- Email: [email protected]
Mo1205 Endoscopic Assessment of Mucosal Healing in Crohn's Disease by Novel iSCAN Endoscopic and Refined Histological Gradings
AGA Abstracts
knowledge this is among the first studies of esophageal microbiome in healthy, PPI-REE, and EoE children. Esophageal microbiome diversity and evenness was significantly different between healthy and EoE patients. PPI therapy modified the microbiome in richness and diversity towards that of healthy controls.. This suggests that changes in esophageal microbiome can be used to differentiate PPI-REE and EoE and could have implications on pathogenesis, evaluation and treatment of patients with EoE.
such as crypt architectural alteration (rs=0.49, p 0.0005), lamina propia mononuclear cellularity (rs= 0.3407, p 0.0191) and lamina propria eosinophilic infiltration (rs=0.3445, p 0.017). However, there was no significant correlation between iSCAN mucosal pattern and ECAP-CD scoring system. There was no significant correlation between iSCAN scoring system and CRP levels or HBI. Conclusion HD- iSCAN virtual electronic chromoendoscopy detected vascular abnormalities in a high proportion of patients with apparently healed mucosa. Subtle histological abnormalities can also be identified with a more comprehensive evaluation system of ECAP-CD. The clinical outcomes need prospective study over long term.
Mo1203 Mo1206
The Resection of Small Colorectal Polyps With a New Cold Resection Snare Is Safe and Highly Effective Jochen Weigt, Arne Kandulski, Peter Malfertheiner
Detection of Duodenal Papilla and Reading Time Using a New System of Small Bowel Capsule Endoscopy: Performance Comparison of SB2 and SB3 Akiko Shiotani, Keisuke Honda, Makiko Kawakami, Motoyasu Osawa, Manabu Ishii, Minoru Fujita, Hiroshi Matsumoto, Hiroaki Kusunoki, Jiro Hata, Ken Haruma
Background: Complete resection of colon adenomas is mandatory. Resection of small polyps with a forceps is easy and safe but yields a high rate of incomplete resections compared with snare resections. Small polyps may be resected mechanically using a snare without using diathermy. Aim: To evaluate a newly designed cold resection snare for the resection of small colorectal polyps. Methods: A specially designed snare (CrossSnare, Medwork, Germany) was used for cold resection of colorectal Polyps < 12 mm. Consecutive patients were prospectively enrolled. All resected specimens were carefully investigated by a histopathologist. No submucosal injection was performed before resection Results: We resected 78 polyps in 46 patients (33 male, 13 female; median age 63 yrs. range 31-85). In 14 patients more than one polyp was resected. In maximum 6 polyps were resected in session with the same snare. 33 polyps were located in the right colon and 45 polyps were located in the left colon. Polyp size was 4.8 mm ± 1.7 mm (2-12 mm). Histological assessment revealed 58 tubular adenomas 3 tubulo-villous adenomas and 2 serrated adenomas. None of them contained high grade IEN. The remaining 15 polyps were hyperplastic polyps. Of the 63 adenomas 58 were resected completely (92.1%) and only 5 were removed incompletely. The resection status of one adenoma was not assessable. No complications occurred. Conclusions: Cold resection of small colorectal adenomas with a the new cold snare is effective and safe and is an alternative for the resection using a biopsy forceps.
Background: PillCam® SB3 is a new capsule designed to provide an improved image quality and diagnostic accuracy due to creating more images with an Adaptive Frame Rate (AFR) of 2-6 fps. Moreover, the automatic mode of Rapid Reader® software ver.8.0 is thought to reduce the reading time and minimize the possibility of missing lesions. However, there is no published evidence that this claim has been proven objectively. Aim: We investigated the detection rate of duodenal papilla and reading time for CE images using the PillCam® SB3 system (Rapid reader ver. 8.0) compared with the previous SB2 system (ver. 6.5). The detection rate and reading time for CE images by two well-trained physicians and one expert nurse were compared. Results: We evaluated 30 procedures were performed using SB3 system and 30 using the SB2 system in which small bowel transit time was matched (i.e., mean small bowel transit time of SB3 and SB2 was 322 min and 326 min, respectively). The duodenal papilla was detected more frequently with the SB3 compared to the SB2 (36.7% vs 16.2%, p=0.02). Interobserver agreement was excellent (k = 0.82) using SB2 vs. good (k = 0.65) with SB3. There was no significant difference in the reading time (26 min vs 25 min) or the number of thumbnail images (22 vs 16) between SB3 and SB2. Conclusions: PillCam® SB3 detected duodenal papilla more frequently due to AFR without increasing reading time. Whether the increased number of frames will led to increased diagnostic accuracy for pathology remains to be tested.
