bluuebunny/crossref_metadata_2025 huggingface dataset:
A74 HELMINTH ANTIGENS OR REGULATORY MACROPHAGES REDUCE THE SEVERITY OF COLORECTAL CANCER
Authors: Callejas Pina B E , Wang A , Mendoza M , Terrazas L , McKay D M
Published: February 2020

Background

Infection with helminth parasites is a potent stimulus of immunity, and murine model systems reveal that a bystander benefit of this response to helminths is suppression of colitis. Unraveling the mechanism of this inhibition of colitis, the regulatory macrophage has emerged as a cell of interest in ‘helminth therapy’. Given the relationship between inflammation and cancer – patients with inflammatory bowel disease (IBD) have a higher risk of colorectal cancer (CRC).

Aims

To test the hypothesis that intraperitoneal administration of excretory/secretory products from the tapeworm Taenia crassiceps (TcES) or IL-4-treated macrophages (M(IL-4)) (characteristic of the immune response to helminths) would affect the outcome of CRC.

Methods

CRC was induced in female BALB/c and male C57Bl/6 mice using azoxymethane (AOM) (10 mg, ip) and three cycles of Dextran sulfate sodium (DSS: 7 days, 1–2% wt./vol.) separated by 2 weeks of normal tap water. Following initiation of CRC, mice received TcES (200 μg, ip.) - or M(IL-4) (106, ip). On necropsy, CRC incidence, number, and size of the tumour were recorded and tumors assessed histologically.

Results

Mice receiving TcES or M(IL-4)s were substantially protected from AOM-DSS induced CRC, as shown by statistically significant reductions in tumor number and size, although the number of mice developing tumors was unchanged (n=4–8 mice). The suppression of CRC in TcES-treated mice correlated with reduced mobilization of STAT3 and NF-κB signaling cascades in the as determined by immunostaining and immunoblot of whole tissue extracts.

Conclusions

With the speculation that helminth-derived molecules or transfer of in vitro educated macrophages could be used to treat IBD comes the specter of the putative oncogenic effects of regulatory macrophages. Contrary to this, the data herein show that the TcES reduced CRC; and, that murine macrophages (M(IL4)) also actually limit the severity of inflammation-driven CRC by directly targeting the cancer cells or reducing the inflammatory stimulus. These findings add emphasis to the consideration of autologous regulatory macrophage transfer to treat IBD and CRC

Funding Agencies

CCCCONACYT (Mexico)
A78 COMPARISON OF THE NICE, SANO, AND WASP CLASSIFICATIONS FOR OPTICAL DIAGNOSIS OF SMALL COLORECTAL POLYPS
Authors: Djinbachian R , Pohl H , Marchand E , Marques P , Bouin M , Deslandres E , Weber A , Bouchard S , Leduc R , Von Renteln D
Published: February 2020

Background

Optical diagnosis can be used as an alternative to pathology for the evaluation of colorectal polyps. There exist multiple classification systems that can be used to assist in performing optical diagnosis.

Aims

The aim of this study was to compare three different optical diagnosis classifications (NICE, SANO and WASP) when using Optivista and iScan image enhanced endoscopy (IEE).

Methods

The study included subjects between 45–80 years undergoing an elective screening, surveillance, or diagnostic colonoscopy with optical diagnosis using Optivista or iScan IEE. Three validated IEE scales (NICE, SANO and WASP classifications) were used for all optical diagnoses. Primary outcome was the agreement with pathology for surveillance intervals determined when using NICE, SANO and WASP for polyps 1-10mm. Secondary outcomes for polyps 1-10mm included accuracy of polyp diagnosis and negative predictive value (NPV) for rectosigmoid adenomas.

Results

A total of 399 patients were prospectively enrolled in the trial. The polyp detection and adenoma detection rates were 58.6% and 38.8% respectively. The proportion of correct surveillance interval assignment when at least one optical diagnosis was made was 92.9% when using NICE, 92.3% when using SANO, 89.5% when using WASP (p=0.656). Correct diagnosis was made for 74.2% of polyps when using NICE, 74.2% when using SANO, 65.6% when using WASP (p=0.012). The NPV for rectosigmoid adenomas was 91.2% when using NICE, 90.5% when using SANO, 87.5% when using WASP.

Conclusions

For optical diagnosis using Optivista and iScan IEE, all studied classifications performed equally for surveillance interval assignment. WASP had lower proportion of correct diagnoses on a polyp level and lower NPV for rectosigmoid adenomas.

Funding Agencies

None
A90 A UTILITY-BASED BAYESIAN OPTIMAL INTERVAL (U-BOIN) PHASE I/II DESIGN TO IDENTIFY THE OPTIMAL BIOLOGICAL DOSE FOR TARGETED AND IMMUNE THERAPIES
Authors: Zhou Y , Lee J , Yuan Y
Published: February 2020

Background

In the era of targeted therapy and immunotherapy, the objective of dose finding is often to identify the optimal biological dose (OBD), rather than the maximum tolerated dose (MTD).

Aims

To develop a utility-based Bayesian optimal interval (U-BOIN) phase I/II design to find the OBD.

