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AGA Abstracts 211 Incomplete Colonoscopy: Significant Findings in a Mixed Referral Population During Follow Up Maarten Neerincx, Jochim S. Terhaar sive Droste, Mirre Räkers, Ruud J. Loffeld, Chris J. Mulder, René W. van der Hulst Background: In literature in 87-98% of colonoscopies, caecal intubation is inadequate. However, the magnitude of missed significant lesions in the unobserved part of the colon remains unknown and the efforts made by physicians to visualize the remaining part of the colon are still elusive.Aim: We evaluated 1)the reasons for failure, 2)the diagnostic yield after a second investigation of the large bowel and 3)the highest diagnostic accuracy adjusted for the various procedures.Methods: In a population-based cohort study in the Amsterdam area, data of all colonoscopies performed during a three months period were analyzed to identify incomplete colonoscopies. Incompleteness was defined as inability to intubate the caecum. Secondary examinations to visualize the unobserved part of the colon were assessed until 18 months after the index colonoscopy. Follow up examinations included: repeated colonoscopy, CT colonography, barium enema, CT abdomen and surgical interventions involving the colorectum.Results: Of 3149 procedures, 289 were incomplete (9.2%). Incom- plete colonoscopy was predominant in females (OR 1.39; 95% CI: 1.09-1.79) and in proced- ures without conscious sedation (OR 2.65; 95% CI: 2.02-3.47). Reasons for failure included dolichocolon (19%), discomfort (13%), obstructing tumour (13%), suspected adhesions (13%), stenosis/diverticulosis (13%), insufficient preparation (12%) and severe inflammation (2%). Follow up examinations were performed in 55% of the patients. The remaining 45% consisted mainly of patients with IBS related complaints (14%), rectal blood loss (9%) and patients with full visualization of the colon <1 year before (10%). With follow up examination, colorectal carcinoma was diagnosed in 16 patients (6%), advanced adenoma in 3 patients (1%) and other polyps in 6 patients (2%). In 23 patients (8%), other colon pathology was diagnosed (i.e. diverticulosis, inflammatory bowel disease, fistula).Discussion: In 22/289 patients, neoplasia was found that was missed by incomplete colonoscopy. Surgical interven- tion and repeated colonoscopy resulted in the highest secondary diagnostic yield. Therefore, in a mixed referral population incomplete colonoscopy should be followed by either a repeated colonoscopy/additional imaging and if necessary surgical intervention. Follow-up procedure and diagnostic yield 212 Impact of a Novel Patient Educational Booklet On the Quality of Colonoscopy Preparation in Colorectal Cancer Screening Brennan M. Spiegel, Michael Y. Chan, Jennifer Talley, Hartley Cohen Background: Colonoscopy is the gold standard for colorectal cancer (CRC) screening because it can find and remove pre-malignant polyps and reduce subsequent CRC. Healthcare systems in the U.S. and abroad have committed extensive resources to ensuring use of screening colonoscopy. Yet 20-60% of patients presenting to colonoscopy have inadequate bowel preparation across healthcare settings. Achievement of key quality indicators for colonoscopy, including benchmark polyp detection rates and complete exam rates, depends on the quality of bowel preparation. Patients with poor preps have fewer polyps found, more incomplete exams, and higher costs of care. This suggests that improving quality will require improving patient preparation. We therefore sought to develop and test an educational booklet designed to improve bowel preparation quality in patients undergoing colonoscopy in a large VA Healthcare Network. Methods: We first performed cognitive interviews in 20 patients, 10 GIs, and 5 GI nurses to identify patient knowledge, attitude, and belief (KAB) deficits hypothesized to drive inadequate colonoscopy preparation. We then created a novel educa- tional booklet, based on the Health Beliefs Model, aimed at addressing KAB deficits to improve desired preparatory behaviors. In concert with a psychometrician and health literacy expert, we developed a color booklet containing text and visual elements designed to address modifiable KAB domains. The booklet was iteratively revised with feedback from 60 patients. We then performed a controlled before and after study to compare bowel preparation quality, measured on a standard 7-point Likert scale (>=6 is “good”), in patients undergoing screening colonoscopy during 2 consecutive months: 1 without and 1 with the booklet. Patients in both time periods received standard pharmacy instructions. We performed chi-squared to compare the proportion achieving a “good” prep between groups, and logistic regression to measure the impact of the booklet on prep quality, adjusting for age, sex, race, BMI, and the type of prep prescribed. Results: 61% vs. 45% of patients had a good prep in the booklet (N=63) and control (N=93) groups, respectively (p=0.04). In multivariable regression analysis, receipt of the booklet increased the odds of a good prep by 1.9 times (95% CI= 1.1-3.4). Conclusions: Provision of a novel educational booklet improved bowel preparation quality in patients undergoing screening colonoscopy, independent of the type of prep received. This simple intervention improved prep quality by addressing and modifying KAB deficits that drive quality over and above the specific purgative prescribed. A-40 AGA Abstracts 213 Ethnicity Is a Critical Factor Predicting Non-Attendance to Scheduled Colonoscopy: Hispanics and Native Americans Have Alarmingly High Non- Attendance Rates Nitesh B. Vachhani, Wen-Huan S. Ho, Mohamed O. Othman, Thomas Y. Ma Background: Screening colonoscopy detects precancerous polyps and prevents the develop- ment of colorectal cancer (CRC). Widespread colonoscopy screening programs appear to be a key factor contributing to the overall decline of CRC in the USA. Despite