Mo1204 Inhibition of MDR1 Gene Expression and Enhancing Cellular Uptake for Effective Colon Cancer Treatment Using Dual-Surface-Functionalized Nanoparticles Bo Xiao, Emilie Viennois, Yuan Zhao, Yuchen Zhang, Yunjin Jung, Mingzhen Zhang, Didier Merlin
Mo1207 Effect of Early Versus Late Azathioprine Treatment in Pediatric Ulcerative Colitis Giulia D'Arcangelo, Matteo Bramuzzo, Marco Gasparetto, Massimo Martinelli, Patrizia Alvisi, Maria Teresa Illiceto, Simona Valenti, Salvatore Pellegrino, Carlo Catassi, Serena Arrigo, Stefano Martelossi, Salvatore Cucchiara, Marina Aloi
Nanomedicine options for colon cancer therapy have been limited by the lack of suitable carriers capable of delivering sufficient drug into tumors to cause lethal toxicity. To circumvent this limitation, we fabricated a camptothecin (CPT)-loaded poly(lactic-co-glycolic acid) nanoparticle (NP) with dual-surface functionalization—Pluronic F127 and chitosan—for overcoming multi-drug resistance and enhancing tumor uptake. The resultant spherical NPsP/C had a desirable particle size (~268 nm), slightly positive zeta-potential, and the ability to efficiently down-regulate the expression of multidrug resistant gene 1 (MDR1). In vitro cytotoxicity tests revealed that the 24 and 48 h IC50 values of NPs-P/C1 were 2.03 and 0.67 μM, respectively, which were much lower than those for free CPT and other NPs. Interestingly, NPs-P/C1 showed the highest cellular uptake efficiency (approximately 85.5%) among the different drug formulations. Most importantly, treatment of colon tumor-bearing mice with various drug formulations confirmed that the introduction of Pluronic F127 and chitosan to the NP surface significantly enhanced the therapeutic efficacy of CPT, induced tumor cell apoptosis, and reduced systemic toxicity. Collectively, these findings suggest that our one-step-fabricated, dual-surface-functionalized NPs may hold promise as a readily scalable and effective drug carrier with clinical potential in colon cancer therapy.
Background and aim: Thiopurines, 6-mercaptopurine and azathioprine (AZA), are the mainstay in maintenance treatment for pediatric ulcerative colitis (UC). We aimed at describing the efficacy of AZA in newly diagnosed pediatric UC, comparing the outcomes of "early" (0-6 months) versus "late" (6-12 months) initiation of therapy. Methods: Data from all children with UC, treated with AZA within 12 months of diagnosis and included in the SIGENP prospective, multicenter registry, were included. Corticosteroid (CS) free remission at 12 months was the primary outcome evaluated. Patients were also compared for mucosal healing, need for treatment escalation, therapy-related adverse events and need for surgery, based on the timing of AZA initiation. Results: Of 401 children with a diagnosis of UC, 166 were treated with AZA within 1 year of diagnosis. Seventy-one patients were excluded because of a follow-up shorter than 1 year, thus 95 children were included for efficacy analyses (mean age 10.7±3.8 years, 59% females). Fifty-four patients (57%) started AZA between 0-6 months (early), 41 (43%) between 6-12 months (late). CS-free remission at 1 year was achieved by 27 (51%) of the "early" patients, compared with 24 (61.5%) of the "late" ones (p=0.39). Mucosal healing occurred in 26 (39%) of the 66 patients for whom data on mucosal inflammation at 1 year were available; no difference was found between the two groups (32% "early" versus 45% "late"; p=0.45). Serious adverse events occurred in 3 patients (2 fungal pneumonia, 1 pancreatitis), 2 in the "early" and 1 in the "late" group. Overall, mild side effects were recorded in 16 patients (17%; 5 leucopenia, 11 pancreatic enzyme elevation):10 in the "early" and 6 in the "late" group (p=0.78), 3 requiring AZA discontinuation.No difference was found for the need of treatment escalation, use of infliximab over time and rate of surgery. Conclusions: Introduction of AZA within 6 months of diagnosis is not more effective than later treatment to achieve CS-free remission in pediatric UC. The rate of mucosal healing is not related to the timing of AZA initiation. Serious adverse events under AZA therapy are uncommon.
