.39-0.76)], and severe postoperative recurrence (RS≥3) [0.59 95%CI (0.42-0.75)]. DISCUSSION: Our study confirms a high interrater disagreement amongst gastroenterologists using the MS and the RS, even amongst experienced physicians. Worryingly, there was only a moderate concordance for the most important outcomes- mucosal healing and postoperative recurrence.
Histological fibrosis (top) and inflammation scores (bottom) plotted against MRE parameters. ADC was associated with fibrosis. Inflammation was associated with MaRIA score.
Mo1749 TRANSMURAL HEALING IS BETTER THAN MUCOSAL HEALING IN CROHN'S DISEASE Samuel Fernandes, Rita Vale Rodrigues, Sónia Bernardo, João Cortez-Pinto, Isadora Rosa, Luís Correia, Cilénia Baldaia, Paula Moura-Santos, Ana R. Gonçalves, Ana Valente, João Pereira da Silva, António Dias Pereira, José Velosa BACKGROUND: Mucosal healing (MH) is currently accepted as the optimal target in Crohn's disease (CD), and is associated with improved long-term outcomes including reduced hospitalizations and surgery. However, even in patients with sustained MH, residual transmural inflammation may persist. The benefit of obtaining complete transmural healing (TH), have not been previously assessed. The aim of the study was to evaluate the long-term outcomes of TH in patients with CD. METHODS: This was a multicenter observational study including patients from a prospective database of Inflammatory bowel disease (Grupo de Estudos de Doença Inflamatória Intestinal). Patients with CD with a MRI-enterography (MRE) and colonoscopy performed in a 6-month interval were included. MRE was classified as active/ inactive based on the presence of abnormal bowel wall thickening, contrast enhancement, fat creeping, Comb sign, and complications (stricture, abscess or fistula). In non-operated patients, colonoscopy was classified as active/inactive based on the presence of ulceration. In operated patients, colonoscopy was classified as active/inactive if the Rutgeerts score was ≥i2. We defined 3 groups: TH (inactive MRE with inactive colonoscopy); MH (active MRE with inactive colonoscopy), No healing (NH) (active colonoscopy). We evaluated several outcomes at 1 year including the need for surgery, hospital admission, therapy escalation (immunomodulator, biologic or escalation of biologic), and a compound outcome including any of the former. Patients with inflammation restricted to the colon were excluded. RESULTS: A total of 214 patients [TH (n=33), MH (n=52), NH (n=129)], 91 (41.7%) previously operated, were included in the study. MRE and colonoscopy showed active inflammation in 162 (74.3%) and 132 patients (60.6%), respectively. At 12 months, patients with TH showed lower rates of hospital admission than patients with MH and NH (6.1% versus 17.3%, p=0.188 (n.s.) and 24.0%, p=0.014), therapy escalation (15.2% versus 36.5%, p= 0.027 and 54.3%, p<0.001), surgery (0% versus 11.5%, p=0.047 and 11.6%, p= 0.027), and any outcome (18.2% versus 44.2%, p=0.011 and 63.6%, p<0.001). Patients with TH showed longer times to surgery (p=0.045 and p=0.044 for MH and NH), therapy escalation (p=0.046 and p<0.001 for MH and NH), and to reach any endpoint (p=0.019 and p<0.001 for MH and NH). Increasing age at evaluation (OR 0.971 95%CI [0.951-0.992], p=0.006), MH (OR 0.384 95%CI [0.208-0.707], p=0.002), and TH (OR 0.336 95%CI [0.171-0.660, p=0.002] were independently associated with a lower likelihood of reaching the compound outcome. DISCUSSION: TH is associated with improved long-term outcomes in patients with CD, including lower risk of hospital admission, therapy escalation and surgery. Our data suggests that TH is a more suitable target than MH in CD.