the overall decline in the incidence of CRC, there has been an alarming increase in incidence among Hispanics (Hisp) and Native Americans (NA). We hypothesize that non-compliance to scheduled colonoscopies could be an important factor contributing to the divergent increase in CRC among Hisp and NA. The unique ethnic diversity of New Mexico population, consisting of 45% non-Hisp Whites (NHW), 42% Hisp, and 10% NA, offers an ideal setting to assess ethnic differences in compliance rates to colonoscopy. The major aim of this study was to determine the factors that were associated with non-attendance for scheduled colonoscopy. Methods: We performed a retrospective analysis of 1147 consecutive scheduled colonoscopies at a large open access tertiary center. Demographic data and reasons for non-attendance were collected by chart review and telephone interviews. The strength of associations was assessed using a step-wise logistic regression analysis. Results: Among 1147 patients scheduled for colonoscopy, 38% were NHW, 42% were Hisp, and 7% were NA. The overall nonattendance rate was 28.5%. The non-attendance rate for NHW was 21%. The attendance rate for Hisp was only about ½ of NHW [OR: 0.517 (CI= 0.380-0.703)] and NA was about ¼ of NHW [OR: 0.272 (CI = 0.165-0.448), indicating a 2-4 times higher non-compliance rate among Hisp and NA. Other factors that were significantly associated with higher non-attendance included marital status, insurance status, and age. Single patients were more likely to miss their appointment than married patients (p= 0.0012). Patients with public funded insurance had higher non-attendance rate than the privately insured (p<0.0001). Younger patients (< 50) had higher non-attendance rate than older patients (50) (p = 0.038). Of clinical importance was that the nonattendance rate for patients having alarm features (guiaiac (+) stools or change in bowel movements) appeared to be similar to those referred for elective screening purposes. Conclusion: Our results indicate for the first time that the non-attendance rate for scheduled colonoscopy is much higher (2-4 fold) among Hisp and NA than NHW. The higher non-attendance rate among Hisp and NA could explain the continued rise in CRC among these ethnic groups. Thus, future strategies that improve the compliance rate for colonoscopy in these ethnic groups could be crucial in reducing the incidence of CRC in Hisp and NA. 214 Expression of hPepT1 Aggravates Intestinal Inflammation Guillaume Dalmasso, Hang Thi Thu Nguyen, Yutao Yan, Mauricio Rojas, Shanthi V. Sitaraman, Didier Merlin Background & aims: The human di-tripeptide transporter hPepT1 plays a key role in mediating immune response by transporting bacterial peptides. hPepT1 is not expressed in the colon but is induced in chronic inflamed colon, such as inflammatory bowel disease (IBD). Here we aimed at investigating the role of hPepT1 in IBD. Methods: To obtain strong and ubiquitous transgene expression in mice, we constructed a β-actin promoter-hPepT1 expression vector. hPepT1 expression was assessed by immunohistochemistry, RT-PCR and Western blot in several tissues. Transport activity of PepT1 in mouse colon was assessed by measuring PepT1-mediated lysine-proline-valine (KPV) uptake in colonic membrane vesicles. Colitis in wild type (WT) and hPepT1 transgenic mice (hPepT1 +/+ ) was induced by 3% DSS or TNBS. Inflammation was assessed by MPO activity, an indicator of neutrophils infiltration, and by quantification of pro-inflammatory cytokines in mouse colon using real- time RT-PCR. For bone marrow transplants, mice were irradiated and received bone marrow (5 x 10 6 cells in 50μl were transplanted retroorbitally). Results: The macroscopic examination of body cavities, organs and tissues of hPepT1 +/+ mice did not show any abnormal phenotype. Other tissues, such as skin, heart, lungs, thymus, exocrine pancreas, kidney, spinal cord, or ganglia of peripheral nervous system were unremarkable at the microscopic examination. Western blot analysis showed a strong ubiquitous hPepT1 expression in every tissue of hPepT1 +/+ mice. Colonic membrane vesicles from these mice exhibited a strong hPepT1 expression and higher KPV uptake compared to WT mice, indicating that colonic hPepT1 is functional. DSS and TNBS treatments induced more weight loss and neutrophil infiltration into colonic mucosa in hPepT1 +/+ mice compared to WT mice. Furthermore, hPepT1 +/+ mice exhibited higher mortality than WT mice during the recovery phase after DSS treatment. Remarkably, DSS and TNBS induced drastically increased expression levels of pro-inflammat- ory cytokines (IL-1β, IL-6, IL-12, IFN-γ and TNF-α) in hPepT1 +/+ mouse colon compared to WT. Interestingly, DSS-induced IL-1β and IL-6 expressions in hPepT1 +/+ myeloid cell- received WT mice were significantly reduced compared to WT myeloid cell-received hPepT1 mice. These data suggest that hPepT1 expression in epithelial cells plays a key role in intestinal inflammation. Conclusions: Here we developed an In Vivo model to study the pathophysiological relevance of hPepT1 over-expression in IBD. Our data using this mouse model demonstrate that expression of colonic hPepT1 observed during IBD may increase the severity of the colitis. 215 Protective Role of EGFR in IL-10-Mediated Colitis Philip E. Dubé, Kay Washington, D. Brent Polk Epidermal growth factor receptor (EGFR) enhances intestinal epithelial homeostasis, restitu- tion and repair. Loss of EGFR ligands or inactivating EGFR mutations sensitize mice to acute colitis. We tested whether EGFR-inactivating mutations (EGFR wa2/wa2 or EGFR wa5 ) accelerate disease progression in the interleukin-10 knockout (IL-10 -/- ) chronic colitis model. METHODS: IL-10 -/- mice with EGFR wa2/wa2 or EGFR wa5 mutations (collectively IL-10 -/- EGFR wa ) were compared to IL-10 -/- mice (all C57Bl/6 from the same colony). Controls were wildtype, EGFR wa2/wa2 and EGFR wa5 mice. Colonoscopy was performed between 6-28wk of