Mo1205 Endoscopic Assessment of Mucosal Healing in Crohn's Disease by Novel iSCAN Endoscopic and Refined Histological Gradings Marietta Iacucci, Miriam Fort Gasia, Remo Panaccione, Gilaad Kaplan, Subrata Ghosh, Xianyong Gui Background Endoscopic assessment of mucosal healing (MH) is considered an important therapeutic endpoint in Crohn's disease. High definition(HD) iSCAN virtual electronic chromoendoscopy may detect mucosal and vascular details that are not obvious on high definition white light endoscopy (WLE). More refined histologic and HD- iSCAN endoscopic criteria may characterize and better describe mucosal healing in Crohn's disease patients. Patients& methods 47 consecutive patients (24 female, median age 44.5, range 22-70) with inactive (Harvey-Bradshaw index, HBI ≤4) disease were studied using high definition-iSCAN (EC3490Fi; Pentax Tokyo). SES-CD endoscopic index of severity score was assigned to patients according WLE appearance. MH pattern on iSCAN was graded as 1=normal, 2=mosaic pattern, 3=grooves. The vascular pattern was graded as 1= normal, 2=spiral drop-out vessels, 3=crowded tortuous vessels. A new histological scoring system that assesses all changes seen in IBD was developed for a detailed and comprehensive evaluation. This system (ECAP-CD system) was designed to reflect all histologic changes in IBD categorized as 1) Extent of inflammation, 2) Chronicity (crypt architectural alteration and Paneth cell metaplasia) 3) Activity (surface epithelium changes, neutrophilic cryptitis, crypt abscess, crypt destruction, lamina propria mononuclear cellularity, lamina propria neutrophil infiltration, and basal plasmacytosis), and 4) Plus additional findings, including eosinophilia, lymphoid follicles/ aggregates and granuloma. iSCAN scoring system was correlated with HBI, CRP levels, endoscopic SES-CD, and histologic ECAP-CD scoring system by using non-parametric Spearman correlation coefficient. ResultsOf 47 patients with SES-CD endoscopic score of 0, 62% had abnormal vascular pattern and 57.5% had abnormal mucosal pattern at HDiSCAN . Only five out of 47 patients had a completely normal histological assessment under the ECAP-CD scoring system. There was significant correlation between the iSCAN vascular pattern and the total ECAP-CD scoring system (rs=0.348, p 0.0164), especially in features
AGA Abstracts
Mo1208 Effect of Adalimumab on Clinical Laboratory Parameters in Pediatric Crohn's Disease Patients From IMAgINE 1 Jeffrey S. Hyams, Joel R. Rosh, James Markowitz, Jaroslaw Kierkus, Marla Dubinsky, Dan Turner, William A. Faubion, Samantha Eichner, Andreas Lazar, Yao Li, Roopal Thakkar BACKGROUND. Adalimumab (ADA) was shown to be effective for inducing and maintaining clinical remission in children with moderately to severely active Crohn's disease (CD) in IMAgINE 1.1 Changes in laboratory values indicative of systemic inflammation were evaluated. METHODS. Patients (pts), 6-17 years-old, with baseline (BL) Paediatric CD Activity Index >30 received open-label induction ADA at weeks (wks) 0/2 by body weight (<40 kg, 80/40 mg; ≥40 kg, 160/80 mg). At wk 4, pts were randomized to double-blind (DB) higher-dose (HD) ADA (<40 kg, 20 mg every other wk [eow]; ≥40 kg, 40 mg eow) or lower-dose (LD) ADA (<40 kg, 10 mg eow; ≥40 kg, 20 mg eow) for 48 wks. The proportion of pts with abnormal values at BL, who later achieved normal values at wk 52 were evaluated. Albumin levels of >3.4 g/dL, platelet counts of <500x109 platelets/L, and CRP levels of <1 mg/dL were considered normal. Mean change in hemoglobin from BL to wk 52 was also assessed. Last observation carried forward (LOCF) was used for missing
S-638
knowledge this is among the first studies of esophageal microbiome in healthy, PPI-REE, and EoE children. Esophageal microbiome diversity and evenness was significantly different between healthy and EoE patients. PPI therapy modified the microbiome in richness and diversity towards that of healthy controls.. This suggests that changes in esophageal microbiome can be used to differentiate PPI-REE and EoE and could have implications on pathogenesis, evaluation and treatment of patients with EoE.