Mo1751 DETECTION OF CALPROTECTIN IN INFLAMMATORY BOWEL DISEASE: FECAL AND SERUM LEVELS AND IMMONOHISTCHEMICAL LOCALIZATION Shuhei Fukunaga, Kotaro Kuwaki, Keiichi Mitsuyama, Hidetoshi Takedatsu, Shinichiro Yoshioka, Hiroshi Yamasaki, Ryosuke Yamauchi, Atsushi Mori, Osamu Tsuruta, Takuji Torimura The fecal calprotectin level is being increasingly used as a surrogate marker for disease activity in inflammatory bowel diseases. The primary objective of this study was to quantify the fecal calprotectin level using an enzyme-linked immunosorbent assay (ELISA) and to examine its correlations with endoscopic and clinical disease activity, laboratory parameters and the fecal hemoglobin (Hb) level. Additional objectives were to compare the fecal calprotectin ELISA results with those of a new, rapid, point-of-care test (POCT) for calprotectin and the serum calprotectin level and to detect calprotectin localization in the colon using immunohistochemistry. Methods: Overall, 113 patients with ulcerative colitis (UC) and 42 with Crohn's disease (CD) who were scheduled to undergo a colonoscopy were prospectively enrolled and scored both endoscopically and clinically. Feces and blood samples from both patients and normal controls were analyzed. These patients had received adequate medical treatment. The tissue distribution of calprotectin was investigated using immunohistochemistry. Results: The fecal calprotectin levels as measured using an ELISA were correlated with the endoscopic and clinical disease activities and other laboratory parameters, especially among the patients with UC. The performance of the fecal Hb level was close to that of the
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AGA Abstracts
AGA Abstracts
reference standard. MTR was evaluated as secondary and apparent diffusion coefficient (ADC) as exploratory objective. Methods: Informed consent was obtained from 51 stenotic CD patients eligible for resection surgery across 6 European centers in a prospective trial evaluating MRE for the detection of fibrosis in CD. Imaging was performed a median of two weeks (>90% <8 weeks) prior to surgery with no treatment changes in between. Local pathologists and radiologists annotated the location of 56 histological samples on the MRE scans, which was identified in the most stenosed region of corresponding resected specimens. An experienced pathologist centrally read the 56 samples using the Chiorean score.2 A single radiologist measured DGE, MTR, T2, ADC, and MaRIA index.1, 3 Correlation of histology and MRE metrics was performed using Pearson's R. Results: No association of fibrosis or inflammation with either DGE or MTR was found (fig 1). ADC was associated with fibrosis (R=-0.36, p=0.011). MaRIA score was correlated with inflammation (0.31, 0.031). Monitoring of image data quality by central reader resulted in >95% evaluable scans. Conclusions: In this prospective, multi-center study, DGE and MTR were not found to be in concordance with histological measure of fibrosis, in contrast to previously published findings. This may have been due to a spatial mismatch between histological tissue sample and imaging measurement region of interest, inconsistencies in the interval between imaging and surgery, the effects of histological preparation, or lack of granularity in histological scoring. However MaRIA scores were in good agreement with inflammation scoring, so it is possible that MRE metrics assist in the assessment of CD stenosis. Further development of histological scores and MRE metrics will inform upon MRE protocol development in CD. References: 1. Rimola J, et al. Am J Gastroenterol 2015. 2. Pazahr S, et al. MAGMA 2013. 3. Rimola, J, et al. Gut 2009.