214 Expression of hPepT1 Aggravates Intestinal Inflammation

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Incomplete Colonoscopy: Significant Findings in a Mixed Referral PopulationDuring Follow UpMaarten Neerincx, Jochim S. Terhaar sive Droste, Mirre Räkers, Ruud J. Loffeld, Chris J.Mulder, René W. van der Hulst

Background: In literature in 87-98% of colonoscopies, caecal intubation is inadequate.However, the magnitude of missed significant lesions in the unobserved part of the colonremains unknown and the efforts made by physicians to visualize the remaining part of thecolon are still elusive.Aim: We evaluated 1)the reasons for failure, 2)the diagnostic yieldafter a second investigation of the large bowel and 3)the highest diagnostic accuracy adjustedfor the various procedures.Methods: In a population-based cohort study in the Amsterdamarea, data of all colonoscopies performed during a three months period were analyzed toidentify incomplete colonoscopies. Incompleteness was defined as inability to intubate thecaecum. Secondary examinations to visualize the unobserved part of the colon were assesseduntil 18 months after the index colonoscopy. Follow up examinations included: repeatedcolonoscopy, CT colonography, barium enema, CT abdomen and surgical interventionsinvolving the colorectum.Results: Of 3149 procedures, 289 were incomplete (9.2%). Incom-plete colonoscopy was predominant in females (OR 1.39; 95% CI: 1.09-1.79) and in proced-ures without conscious sedation (OR 2.65; 95% CI: 2.02-3.47). Reasons for failure includeddolichocolon (19%), discomfort (13%), obstructing tumour (13%), suspected adhesions(13%), stenosis/diverticulosis (13%), insufficient preparation (12%) and severe inflammation(2%). Follow up examinations were performed in 55% of the patients. The remaining 45%consisted mainly of patients with IBS related complaints (14%), rectal blood loss (9%) andpatients with full visualization of the colon <1 year before (10%).With follow up examination,colorectal carcinoma was diagnosed in 16 patients (6%), advanced adenoma in 3 patients(1%) and other polyps in 6 patients (2%). In 23 patients (8%), other colon pathology wasdiagnosed (i.e. diverticulosis, inflammatory bowel disease, fistula).Discussion: In 22/289patients, neoplasia was found that was missed by incomplete colonoscopy. Surgical interven-tion and repeated colonoscopy resulted in the highest secondary diagnostic yield. Therefore,in a mixed referral population incomplete colonoscopy should be followed by either arepeated colonoscopy/additional imaging and if necessary surgical intervention.Follow-up procedure and diagnostic yield