such as crypt architectural alteration (rs=0.49, p 0.0005), lamina propia mononuclear cellularity (rs= 0.3407, p 0.0191) and lamina propria eosinophilic infiltration (rs=0.3445, p 0.017). However, there was no significant correlation between iSCAN mucosal pattern and ECAP-CD scoring system. There was no significant correlation between iSCAN scoring system and CRP levels or HBI. Conclusion HD- iSCAN virtual electronic chromoendoscopy detected vascular abnormalities in a high proportion of patients with apparently healed mucosa. Subtle histological abnormalities can also be identified with a more comprehensive evaluation system of ECAP-CD. The clinical outcomes need prospective study over long term.
Mo1203 Mo1206
The Resection of Small Colorectal Polyps With a New Cold Resection Snare Is Safe and Highly Effective Jochen Weigt, Arne Kandulski, Peter Malfertheiner
Detection of Duodenal Papilla and Reading Time Using a New System of Small Bowel Capsule Endoscopy: Performance Comparison of SB2 and SB3 Akiko Shiotani, Keisuke Honda, Makiko Kawakami, Motoyasu Osawa, Manabu Ishii, Minoru Fujita, Hiroshi Matsumoto, Hiroaki Kusunoki, Jiro Hata, Ken Haruma
Background: Complete resection of colon adenomas is mandatory. Resection of small polyps with a forceps is easy and safe but yields a high rate of incomplete resections compared with snare resections. Small polyps may be resected mechanically using a snare without using diathermy. Aim: To evaluate a newly designed cold resection snare for the resection of small colorectal polyps. Methods: A specially designed snare (CrossSnare, Medwork, Germany) was used for cold resection of colorectal Polyps < 12 mm. Consecutive patients were prospectively enrolled. All resected specimens were carefully investigated by a histopathologist. No submucosal injection was performed before resection Results: We resected 78 polyps in 46 patients (33 male, 13 female; median age 63 yrs. range 31-85). In 14 patients more than one polyp was resected. In maximum 6 polyps were resected in session with the same snare. 33 polyps were located in the right colon and 45 polyps were located in the left colon. Polyp size was 4.8 mm ± 1.7 mm (2-12 mm). Histological assessment revealed 58 tubular adenomas 3 tubulo-villous adenomas and 2 serrated adenomas. None of them contained high grade IEN. The remaining 15 polyps were hyperplastic polyps. Of the 63 adenomas 58 were resected completely (92.1%) and only 5 were removed incompletely. The resection status of one adenoma was not assessable. No complications occurred. Conclusions: Cold resection of small colorectal adenomas with a the new cold snare is effective and safe and is an alternative for the resection using a biopsy forceps.
Background: PillCam® SB3 is a new capsule designed to provide an improved image quality and diagnostic accuracy due to creating more images with an Adaptive Frame Rate (AFR) of 2-6 fps. Moreover, the automatic mode of Rapid Reader® software ver.8.0 is thought to reduce the reading time and minimize the possibility of missing lesions. However, there is no published evidence that this claim has been proven objectively. Aim: We investigated the detection rate of duodenal papilla and reading time for CE images using the PillCam® SB3 system (Rapid reader ver. 8.0) compared with the previous SB2 system (ver. 6.5). The detection rate and reading time for CE images by two well-trained physicians and one expert nurse were compared. Results: We evaluated 30 procedures were performed using SB3 system and 30 using the SB2 system in which small bowel transit time was matched (i.e., mean small bowel transit time of SB3 and SB2 was 322 min and 326 min, respectively). The duodenal papilla was detected more frequently with the SB3 compared to the SB2 (36.7% vs 16.2%, p=0.02). Interobserver agreement was excellent (k = 0.82) using SB2 vs. good (k = 0.65) with SB3. There was no significant difference in the reading time (26 min vs 25 min) or the number of thumbnail images (22 vs 16) between SB3 and SB2. Conclusions: PillCam® SB3 detected duodenal papilla more frequently due to AFR without increasing reading time. Whether the increased number of frames will led to increased diagnostic accuracy for pathology remains to be tested.