TH, transmural healing; MH, mucosal healing; NH, no healing; SD, standard deviation
Mo1750 DISAGREEMENT AMONG GASTROENTEROLOGISTS IN THE ENDOSCOPIC EVALUATION USING THE MAYO ENDOSCOPIC SCORE AND THE RUTGEERTS POSTOPERATIVE SCORE Samuel Fernandes, João Pinto, Pedro M. da Costa, Luís Correia BACKGROUND: Endoscopic evaluation is an integral part in the evaluation of patients with Inflammatory bowel disease (IBD). Endoscopy is routinely used by most clinicians to evaluate disease severity and guide important clinical decisions. Therefore, variability in the interpretation of endoscopic findings amongst different gastroenterologists represents a problem of the upmost importance, which can severely impact the management of patients with IBD. OBJECTIVES: To study the inter-rater variability using the Mayo endoscopic subscore (MS) and Rutgeerts score (RS) amongst gastroenterologists. METHODS: Several gastroenterologists were invited to participate in an online survey including pictures and videos from patients with Crohn's disease (CD) and Ulcerative Colitis (UC), 20 questions. Participants were asked to rate the mucosal appearance in UC using the MS (0-3), and the neo-terminal ileum, anastomosis, and proximal colon in operated patients with CD using the RS (0-4). To assess the impact of clinical information on scoring, 2 identical questionnaires differing on the clinical information provided on 6 cases were used. In the second part, participants were able to consult the scores prior to answering the questions. The inter-rater concordance (IRC) was assessed using Krippendorff's alpha test. RESULTS: 58 gastroenterologists agreed to participate in the study. Nineteen (32.8%) stated to have more experience in IBD (seeing >10 patients/week), 50 (86.2%) performed endoscopy in IBD, and 52 (89.7%) routinely used the scores. The IRC for the MS and RS was 0.47 95%CI (0.41-0.54) and 0.33 95%CI (0.28-0.38). There was no influence of clinical information on the IRC for the MS (p=0.762) or the RS (p=0.147). Consultation of scores slightly improved the IRC for the MS [0.50 95%CI (0.42-0.58) vs 0.45 95%CI(0.38-0.51)], but not the RS [0.16 95%CI (0.10-0.21) vs 0.41 95%CI (0.35-0.46)]. The IRC for mucosal healing (MS≤1) and deep mucosal healing (MS=0) was 0.57 95%CI (0.40-0.72) and 0.89 95%CI (0.73-1). The IRC for postoperative recurrence (RS≥i2) was only 0.44 95%CI (0.24-0.62) and for severe recurrence (RS≥3) 0.54 95%CI (0.36-0.71). Considering the 18 participants stating to be more proficient in IBD (consults, endoscopy and scores), the IRC increased for the MS [0.54 95%CI (0.46-0.60)] and RS [0.42 95%CI (0.37-0.47)]. In this group, the IRC was also higher for mucosa healing (MS≤1) [0.62 95%CI (0.45-0.78)], deep mucosal healing (MS=0) [0.89 95%CI (0.75-1)], postoperative recurrence (RS≥2) [0.58 95%CI (0.39-0.76)], and severe postoperative recurrence (RS≥3) [0.59 95%CI (0.42-0.75)]. DISCUSSION: Our study confirms a high interrater disagreement amongst gastroenterologists using the MS and the RS, even amongst experienced physicians. Worryingly, there was only a moderate concordance for the most important outcomes- mucosal healing and postoperative recurrence.
Histological fibrosis (top) and inflammation scores (bottom) plotted against MRE parameters. ADC was associated with fibrosis. Inflammation was associated with MaRIA score.