212

Impact of a Novel Patient Educational Booklet On the Quality of ColonoscopyPreparation in Colorectal Cancer ScreeningBrennan M. Spiegel, Michael Y. Chan, Jennifer Talley, Hartley Cohen

Background: Colonoscopy is the gold standard for colorectal cancer (CRC) screening becauseit can find and remove pre-malignant polyps and reduce subsequent CRC. Healthcare systemsin the U.S. and abroad have committed extensive resources to ensuring use of screeningcolonoscopy. Yet 20-60% of patients presenting to colonoscopy have inadequate bowelpreparation across healthcare settings. Achievement of key quality indicators for colonoscopy,including benchmark polyp detection rates and complete exam rates, depends on the qualityof bowel preparation. Patients with poor preps have fewer polyps found, more incompleteexams, and higher costs of care. This suggests that improving quality will require improvingpatient preparation. We therefore sought to develop and test an educational booklet designedto improve bowel preparation quality in patients undergoing colonoscopy in a large VAHealthcare Network. Methods: We first performed cognitive interviews in 20 patients, 10GIs, and 5 GI nurses to identify patient knowledge, attitude, and belief (KAB) deficitshypothesized to drive inadequate colonoscopy preparation. We then created a novel educa-tional booklet, based on the Health Beliefs Model, aimed at addressing KAB deficits toimprove desired preparatory behaviors. In concert with a psychometrician and health literacyexpert, we developed a color booklet containing text and visual elements designed to addressmodifiable KAB domains. The booklet was iteratively revised with feedback from 60 patients.We then performed a controlled before and after study to compare bowel preparation quality,measured on a standard 7-point Likert scale (>=6 is “good”), in patients undergoing screeningcolonoscopy during 2 consecutive months: 1 without and 1 with the booklet. Patients inboth time periods received standard pharmacy instructions. We performed chi-squared tocompare the proportion achieving a “good” prep between groups, and logistic regression tomeasure the impact of the booklet on prep quality, adjusting for age, sex, race, BMI, andthe type of prep prescribed. Results: 61% vs. 45% of patients had a good prep in thebooklet (N=63) and control (N=93) groups, respectively (p=0.04). In multivariable regressionanalysis, receipt of the booklet increased the odds of a good prep by 1.9 times (95% CI=1.1-3.4). Conclusions: Provision of a novel educational booklet improved bowel preparationquality in patients undergoing screening colonoscopy, independent of the type of prepreceived. This simple intervention improved prep quality by addressing and modifying KABdeficits that drive quality over and above the specific purgative prescribed.

A-40AGA Abstracts

213

Ethnicity Is a Critical Factor Predicting Non-Attendance to ScheduledColonoscopy: Hispanics and Native Americans Have Alarmingly High Non-Attendance RatesNitesh B. Vachhani, Wen-Huan S. Ho, Mohamed O. Othman, Thomas Y. Ma

Background: Screening colonoscopy detects precancerous polyps and prevents the develop-ment of colorectal cancer (CRC). Widespread colonoscopy screening programs appear tobe a key factor contributing to the overall decline of CRC in the USA. Despite the overalldecline in the incidence of CRC, there has been an alarming increase in incidence amongHispanics (Hisp) and Native Americans (NA). We hypothesize that non-compliance toscheduled colonoscopies could be an important factor contributing to the divergent increasein CRC among Hisp and NA. The unique ethnic diversity of New Mexico population,consisting of 45% non-Hisp Whites (NHW), 42% Hisp, and 10% NA, offers an ideal settingto assess ethnic differences in compliance rates to colonoscopy. The major aim of thisstudy was to determine the factors that were associated with non-attendance for scheduledcolonoscopy. Methods: We performed a retrospective analysis of 1147 consecutive scheduledcolonoscopies at a large open access tertiary center. Demographic data and reasons fornon-attendance were collected by chart review and telephone interviews. The strength ofassociations was assessed using a step-wise logistic regression analysis. Results: Among 1147patients scheduled for colonoscopy, 38% were NHW, 42% were Hisp, and 7% were NA.The overall nonattendance rate was 28.5%. The non-attendance rate for NHW was 21%.The attendance rate for Hisp was only about ½ of NHW [OR: 0.517 (CI= 0.380-0.703)]and NA was about ¼ of NHW [OR: 0.272 (CI = 0.165-0.448), indicating a 2-4 times highernon-compliance rate among Hisp and NA. Other factors that were significantly associatedwith higher non-attendance included marital status, insurance status, and age. Single patientswere more likely to miss their appointment than married patients (p= 0.0012). Patientswith public funded insurance had higher non-attendance rate than the privately insured(p<0.0001). Younger patients (< 50) had higher non-attendance rate than older patients (≥50) (p = 0.038). Of clinical importance was that the nonattendance rate for patients havingalarm features (guiaiac (+) stools or change in bowel movements) appeared to be similar tothose referred for elective screening purposes. Conclusion: Our results indicate for the firsttime that the non-attendance rate for scheduled colonoscopy is much higher (2-4 fold)among Hisp and NA than NHW. The higher non-attendance rate among Hisp and NA couldexplain the continued rise in CRC among these ethnic groups. Thus, future strategies thatimprove the compliance rate for colonoscopy in these ethnic groups could be crucial inreducing the incidence of CRC in Hisp and NA.