Mo1204 Inhibition of MDR1 Gene Expression and Enhancing Cellular Uptake for Effective Colon Cancer Treatment Using Dual-Surface-Functionalized Nanoparticles Bo Xiao, Emilie Viennois, Yuan Zhao, Yuchen Zhang, Yunjin Jung, Mingzhen Zhang, Didier Merlin
Mo1207 Effect of Early Versus Late Azathioprine Treatment in Pediatric Ulcerative Colitis Giulia D'Arcangelo, Matteo Bramuzzo, Marco Gasparetto, Massimo Martinelli, Patrizia Alvisi, Maria Teresa Illiceto, Simona Valenti, Salvatore Pellegrino, Carlo Catassi, Serena Arrigo, Stefano Martelossi, Salvatore Cucchiara, Marina Aloi
Nanomedicine options for colon cancer therapy have been limited by the lack of suitable carriers capable of delivering sufficient drug into tumors to cause lethal toxicity. To circumvent this limitation, we fabricated a camptothecin (CPT)-loaded poly(lactic-co-glycolic acid) nanoparticle (NP) with dual-surface functionalization—Pluronic F127 and chitosan—for overcoming multi-drug resistance and enhancing tumor uptake. The resultant spherical NPsP/C had a desirable particle size (~268 nm), slightly positive zeta-potential, and the ability to efficiently down-regulate the expression of multidrug resistant gene 1 (MDR1). In vitro cytotoxicity tests revealed that the 24 and 48 h IC50 values of NPs-P/C1 were 2.03 and 0.67 μM, respectively, which were much lower than those for free CPT and other NPs. Interestingly, NPs-P/C1 showed the highest cellular uptake efficiency (approximately 85.5%) among the different drug formulations. Most importantly, treatment of colon tumor-bearing mice with various drug formulations confirmed that the introduction of Pluronic F127 and chitosan to the NP surface significantly enhanced the therapeutic efficacy of CPT, induced tumor cell apoptosis, and reduced systemic toxicity. Collectively, these findings suggest that our one-step-fabricated, dual-surface-functionalized NPs may hold promise as a readily scalable and effective drug carrier with clinical potential in colon cancer therapy.
Background and aim: Thiopurines, 6-mercaptopurine and azathioprine (AZA), are the mainstay in maintenance treatment for pediatric ulcerative colitis (UC). We aimed at describing the efficacy of AZA in newly diagnosed pediatric UC, comparing the outcomes of "early" (0-6 months) versus "late" (6-12 months) initiation of therapy. Methods: Data from all children with UC, treated with AZA within 12 months of diagnosis and included in the SIGENP prospective, multicenter registry, were included. Corticosteroid (CS) free remission at 12 months was the primary outcome evaluated. Patients were also compared for mucosal healing, need for treatment escalation, therapy-related adverse events and need for surgery, based on the timing of AZA initiation. Results: Of 401 children with a diagnosis of UC, 166 were treated with AZA within 1 year of diagnosis. Seventy-one patients were excluded because of a follow-up shorter than 1 year, thus 95 children were included for efficacy analyses (mean age 10.7±3.8 years, 59% females). Fifty-four patients (57%) started AZA between 0-6 months (early), 41 (43%) between 6-12 months (late). CS-free remission at 1 year was achieved by 27 (51%) of the "early" patients, compared with 24 (61.5%) of the "late" ones (p=0.39). Mucosal healing occurred in 26 (39%) of the 66 patients for whom data on mucosal inflammation at 1 year were available; no difference was found between the two groups (32% "early" versus 45% "late"; p=0.45). Serious adverse events occurred in 3 patients (2 fungal pneumonia, 1 pancreatitis), 2 in the "early" and 1 in the "late" group. Overall, mild side effects were recorded in 16 patients (17%; 5 leucopenia, 11 pancreatic enzyme elevation):10 in the "early" and 6 in the "late" group (p=0.78), 3 requiring AZA discontinuation.No difference was found for the need of treatment escalation, use of infliximab over time and rate of surgery. Conclusions: Introduction of AZA within 6 months of diagnosis is not more effective than later treatment to achieve CS-free remission in pediatric UC. The rate of mucosal healing is not related to the timing of AZA initiation. Serious adverse events under AZA therapy are uncommon.