Methods

We jointly model toxicity and efficacy using a multinomial-Dirichlet model, and employ a utility function to measure dose risk-benefit trade-off. The U-BOIN design consists of two seamlessly connected stages. In stage I, the Bayesian optimal interval (BOIN) design is used to quickly explore the dose space and collect preliminary toxicity and efficacy data. In stage II, in light of accumulating efficacy and toxicity from both stages I and II, we continuously update the posterior estimate of the utility for each dose after each cohort, and use this information to direct the dose assignment and selection. Compared to existing phase I/II designs, one prominent advantage of the U-BOIN design is its simplicity for implementation. Once the trial is designed, it can be easily applied using predetermined decision tables, without complex model fitting and estimation.

Results

Our simulation study shows that, despite its simplicity, the U-BOIN design is robust and has high accuracy to identify the OBD.

Conclusions

The U-BOIN design provide a practical, easy-to-implement method to identify the OBD for phase I-II clinical trials. It has great potential to accelate the drug development for GI diseases.

Funding Agencies

NIH
A93 HEPATOCELLULAR CARCINOMA SCREENING IN PATIENTS WITH CIRRHOSIS FOLLOWED BY A GASTROENTEROLOGIST- A RETROSPECTIVE STUDY OF HEALTHCARE QUALITY
Authors: Bourassa L , Décarie V , Beaudoin A
Published: February 2020

Background

The American Association for the Study of Liver Diseases (AASLD) guidelines recommend screening for hepatocellular carcinoma (HCC) in adults with cirrhosis every six months by abdominal ultrasound. This recommendation stands for patients with Child-Pugh A / B cirrhosis or Child-Pugh C who are on the transplant waiting list. The rationale behind this guideline is that surveillance for HCC has been shown to improve overall survival. However, in previous studies, rate of adherence to screening was suboptimal.

Aims

The goal of this study was to define the screening rate in our medical center while collecting demographic and descriptive data (Table 1).

Methods

We performed a monocentric retrospective study of healthcare quality. Adult patients who had a diagnosis of HCC between July 2010 and February 2018 and who were previously followed in gastroenterology for cirrhosis were included. The delay between the last abdominal imaging available and the first imaging that raised suspicion for or made the HCC diagnosis possible was calculated for each patient. Screening was considered appropriate if it was less than 8 months.

Results

102 of the 170 patients had to be excluded from the study because their cirrhosis wasn’t clearly documented before the HCC diagnosis (Figure 1). Amongst included patients, 52% (95% confidence interval 0,39-1,00) had received an appropriate screening for HCC.The average size of HCC at diagnosis was 37 mm and 53% had multicentric distribution. 56% of patients received treatment, with chemoembolization being the most frequently used in our population. 49% and 80% of patients had passed away at 1 and 3 years post-diagnosis, respectively. 52% of patients had normal alpha-feto-protein (AFP) initially.

Conclusions

Although limited in statistical power by the size of its sample, our study still sheds an interesting light on the reality of HCC screening in a Canadian hospital. The rate of appropriate screening, although suboptimal, is comparable to those reported in the literature elsewhere in the world. The dark prognosis associated with this disease is also illustrated. The proportion of patients who were excluded from the study due to occult cirrhosis highlights the importance of establishing this diagnosis so that screening recommendations can be put into practice. Further studies of larger scale would be needed to assess the causes of screening issues.

Funding Agencies

None
A102 MONOSODIUM GLUTAMATE INCREASES VISCERAL SENSITIVITY IN A MURINE MODEL OF IRRITABLE BOWEL SYNDROME
Authors: Brant B J , Yu Y , Lomax A E , Vanner S , Tuck C J
Published: February 2020

Background

Over 70% of patients suffering from symptoms of the irritable bowel syndrome (IBS) report that food is the most common trigger. Patients have identified that monosodium glutamate (MSG) is one food component that they suspect can trigger symptoms, but this remains unproven. As a first step towards establishing a potential role, we sought to examine whether there was a plausible mechanism of how MSG ingestion could underlie exaggerated pain signaling in IBS.

Aims

To examine the effects of MSG on visceral sensitivity in a murine model of IBS.

Methods

Balb/c mice were subjected to 6-days of water-avoidance stress (WAS) to create a pre-clinical model for IBS. To assess changes in visceral afferent nerve sensitivity in control and WAS mice, responses to ramp distension (0–60 mmHg), in the absence and presence 10 μM MSG perfused into the intestinal lumen (concentration based on diet analysis of MSG human ingestion), were recorded from afferent nerves innervating the jejunum ex vivo. To quantify these responses, the baseline firing frequency (spikes/second) was subtracted from the maximum response at each distending pressure. The relative distension response was calculated as a percentage of the control distension response (absence of MSG) (Figure 1). Jejunal preparations from the same WAS-treated mice were also used to measure ex vivo changes in mucosal permeability to MSG using Ussing chambers. We also ran the same distension protocol; however, we applied 10 μM MSG directly to the organ bath outside intestine obtained from control mice. This direct application would allow the MSG to have direct access to the nerve terminals without having to traverse the mucosa.

Results

The intraluminal administration of 10 μM MSG significantly increased afferent nerve sensitivity in WAS-treated jejunum but not controls. This response was significantly greater (23%) at pressures between 40 and 60 mmHg (p<0.01) (Figure 1). WAS-treated mouse jejunum was also significantly more permeable to MSG (p<0.05). Furthermore, the application of 10 μM MSG directly to the bath containing healthy jejunum significantly increased by 25% the sensitivity of afferent nerves specifically at 60 mmHg (p<0.01).