Mo1749 TRANSMURAL HEALING IS BETTER THAN MUCOSAL HEALING IN CROHN'S DISEASE Samuel Fernandes, Rita Vale Rodrigues, Sónia Bernardo, João Cortez-Pinto, Isadora Rosa, Luís Correia, Cilénia Baldaia, Paula Moura-Santos, Ana R. Gonçalves, Ana Valente, João Pereira da Silva, António Dias Pereira, José Velosa BACKGROUND: Mucosal healing (MH) is currently accepted as the optimal target in Crohn's disease (CD), and is associated with improved long-term outcomes including reduced hospitalizations and surgery. However, even in patients with sustained MH, residual transmural inflammation may persist. The benefit of obtaining complete transmural healing (TH), have not been previously assessed. The aim of the study was to evaluate the long-term outcomes of TH in patients with CD. METHODS: This was a multicenter observational study including patients from a prospective database of Inflammatory bowel disease (Grupo de Estudos de Doença Inflamatória Intestinal). Patients with CD with a MRI-enterography (MRE) and colonoscopy performed in a 6-month interval were included. MRE was classified as active/ inactive based on the presence of abnormal bowel wall thickening, contrast enhancement, fat creeping, Comb sign, and complications (stricture, abscess or fistula). In non-operated patients, colonoscopy was classified as active/inactive based on the presence of ulceration. In operated patients, colonoscopy was classified as active/inactive if the Rutgeerts score was ≥i2. We defined 3 groups: TH (inactive MRE with inactive colonoscopy); MH (active MRE with inactive colonoscopy), No healing (NH) (active colonoscopy). We evaluated several outcomes at 1 year including the need for surgery, hospital admission, therapy escalation (immunomodulator, biologic or escalation of biologic), and a compound outcome including any of the former. Patients with inflammation restricted to the colon were excluded. RESULTS: A total of 214 patients [TH (n=33), MH (n=52), NH (n=129)], 91 (41.7%) previously operated, were included in the study. MRE and colonoscopy showed active inflammation in 162 (74.3%) and 132 patients (60.6%), respectively. At 12 months, patients with TH showed lower rates of hospital admission than patients with MH and NH (6.1% versus 17.3%, p=0.188 (n.s.) and 24.0%, p=0.014), therapy escalation (15.2% versus 36.5%, p= 0.027 and 54.3%, p<0.001), surgery (0% versus 11.5%, p=0.047 and 11.6%, p= 0.027), and any outcome (18.2% versus 44.2%, p=0.011 and 63.6%, p<0.001). Patients with TH showed longer times to surgery (p=0.045 and p=0.044 for MH and NH), therapy escalation (p=0.046 and p<0.001 for MH and NH), and to reach any endpoint (p=0.019 and p<0.001 for MH and NH). Increasing age at evaluation (OR 0.971 95%CI [0.951-0.992], p=0.006), MH (OR 0.384 95%CI [0.208-0.707], p=0.002), and TH (OR 0.336 95%CI [0.171-0.660, p=0.002] were independently associated with a lower likelihood of reaching the compound outcome. DISCUSSION: TH is associated with improved long-term outcomes in patients with CD, including lower risk of hospital admission, therapy escalation and surgery. Our data suggests that TH is a more suitable target than MH in CD.
Mo1751 DETECTION OF CALPROTECTIN IN INFLAMMATORY BOWEL DISEASE: FECAL AND SERUM LEVELS AND IMMONOHISTCHEMICAL LOCALIZATION Shuhei Fukunaga, Kotaro Kuwaki, Keiichi Mitsuyama, Hidetoshi Takedatsu, Shinichiro Yoshioka, Hiroshi Yamasaki, Ryosuke Yamauchi, Atsushi Mori, Osamu Tsuruta, Takuji Torimura The fecal calprotectin level is being increasingly used as a surrogate marker for disease activity in inflammatory bowel diseases. The primary objective of this study was to quantify the fecal calprotectin level using an enzyme-linked immunosorbent assay (ELISA) and to examine its correlations with endoscopic and clinical disease activity, laboratory parameters and the fecal hemoglobin (Hb) level. Additional objectives were to compare the fecal calprotectin ELISA results with those of a new, rapid, point-of-care test (POCT) for calprotectin and the serum calprotectin level and to detect calprotectin localization in the colon using immunohistochemistry. Methods: Overall, 113 patients with ulcerative colitis (UC) and 42 with Crohn's disease (CD) who were scheduled to undergo a colonoscopy were prospectively enrolled and scored both endoscopically and clinically. Feces and blood samples from both patients and normal controls were analyzed. These patients had received adequate medical treatment. The tissue distribution of calprotectin was investigated using immunohistochemistry. Results: The fecal calprotectin levels as measured using an ELISA were correlated with the endoscopic and clinical disease activities and other laboratory parameters, especially among the patients with UC. The performance of the fecal Hb level was close to that of the
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AGA Abstracts