Mo1205 Endoscopic Assessment of Mucosal Healing in Crohn's Disease by Novel iSCAN Endoscopic and Refined Histological Gradings Marietta Iacucci, Miriam Fort Gasia, Remo Panaccione, Gilaad Kaplan, Subrata Ghosh, Xianyong Gui Background Endoscopic assessment of mucosal healing (MH) is considered an important therapeutic endpoint in Crohn's disease. High definition(HD) iSCAN virtual electronic chromoendoscopy may detect mucosal and vascular details that are not obvious on high definition white light endoscopy (WLE). More refined histologic and HD- iSCAN endoscopic criteria may characterize and better describe mucosal healing in Crohn's disease patients. Patients& methods 47 consecutive patients (24 female, median age 44.5, range 22-70) with inactive (Harvey-Bradshaw index, HBI ≤4) disease were studied using high definition-iSCAN (EC3490Fi; Pentax Tokyo). SES-CD endoscopic index of severity score was assigned to patients according WLE appearance. MH pattern on iSCAN was graded as 1=normal, 2=mosaic pattern, 3=grooves. The vascular pattern was graded as 1= normal, 2=spiral drop-out vessels, 3=crowded tortuous vessels. A new histological scoring system that assesses all changes seen in IBD was developed for a detailed and comprehensive evaluation. This system (ECAP-CD system) was designed to reflect all histologic changes in IBD categorized as 1) Extent of inflammation, 2) Chronicity (crypt architectural alteration and Paneth cell metaplasia) 3) Activity (surface epithelium changes, neutrophilic cryptitis, crypt abscess, crypt destruction, lamina propria mononuclear cellularity, lamina propria neutrophil infiltration, and basal plasmacytosis), and 4) Plus additional findings, including eosinophilia, lymphoid follicles/ aggregates and granuloma. iSCAN scoring system was correlated with HBI, CRP levels, endoscopic SES-CD, and histologic ECAP-CD scoring system by using non-parametric Spearman correlation coefficient. ResultsOf 47 patients with SES-CD endoscopic score of 0, 62% had abnormal vascular pattern and 57.5% had abnormal mucosal pattern at HDiSCAN . Only five out of 47 patients had a completely normal histological assessment under the ECAP-CD scoring system. There was significant correlation between the iSCAN vascular pattern and the total ECAP-CD scoring system (rs=0.348, p 0.0164), especially in features
AGA Abstracts
Mo1208 Effect of Adalimumab on Clinical Laboratory Parameters in Pediatric Crohn's Disease Patients From IMAgINE 1 Jeffrey S. Hyams, Joel R. Rosh, James Markowitz, Jaroslaw Kierkus, Marla Dubinsky, Dan Turner, William A. Faubion, Samantha Eichner, Andreas Lazar, Yao Li, Roopal Thakkar BACKGROUND. Adalimumab (ADA) was shown to be effective for inducing and maintaining clinical remission in children with moderately to severely active Crohn's disease (CD) in IMAgINE 1.1 Changes in laboratory values indicative of systemic inflammation were evaluated. METHODS. Patients (pts), 6-17 years-old, with baseline (BL) Paediatric CD Activity Index >30 received open-label induction ADA at weeks (wks) 0/2 by body weight (<40 kg, 80/40 mg; ≥40 kg, 160/80 mg). At wk 4, pts were randomized to double-blind (DB) higher-dose (HD) ADA (<40 kg, 20 mg every other wk [eow]; ≥40 kg, 40 mg eow) or lower-dose (LD) ADA (<40 kg, 10 mg eow; ≥40 kg, 20 mg eow) for 48 wks. The proportion of pts with abnormal values at BL, who later achieved normal values at wk 52 were evaluated. Albumin levels of >3.4 g/dL, platelet counts of <500x109 platelets/L, and CRP levels of <1 mg/dL were considered normal. Mean change in hemoglobin from BL to wk 52 was also assessed. Last observation carried forward (LOCF) was used for missing
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