Conclusions

Our findings demonstrate that MSG increases visceral sensitivity to distension in our pre-clinical model of IBS. The increased permeability to MSG in WAS tissue and increased distension response in healthy control tissue when MSG is applied directly to the bath rather than intraluminally, suggests that MSG signals to the immune compartment or directly to the afferent nerve terminals. These findings support the rationale for future in vivo studies with this model to further clarify the mechanism.

Funding Agencies

CCC, CIHR
A115 MODELING CYSTIC FIBROSIS (CF) INTESTINAL DISEASE USING PATIENT DERIVED TISSUES
Authors: Xia S , Laselva O , Bear C E , Jones N
Published: February 2020

Background

Cystic Fibrosis is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes for a chloride/bicarbonate anion channel expressed on the apical membrane of most epithelial tissues, such as the lungs, liver, pancreas, small and large intestines, and reproductive tissues. CFTR is responsible for the transport of chloride and bicarbonate ions to maintain tissue surface hydration and pH balance of epithelial tissues. Historically, recurrent lung infections have been the most common cause of mortality in CF patients. With advances in clinical care and therapeutics, the current mean survival age of Canadian patients has increased to 52.3 years. However, this increase in survival has also been associated with an elevated risk of developing gastrointestinal cancers in CF adults. Compared to the general public, CF patients are 10 times more likely to develop cancer. This risk is increased to 25-20 times in patients that have undergone organ transplantations. Although the exact molecular mechanism regarding increased cancer risk in CF remains unclear, chronic intestinal inflammation has been known to contribute to elevated cancer development.

Aims

CF patients display an increased baseline inflammatory status that is exacerbated with microbiome exposure leading to possible increased risk for inflammation-mediated cancer development.

Methods

To reduce inter-patient heterogeneity, we have differentiated human intestinal organoids using induced pluripotent stem cells from homozygous F508del CF patients and gene edited isogenic non-CF (Wt-CFTR) controls. We conducted gene expression studies using RT-qPCR to determine baseline differences in gene expression prior to environmental exposures and following exposure to LPS and flagellin.

Results

We determined the expression levels of stem cell, intestinal epithelial cell, innate immunity genes and differentiation markers and found expression of such genes were not significantly different between 3D CF and gene-edited non-CF organoids. We are currently conducting RNA sequencing to survey expression pattern of all genes to definitively determine possible fundamental changes in the CF intestinal epithelium and determining the effect of LPS and flagellin treatment to determine if there is an altered response to inflammatory stimuli.

Conclusions

iPSC derived HIOs is a novel, patient based, and renewable model that can be used to dissect the primary intestinal pathologies in CF. Transcriptomic data of CF HIOs at steady state will provide insights to possible developmental defects. Complex interactions between the host intestinal epithelia and the commensal microbiome can also be investigated using this model.

Funding Agencies

CAG
A128 JACKHAMMER ESOPHAGUS – A META-ANALYSIS OF PATIENT DEMOGRAPHICS, DISEASE PRESENTATION, MANOMETRY DATA AND TREATMENT OUTCOMES
Authors: Wahba G , Bouin M
Published: February 2020

Background

Jackhammer esophagus (JE) is a newly described esophageal motility disorder characterized by the presence of distal esophageal hypercontractility. However, there is limited data on JE and this entity remains misunderstood.

Aims

To systematically review the published clinical data on JE and present pooled data on patient demographics, disease presentation, manometry parameters and treatment outcomes from the available literature.

Methods

We performed a systematic review of clinical series on JE (based on the latest Chicago Classification criteria (v3.0)) through MEDLINE, EMBASE and Web of Science. Patient data from included studies were then extracted and random-effects meta-analyses were performed to calculate and compare pooled data.

Results

Thirty-seven studies met inclusion criteria reporting on at least one pooled variable. The pooled prevalence of JE was 1.97% [95% CI: 1.39%-2.78%] amongst patients referred for high resolution manometry (HRM) based on eleven studies reporting this data (Figure 1). The mean age at diagnosis was 60.8 years [95% CI: 57.1–64.4] and 65% [95% CI: 58%-72%] of patients were female. JE was significantly more prevalent in post-lung transplant patients and morbidly obese patients undergoing HRM (23.99% [95% CI: 9.00%-38.97%] and 5.18% [95% CI: 1.76%-14.3%] respectively). Dysphagia was the most common presentation of JE (64% [95% CI: 52%-77%]) followed by gastroesophageal reflux disease (GERD) (46% [95% CI: 26%-67%]), regurgitation (39% [95% CI: 10%-67%] and heartburn (34% [95% CI: 22%-45%]). The pooled mean distal contractile integer (DCI) of all ten standard HRM swallows was 9,535 mmHg●s●cm [95% CI: 6,978–12,093] and the pooled mean integrated relaxation pressure (IRP) was 13.9 mmHg [95% CI: 8.2–19.7]. Endoscopic treatment as a whole was more successful than medical treatment in achieving clinical symptom improvement (79% [95% CI: 74%-85%] vs. 63% [95% CI: 47%-79%]; p=0.012). The pooled clinical success rate of peroral endoscopic myotomy (POEM) specifically was 82% [95% CI: 75%-90%].

Conclusions

JE is a new motility disorder most commonly presenting with dysphagia. High clinical suspicion is important because the diagnosis can only be made through HRM and treatment outcomes are generally satisfactory.