214

Expression of hPepT1 Aggravates Intestinal InflammationGuillaume Dalmasso, Hang Thi Thu Nguyen, Yutao Yan, Mauricio Rojas, Shanthi V.Sitaraman, Didier Merlin

Background & aims: The human di-tripeptide transporter hPepT1 plays a key role inmediating immune response by transporting bacterial peptides. hPepT1 is not expressed inthe colon but is induced in chronic inflamed colon, such as inflammatory bowel disease(IBD). Here we aimed at investigating the role of hPepT1 in IBD. Methods: To obtain strongand ubiquitous transgene expression in mice, we constructed a β-actin promoter-hPepT1expression vector. hPepT1 expression was assessed by immunohistochemistry, RT-PCR andWestern blot in several tissues. Transport activity of PepT1 in mouse colon was assessedby measuring PepT1-mediated lysine-proline-valine (KPV) uptake in colonic membranevesicles. Colitis in wild type (WT) and hPepT1 transgenic mice (hPepT1+/+) was inducedby 3% DSS or TNBS. Inflammation was assessed by MPO activity, an indicator of neutrophilsinfiltration, and by quantification of pro-inflammatory cytokines in mouse colon using real-time RT-PCR. For bone marrow transplants, mice were irradiated and received bone marrow(5 x 106 cells in 50μl were transplanted retroorbitally).Results: Themacroscopic examinationof body cavities, organs and tissues of hPepT1+/+ mice did not show any abnormal phenotype.Other tissues, such as skin, heart, lungs, thymus, exocrine pancreas, kidney, spinal cord,or ganglia of peripheral nervous system were unremarkable at the microscopic examination.Western blot analysis showed a strong ubiquitous hPepT1 expression in every tissue ofhPepT1+/+ mice. Colonic membrane vesicles from these mice exhibited a strong hPepT1expression and higher KPV uptake compared to WT mice, indicating that colonic hPepT1is functional. DSS and TNBS treatments induced more weight loss and neutrophil infiltrationinto colonic mucosa in hPepT1+/+ mice compared to WT mice. Furthermore, hPepT1+/+

mice exhibited higher mortality thanWTmice during the recovery phase after DSS treatment.Remarkably, DSS and TNBS induced drastically increased expression levels of pro-inflammat-ory cytokines (IL-1β, IL-6, IL-12, IFN-γ and TNF-α) in hPepT1+/+ mouse colon comparedto WT. Interestingly, DSS-induced IL-1β and IL-6 expressions in hPepT1+/+ myeloid cell-received WT mice were significantly reduced compared to WT myeloid cell-received hPepT1mice. These data suggest that hPepT1 expression in epithelial cells plays a key role inintestinal inflammation. Conclusions: Here we developed an In Vivo model to study thepathophysiological relevance of hPepT1 over-expression in IBD. Our data using this mousemodel demonstrate that expression of colonic hPepT1 observed during IBD may increasethe severity of the colitis.

215

Protective Role of EGFR in IL-10-Mediated ColitisPhilip E. Dubé, Kay Washington, D. Brent Polk

Epidermal growth factor receptor (EGFR) enhances intestinal epithelial homeostasis, restitu-tion and repair. Loss of EGFR ligands or inactivating EGFR mutations sensitize mice toacute colitis. We tested whether EGFR-inactivating mutations (EGFRwa2/wa2 or EGFRwa5)accelerate disease progression in the interleukin-10 knockout (IL-10-/-) chronic colitis model.METHODS: IL-10-/- mice with EGFRwa2/wa2 or EGFRwa5 mutations (collectively IL-10-/-

EGFRwa) were compared to IL-10-/- mice (all C57Bl/6 from the same colony). Controls werewildtype, EGFRwa2/wa2 and EGFRwa5 mice. Colonoscopy was performed between 6-28wk of