Funding Agencies

None
A140 UNDERSTANDING PATIENTS’ PERCEPTIONS OF FECAL MICROBIOTA TRANSPLANT
Authors: Chauhan U , Popov J , Kalantar M , Wolfe M , Marshall J , Halder S L , Moayyedi P , Kaasalainen S
Published: February 2020

Background

Fecal microbiota transplantation (FMT) is under active investigation as a popular treatment option for a variety of diseases, including ulcerative colitis (UC). Despite increasing evidence for its therapeutic role, the current literature is limited in its scope to assess firsthand patient experiences.

Aims

To exlore perceptions, attitudes, and experiences of patients who chose to pursue FMT and patients who declined FMT in favor of conventional medications.

Methods

Using qualitative descriptive design, eligible patients were invited to participate in face-to-face semi-structured interviews before and after FMT treatment. Interviews were audiotaped, transcribed, and analyzed using thematic analysis.

Results

Main baseline themes across the FMT (n=9) and non-FMT (n=8) groups included: (i) knowledge of FMT, (ii) attitudes around FMT, and (iii) factors contributing to the decision to pursue FMT. Post-FMT themes included: (i) experiences with FMT, and (ii) perceived response to treatment. We found a poor general understanding of FMT across both cohorts, suggesting a need for improving patient education. Non-FMT patients were less likely to have heard or researched FMT in the past due to feelings of “it just sounds weird”. Similar concerns were found across both groups, including fear of transmissible infections, cost of an experimental therapy, and aversion to stool. Expectations varied between the two groups, with feelings of hope and a sense of “last resort” driving patients to pursue FMT. In contrast, the non-FMT cohort felt a need to further research FMT, explore other treatment options before committing to FMT, and were more likely to describe their disease activity as “not at the severe end”. This demonstrates that FMT may be perceived as a “last ditch effort”. Despite initial aversion, the non-FMT group demonstrated interest in learning more about FMT and felt more open to the possibility of pursuing FMT in the future. The FMT group was more likely to harbor a positive view of natural medicine and classify FMT as natural, while the non-FMT cohort expressed “I’m not really into the weird stuff”. Post-FMT, some patients expressed delight in the perceived changes in their symptoms, including improved quality of life, decreased urgency, and less concerns with accidents.

Conclusions

Our results suggest that important motivating factors for pursuing FMT are a perception of naturality and a sense of last resort. With improved education, FMT may pose an acceptable and tolerable treatment option for patients with UC.

Funding Agencies

Canadian IBD (CANIBD) Nursing
A147 ENDOSCOPIST FEEDBACK IS ASSOCIATED WITH IMPROVEMENTS IN COLONOSCOPY QUALITY INDICATORS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Bishay K , Calo N , Scaffidi M A , Walsh C M , Anderson J , Rostom A , Dube C , Keswani R N , Heitman S , Hilsden R J , Shorr R , Grover S C , González Moreno E , Forbes N
Published: February 2020

Background

Colonoscopy quality indicators such as adenoma detection rate (ADR) are surrogates for the effectiveness of screening-related colonoscopy. Endosocpist feedback may be associated with improvements in ADR and other quality indicators.

Aims

To conduct a systematic review and meta-analysis to determine whether an association exists between endoscopist feedback and improvements in colonoscopy quality indicators.

Methods

An electronic and manual search was conducted through May 2019 for studies reporting on endoscopist feedback and associations with ADR or other colonoscopy quality indicators. Studies primarily assessing the effect of audit and feedback on trainees and studies that included interventions other then feedback were excluded from the analysis. Pooled rate ratios (RR) and weighted mean differences (WMD) were calculated using DerSimonian and Laird random effects models. Subgroup, sensitivity and meta-regression analyses were performed to assess for potential methodological or clinical factors associated with outcomes.

Results

Of 1,326 initial studies, 12 studies were included in the meta-analysis for ADR, representing 33,184 colonoscopies. Endoscopist feedback was associated with an improvement in ADR (RR 1.21, 95% confidence interval, CI, 1.09 to 1.34). Low performers derived a greater benefit from feedback (RR 1.62, 95% CI 1.18 to 2.23) compared to moderate performers (RR 1.19, 95% CI 1.11 to 1.29), while high performers did not derive a significant benefit (RR 1.06, 95% CI 0.99 to 1.13). Feedback was not associated with increases in withdrawal time (WMD +0.43 minutes, 95% CI -0.50 to +1.36 minutes) or improvements in cecal intubation rate (RR 1.00, 95% CI 0.99 to 1.01).

Conclusions

Endoscopist feedback is associated with modest improvements in ADR. Routine audit and feedback may be a feasible strategy to optimize outcomes in screening colonoscopy.

Funding Agencies

None
A149 COMPARING THE REAL-WORLD EFFECTIVENESS OF 4L VERSUS 2L SPLIT COLONOSCOPY PREPARATIONS: PRELIMINARY DATA OF A SINGLE CENTRE EXPERIENCE THROUGH THE BRITISH COLUMBIA COLONOSCOPY SCREENING PROGRAM
Authors: Lee J G , Telford J J , Galorport C , Yonge J , Macdonnell C A , Gillies A , Chow R , Enns R A
Published: February 2020

Background

The British Columbia Colon Screening Program (CSP) is a population-based program offering biennial fecal immunochemical test (FIT) to individuals age 50–74 years with follow-up colonoscopy for a positive FIT as well as individuals with a personal history of neoplastic polyps or a high risk family history of colorectal cancer. Over 20,000 colonoscopies are performed annually. In December 2018, program colonoscopists in Vancouver, Canada agreed to switch from a 2L polyethylene glycol (PEG) preparation to a 4L PEG preparation after studies suggested superiority of the higher volume preparation in achieving adequate bowel cleansing and improving adenoma detection rates (ADR). High quality bowel cleansing is critical to minimize repeat procedures and maximize neoplasia detection.

Aims

To compare the quality of bowel preparation and neoplasia detection rates using the 4L high volume split preparation (HVSP) versus the 2L low volume split preparation (LVSP) in patients undergoing colonoscopy in the BC CSP.

Methods

A retrospective review of consecutive patients undergoing colonoscopy through the CSP at St. Paul’s Hospital from Dec 2017-Apr 2018 and Dec 2018-Apr 2019 was conducted. Inclusion criteria included: age 50–74, patients undergoing colonoscopy for any reason through the BC CSP. Variables collected included: patient demographics, bowel preparation qualty and pathologic findings. ADR and sessile serrated polyp detection rate (SSDR) were analyzed.

Results

462 colonoscopies were included, 280 in the LVSP group and 182 in the HVSP group. 8/280 (2.9%) had poor bowel preparation in the LVSP group, while 10/182 (5.5%) had poor bowel preparation in the HVSP group. The ADR and SSDR were 53.6% in LVSP vs. 50.0% in HVSP and 8.2% in LVSP vs. 8.8% in HVSP, respectively.

Conclusions

In this preliminary evaluation, the high volume PEG-based split preparation did not reduce the proportion of inadequate bowel preparations. Further evaluation of a larger number of colonoscopies is planned.

Funding Agencies

None
A150 ACCESS TIMES TO GASTROENTEROLOGY FOR HIGH-RISK IBD REFERRALS IN THE GREATER CALGARY REGION
Authors: St-Pierre J , Oshiomogho I , Bindra G , Kaplan G G , Panaccione R , Seow C , Nasser Y , Beck P , Jijon H
Published: February 2020

Background

Delay in the diagnosis of inflammatory bowel disease (IBD) can lead to adverse outcomes. In 2006, the CAG Wait Time Consensus Group recommended that wait times for patients with symptoms highly suggestive of IBD should be seen within two weeks. In 2007, the greater Calgary region established a central access and triage system to improve access to care as well as the “High-Risk IBD clinic” (HR-IBD) to further expedite the access of patients with IBD alarm symptoms. These included diarrhea, rectal bleeding, weight loss, abnormalities in laboratory and stool investigations.

Aims

The current study aimed to evaluate whether patient access to the HR-IBD clinic in the Calgary region was within recommended wait times.

Methods

We conducted a cross-sectional study of charts from consented patients pulled from the EMR of five Gastroenterologists in the Calgary region that received HR-IBD referrals from Feb 2014 to Jan 2018. Of the 206 patients included, the majority were female (139 vs 65) and the mean age was 34.4 y, with no statistical difference in age between genders (p=0.81). Data analysis was done with Stata (StataCorp 2019).

Results

The mean time to initial consult was 74.8 days (median 64), whereas time to endoscopy was 85.5 days (median 77). There was no statistical difference in the mean wait times between genders. Of the patient charts reviewed, 27% of referrals had a confirmed diagnosis of IBD (CD 17%, UC 11%). Patients with a diagnosis of UC waited a mean of 60.1 days (median 60) until initial consultation and patients with a diagnosis of CD waited 77 days (median 63.5), although this was not statistically different (p=0.27). The mean time to endoscopy for patients with UC was 77 days (median 67), and 85.4 days for patients with CD (median 78.5), again not statistically different. These wait times are below the reported wait times for all GI complaints, of 92 days from referral to consultation and 155 days from referral to procedure, as reported in the SAGE survey (2012). Although there were no differences in time to consult and endoscopy between groups, there were notable differences in alarm symptoms reported in the referral. For example, rectal bleeding was reported in 81.8% of referrals that culminated in a diagnosis of UC, as compared to 50% in CD and 47.6% of non-IBD patients. Further analysis in which alarm symptoms correlate with a final diagnosis of IBD may guide triaging of referrals to decrease the time to diagnosis.

Conclusions

Timely access for consultation and endoscopy for patients presenting with high-risk features for IBD by Gastroenterology in the Calgary region remains above the CAG recommended wait times. Further correlation of high-risk features with a final diagnosis of IBD will help risk-stratify referrals in order to decrease time to IBD diagnosis.

Funding Agencies

CIHRAlberta Innovates Health Solutions
A157 THE EFFECTIVENESS OF A STANDARDIZED BIOLOGIC CARE PATHWAY IN THE MANAGEMENT AND TREATMENT OF INFLAMMATORY BOWEL DISEASE
Authors: Willett N , Heisler C , Nazer N , Currie B , Phalen-Kelly K , Stewart M , Jones J
Published: February 2020

Background

Inflammatory Bowel Disease (IBD) is a class of chronic immune-mediated diseases. Biologics have revolutionized the treatment of IBD. Existing literature suggests significant variation exists in the use of biologic treatment among physicians, from provider-specific prescribing to completion of the pre-biologic workup. These differences may influence the effectiveness of achieving and maintaining long-term remission. Clinical care pathways may serve to standardize the use of biologics in the treatment of IBD leading to improvements in patient outcomes and consistency of care provided from different specialists.

Aims

To determine if the use of biologics to treat IBD managed within a standardized biologic care pathway (BCP) is safer and more effective compared to the current standard of care.

Methods

This was a retrospective, real-world cohort study of a prospectively implemented evidence-based BCP at the Nova Scotia Collaborative IBD (NSCIBD) program between 2015 and 2019. Patient inclusion criteria consisted of any adult with a diagnosis of IBD (including Crohn’s Disease, ulcerative colitis, IBD-Unclassified) aged 18 years or older who was managed within the NSCIBD program. Preliminary descriptive analyses of the data are presented. Data collection is ongoing and multivariate analyses will be presented in full at CDDW.

Results

In total 249 patients were included in the cohort study (111 BCP patients, 138 non-BCP patients). The mean age was 49 years (range of 17–86 years). Sixty-nine percent (171/249) of patients were diagnosed with CD, 28% (70/249) with UC, and 3% (8/249) with IBD-U. The mean duration of disease was 13 years (range of 0–36 years). Use of combination therapy was similar between the cohorts with 64% of BCP patients (n=102) and 63% of non-BCP patients (n=123) on combination therapy. Thirty-eight percent of the BCP cohort required dosing interval changes vs. 29% in the non-BCP cohort (0.24 fold higher in BCP cohort). Seventy-one percent of the BCP patients were exposed to TDM vs. 41% of the non-BCP cohort (0.40-fold more TDM in pathway cohort). Although 34% of BCP patients and 38% of non-BCP cohort patients reached clinical remission (n=103 and 125, respectively), 38% of BCP patients and 21% of non-BCP patients achieved endoscopic remission (0.5-fold lower in the non-BCP cohort), (n=29 and 53, respectively).

Conclusions

Preliminary analyses suggest patients managed within a BCP have their biologic management guided more often by the results of TDM and objective biomarkers than those not managed within a BCP. Although clinical remission was observed to be similar between the cohorts, attainment of endoscopic remission was more likely amongst patients managed within the BCP. Additional multivariate analyses will be presented at CDDW with a larger cohort size.

Funding Agencies

None
A166 ANALYSIS OF SYMPTOMS, DIAGNOSTIC PATTERNS, AND CANADIAN PROVIDER PERSPECTIVE OF ACUTE HEPATIC PORPHYRIA
Authors: Roblin S , Meninger S , Murray S , Karki C , Krautwurst K , Mustafina R , Ko J
Published: February 2020

Background

Acute hepatic porphyria (AHP) is a family of rare genetic diseases, the most common being acute intermittent porphyria (AIP). AHP results from enzyme deficiencies involved in haem synthesis, leading to accumulation of neurotoxic haem intermediates, aminolaevulinic acid (ALA) and porphobilinogen (PBG), causing potentially life-threatening attacks and chronic symptoms. Patients afflicted by AHP often remain without a proper diagnosis for up to 15 years due to lack of awareness and testing. First-line diagnostic biochemical tests include measuring spot urinary ALA and PBG as both are elevated in the majority of AHP patients.

Aims

The study aimed to describe physicians experience diagnosing AHP and characterize patients globally, including Canada.

Methods

Physicians (n=175) who actively managed AHP patients (with and without recurrent attacks) in the preceding year were recruited from 9/2017–10/2017 to complete an online survey collecting information on demographics, familiarity with AHP and diagnostic tests, perspective on symptoms important to diagnosis, referral patterns, and treatment preferences. Physicians also completed a chart review of 546 patients and reported anonymized data on demographics, medical history, attacks, and symptoms. Data was analysed using descriptive statistics.

Results

Canadian physicians (n=15) practiced a mean of 19.7 years, 67% worked in community settings, and 53% were gastroenterologists. Symptoms informing AHP diagnosis included fatigue (93%), sensory loss (87%), mental confusion (87%), Abdominal pain (80%), red/dark urine (80%), vomiting (73%). AHP diagnostic tests considered informative for diagnosis included urinary ALA (87%) and PBG (80%); however, several non-specific tests were also commonly considered informative of AHP. Chronic symptoms reported included fatigue (75%), nausea/vomiting (70%), weakness (66%), pain (58%), anxiety (54%), diarrhea (41%), constipation (40%). Canadian physicians reported a mean of 58% AHP patients they manage being initially misdiagnosed. Global patients (n=546) were aged 40 years (mean), female (52%), with AIP (83%). Canadian patients (n=38) were aged 41 years (mean), female (61%), with AIP (78%). Patients had mean of 3.4 attacks and 1.6 hospitalizations in the past year.

Conclusions

This study highlights the challenges diagnosing AHP due to non-specificity of symptoms and limited understanding of diagnostic procedures. Due to the frequent presentation of gastrointestinal symptoms, AHP should be included in gastroenterologists’ differential diagnosis of patients presenting with non-specific abdominal pain. Among patients diagnosed with AHP, both acute attacks and chronic symptoms were reported, implicating both in the disease.

Funding Agencies

Alnylam Pharmaceuticals
A173 RECOGNIZING RARE PRESENTATIONS OF POLYPOSIS SYNDROMES AND THEIR ASSOCIATED MALIGNANCIES IN PEDIATRIC PATIENTS
Authors: Reitzel N E , Sherlock M , Zachos M , Arredondo J , Ratcliffe E
Published: February 2020

Background

There is a range of polyposis syndromes and presentations in pediatrics. There are also associated extra-colonic malignancies of which to be cognizant when orchestrating the initial work-up of the various polyposis syndromes.

Aims

To use case review to highlight the importance of recognizing the breadth of presentations of polyposis syndromes in pediatrics.

Methods

Two recent pediatric presentations of polyposis with extra-intestinal manifestations were identified, chart review completed, and compared with newly published ESPGHAN guidelines.

Results

Two patients with intestinal polyposis are presented, in which extra-colonic malignancies and genetic mutations were identified.

The first patient presented at age 16 with a history of fatigue and abdominal pain, and was found to have pancytopenia and splenomegaly. Initial work up included a bone marrow biopsy that was normal. The patient then underwent upper and lower endoscopic evaluation for increasing abdominal pain and persistent anemia and was found to have polymorphic polyps in the duodenum, sigmoid and rectum. On pathology, polyps were mostly inflammatory, but one was found to be hamartomatous. Additional screening revealed a thyroid nodule, found to be follicular carcinoma, requiring hemithyroidectomy. The patient was confirmed to have a PTEN mutation and was diagnosed with Cowden syndrome; following this diagnosis proceeded with a prophylactic bilateral mastectomy.

The second patient was referred at age 15 with a strong family history of APC-associated FAP. At the time of consultation she was asymptomatic and she remained so throughout her work-up. Screening endoscopy revealed 70–90 recto-sigmoid adenomatous polyps as well as scattered gastric and duodenal polyps. Her initial work-up also uncovered an early papillary thyroid carcinoma. Her treatment included a total thyroidectomy and total proctocolectomy with J-pouch and ileoanal anastomosis. Follow-up endoscopy continues for surveillance of numerous gastric adenomas which to this point have not progressed to high-grade dysplasia or malignancy.

Conclusions

These 2 cases highlight the importance of recognizing that neoplastic conditions typically diagnosed in adulthood can also present in the pediatric age group. Ideally, further guidelines in pediatrics would be beneficial to ensure a consistent approach to investigating polyposis and associated malignancies. Pertaining to our specific patients, each had identification of a thyroid malignancy before the recommended screening age of 18 as per the currently accepted guideline, and neither were symptomatic. More cases are needed to establish if this earlier recognition of disease is meaningful in postulating potential mortality associated with a later diagnosis.

Funding Agencies

None
A175 RECURRENT GASTROINTESTINAL BLEED – A LATE MANIFESTATION OF COLONIC TUBERCULOSIS TREATED CONSERVATIVELY
Authors: Tan J , Hejazifar N , Vantomme E , Tsoi K
Published: February 2020

Background

The incidence of active tuberculosis (TB) in Canada is 4.8 per 100000 persons. Globally, gastrointestinal (GI) TB is rare and accounts for 5% of all extra-pulmonary cases. Clinical manifestations of intestinal TB include weight loss (75%), abdominal pain (54%), and changes in bowel habits (50%). GI bleeding has been observed in 5–15% of confirmed cases of colorectal TB. The cecum is the most common site of involvement, with the most common gross finding on colonoscopy being ulcerations (88%), and the least common being polypoid lesions (10%). Intestinal TB is treated the same as pulmonary TB, with endoscopic healing observed in the majority of cases following 9 months of anti-TB therapy. Surgery is entertained in cases of non-resolving obstruction, perforation, or fistula formation.

Aims

Management of stable, recurrent, large volume GI bleeding in TB colitis is not well established. We report such a case that resolved solely by anti-TB regimen.

Methods

Case report

Results

A 56 year old man with chronic kidney disease presented with cachexia and 40 pound weight loss over 6 months after return from India. He underwent computerized tomography scan of his chest, abdomen and pelvis. Multiple, large, cavitary lesions in the right upper lung lobe were seen, and confirmed to be TB by bronchoalveolar lavage. Abdominal imaging identified moderate circumferential wall thickening at the cecum concerning for intestinal TB. These findings were also retrospectively noted on a review of an abdominal MRI 4 months prior.

His course was complicated by episodes of large, alternating bright red blood per rectum and melena stools starting 5 days after initiation of anti-TB therapy. Colonoscopy revealed polypoid lesions in the cecum as well as blood throughout the colon, with no active source of bleeding. Surgery was considered for ongoing bleeding, however, because biopsies were negative for malignancy and positive on acid-fast stain, he continued conservative management with blood transfusions and anti-TB therapy. GI bleeding decreased significantly within the first 2 weeks, and resolved by day 25. He completed 1 year of anti-TB therapy, with no signs of colitis detected radiographically at the 6-month mark.

Conclusions

To our knowledge, this is the first report of GI bleeding as a very late manifestation of colonic TB, resolved with anti-TB therapy alone. Time from initial evidence of intestinal TB on imaging to the first bleed was 159 days, and time from initial symptoms was 6 months. As polypoid lesions are the least common gross finding on colonoscopy, a high degree of suspicion should be held in the right clinical setting. Surgical management should be considered only after conventional anti-TB therapy has failed.

Funding Agencies

None
A182 LAST RESORT – RESOLVING REFRACTORY UPPER GI BLEEDS WITH ENDOSCOPIC APPLICATION OF FIBRIN GLUE
Authors: Enns C J , Dhalla S , Corcoran M
Published: February 2020

Background

Endoscopic assessment of gastric bleeding is essential for timely investigation and evaluation in attempting to resolve bleeds. Increasingly, endotherapy is used to stop bleeds to prevent the patient from progressing to surgery. The tools available for the endoscopist can be broadly broke into injection sclerotherapy, mechanical tamponade, thermal methods and Hemospray©. Each method has their own inherent advantages and disadvantages with indications for use.

Aims

Unfortunately, patients fail despite standard endotherapy and would then be subjected to surgical procedures. Fibrin glue injection has been selectively described in case reports to resolve recalcitrant bleeds. We have reviewed endotherapy cases by one surgeon where fibrin glue was used to resolve recalcitrant upper gastrointestinal bleeding in a variety of clinical presentations. The goal was to show that endotherapy application of fibrin glue can be used to resolve challenging GI bleeds.

Methods

A retrospective review was made from one surgeon records of endoscopic bleed resolution with fibrin glue from 2010 to 2018. Indications for the procedure were gastric bleeds in hospital, emergency department, or undergoing endoscopic procedures that resulted in a heavy bleed. Patients were categorized as high risk using the Rockall score and those with known ulcers ertr graded as Forest Ia. The patients were of a variety of ages, sex, and had differing co-morbid medical conditions. The fibrin product used was Tisseel which is a two-component fibrin sealant and was deployed using a standard endoscopic Injection sclerotherapy needle.

Results

In all but one of the patients, hemostasis had been reached by delivering fibrin glue by endoscopy. The patient that failed treatment had multiple co-morbidities and the bleeding source was a gastric bed of venous malformations. Patients were followed up with next day scoping to confirm bleed hemostasis. No adverse reactions were noted.

Conclusions

Studies have shown in the past that fibrin glue has worked in achieving hemostasis and had a lower rate of re-bleeding. There are several advantages to using the biological process of the clotting system. The fibrin mat will stay localized and not spread into the lesion. Fibrin injection also creates the natural meshwork of normal biological healing. This naturally compress the mat meshwork along the wound and promote hemostasis. Fibrin glue can also be re-applied in the case of a site re-bleed. Treating endoscopically can beneficial in that patients may not need to progress to the risks and recovery times of surgery. Utilizing the biological process of the body allows for natural repair and degradation of the clot. The procedure is well tolerated and had showed no side effects in this review. Our findings support the use of fibrin glue injection endotherapy as a last resort before surgical intervention.

Funding Agencies

None
A183 UPPER GASTROINTESTINAL CAUSTIC INJURIES: A SINGLE CENTRE CASE SERIES
Authors: Monachese M , Griller N , Yong E
Published: February 2020

Background

Caustic esophageal and gastric injury is a rare, but potentially lethal event. The 2017 American Association of Poison Control reported only 193,000 cases of caustic ingestion (1). Caustic agents are acidic or alkaline. The pH of the ingested substance dictates the type of injury and the area of the gastrointestinal track most at risk. The most common culprit agents are alkaline including, for example, bleaches, drain openers and dishwashing detergents. Due to the rarity and natural history of this disease there are very few high-quality studies for clinicians to refer to when managing these patients.

Aims

We present three cases of caustic ingestion and provide a review of current best practice standards.

Methods

Between August and September 2019, three patients were admitted to Sunnybrook Health Sciences Centre at the University of Toronto for caustic injury. All three patients were referred to the gastroenterology service and underwent an esophagogastroduodenoscopy (EGD) to assess the degree of esophageal and gastric injury. Patients were followed both in hospital and in the outpatient setting for ongoing surveillance and repeated endoscopic evaluation. Patient demographics, treatment, endoscopic findings and outcomes were collected.

Results

Three patients intentionally ingested caustic agents, were admitted to hospital and managed by the gastroenterology service. Patients were a mix of ages, genders and ethnicities. All ingestions were strong alkali agents including sodium hydroxide and sodium hypochlorite. All patients underwent an EGD within 24 hours of presentation and caustic injury was graded using the Zargar classification (2). All patients were started on intravenous proton pump inhibitor therapy. All patients were initially made nothing per mouth and ability to resume feeds was assessed based on symptoms. Patient 1, Zargar grade 1, was able to resume oral intake within 48 hours and progressed to a regular diet without complications. Patient 2, Zargar grade 2a, required 5 days of TPN and bowel rest after which a liquid diet was initiated and advanced without complications. The third patient, had a severe injury (Zargar grade 3b), requiring a prolonged hospital stay. He was on TPN for three weeks before transitioned to tube feeds.

Conclusions

Caustic mucosal injuries are an infrequent, but potentially lethal event requiring urgent assessment and management by a team including gastroenterologists, thoracic and abdominal surgeons, dieticians and intensivists. High-quality evidence to guide management of caustic injuries remains limited. In our case series, there was a wide spectrum of degree of mucosal injury. All 3 patients were managed in a consistent fashion based on current recommendations. Two of three cases had a rapid recovery with the ability to resume oral intake and return home. The third patient remains in hospital, requiring a high level of supportive care.

Funding Agencies

None