bluuebunny/crossref_metadata_2025_split huggingface dataset:
A168 IS ROUTINE SCREENING FOR HEREDITARY COLORECTAL CANCER FEASIBLE IN AN OUTPATIENT GASTROENTEROLOGY PRACTICE?
Authors: Smith B C , Yonge J , Macdonnell C A , Poon J , Galorport C , Gillies A , Chow R , Enns R A , Telford J J 
Published: February 2020

Abstract

Background
Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer (CRC), with a reported prevalence of 2–5% of all CRC cases. A study by Kastrinos et al. found that a simple 3 item survey identified 77% of individuals at high risk for hereditary CRC. Implementation of this questionnaire at a gastroenterology office may help identify patients at risk for LS and other hereditary CRC.

Aims
To assess whether implementation of a validated questionnaire to screen for hereditary CRC is feasible in an outpatient gastroenterology clinic.

Methods
Adult gastroenterology outpatients who consented to participate in the study completed the screening questionnaire. Those who had previously been assessed by the Hereditary Cancer Program were excluded. Each subject was asked the following three questions: (1) Do you have a first-degree relative with CRC or LS-related cancer diagnosed before age 50? (2) Have you had CRC or polyps diagnosed before age 50? (3) Do you have ≥3 relatives with CRC?. Answering yes to any question was considered a positive screen.

Results
A total of 288 patients were screened, with 12 (4.2%) screening positive for question 1, 28 (9.7%) screening positive for question 2, and 8 (2.8%) screening positive for question 3. In total, 14.2% of individuals surveyed screened positive.

Conclusions
Utilization of a simple 3-question survey as part of regular patient intake in a gastroenterology office resulted in 14.2% of individuals screening high-risk for hereditary CRC. This is similar to the 15% screen positive rate in the original study of individuals with CRC. Further research is needed to determine whether a physician’s knowledge of the questionnaire results will change management and whether a positive screen leads to a confirmed diagnosis of LS and other hereditary colorectal cancers.

Funding Agencies
None
A169 DEVELOPMENT OF A DECISION TOOL TO IMPROVE UTILISATION OF RECOMMENDED SURVEILLANCE INTERVALS FOR INDIVIDUALS WITH COLORECTAL POLYPS: A FOCUS GROUP ANALYSIS
Authors: Lee E , Singh H , Simms A , Restall G , Shafer L , Walker J , Park J 
Published: February 2020

Abstract

Background
Several studies have demonstrated a high utilization of colonoscopy at shorter and longer time intervals than guideline recommendations. Innovative methods are required to increase adherence to recommended timing.

Aims
1) Explore current approaches used by endoscopist (EPs) and primary care providers (PCPs) to determine and communicate colonoscopy surveillance intervals (SI) between EPs, PCPs, and patients.
2) Obtain feedback for refining a decision tool to facilitate recommended SI.
3) Determine participant agreement of recommended SIs with current guidelines.

Methods
We conducted 4 focus groups (FGs); 3 FGs included EPs (n=12) and EPs in training (n=6); 1 FG included PCPs (n=4). FG questions explored use of guidelines, communication and follow-up practices with PCPs, EPs and patients, and challenges to follow-up.
Participants were also asked for feedback about a prototype polyp SI decision tool that was developed using an algorithm synthesizing current Canadian Association of Gastroenterology, US Multisociety Task Force, and expert panel guidelines on SI. FGs were audio-recorded and transcribed for qualitative content analysis. FGs were analysed separately, then compared for similarities and differences. Finally, participants individually made interval recommendations for 7 common endoscopy scenarios. Responses were analyzed for agreement with the guidelines used to develop the decision tool.

Results
EPs reported not routinely referring to guidelines and were confident in their memory of the intervals although some reported checking occasionally. Many indicated they may use the tool in a web based or mobile application for more complicated scenarios, although some would never use it. Concerns regarding the tool included being up to date with research evidence and having required data to input on hand. PCPs reported the tool may be useful as a communication aid to involve patients in decision making. A challenge noted in all FGs was role confusion regarding communicating, tracking, and scheduling patients’ future procedures on time.
Analysis of EPs (n=9) responses to the 7 scenarios showed that percent agreement with guidelines was low: 44% scored below 50% correct. Participants with the highest agreement scored 6/7; responses with the lowest agreement scored 0/7. The most common score was 3/7.

Conclusions
EPs appeared to be overconfident in their recommendations, but many were open to trying a website or mobile application decision tool to make evidence-based colonoscopy SI recommendations. Understanding, among PCPs and EPs, regarding responsibility for communicating results and scheduling follow-up surveillance for patients was inconsistent. Participant feedback informed development of a mobile application that is currently being pilot tested.

Funding Agencies
Research Manitoba
A174 RARE BUT DEADLY: AN APPROACH TO MANAGEMENT OF DUODENAL VARICEAL HEMORRHAGE
Authors: Dahiya M , Tomaszewski M , Ou G , Ramji A 
Published: February 2020

Abstract

Background
Common etiologies of upper gastrointestinal bleeding (UGIB) in cirrhotic patients with portal hypertension include gastroesophageal varices (GOV), portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE). Less commonly, patients with portal hypertension develop varices in ectopic sites, including the rectum, biliary tree and duodenum. Ectopic varices are rare, contributing to 1–5% of all variceal bleeding, of which 17% is from duodenal varices.

Aims
To describe the management of duodenal variceal hemorrhage.

Methods
A case report and literature review was performed.

Results
Case report:
We present a case of recurrent UGIB in a 59-year-old male with decompensated cirrhosis due to non-alcoholic steatohepatitis (CP-C; Meld 14). Initial endoscopy was negative for GOV, peptic ulcer, PHG, and GAVE, but an erosion over a mucosal bulge in the third segment of the duodenum was identified, raising possibility of vascular malformation versus ectopic varix. There was active bleeding after water provocation, so clips were deployed for hemostasis. CT imaging showed mesenteric venous collaterals abutting the duodenum, again raising possibility of duodenal varix, which was ultimately confirmed by endoscopic ultrasound (EUS). Patient had recurrent overt bleeding despite beta-blockage for prophylaxis, endoscopic clipping on four separate occasions, attempted angioembolization by interventional radiology, and cyanoacrylate glue. Transjugular intrahepatic porto-systemic shunt (TIPS) was not possible due to portal vein occlusion, so he underwent EUS-guided cyanoacrylate glue a second time.
Literature review:
Ectopic varices are rare, contributing to 1–5% of all variceal bleeding, of which 17% is from duodenal varices. Duodenal variceal hemorrhage can lead to hemorrhagic shock, and is potentially life threatening, with quoted mortality rates of 40%. Unfortunately, duodenal varices can be difficult to identify. Diagnosis is often delayed due to a combination of lower awareness and endoscopic challenges given the unusual serosal and submucosal location.
Evidence-based guidelines for the management of ectopic varices are limited. For this reason, our current management strategies rely heavily on local expertise. Splanchnic vasoconstrictor medication, endoscopic ligation, EUS guided gluing, interventional radiology guided embolization, TIPS, balloon retrograde transvenous obliteration and surgical shunts are potential therapeutic options to manage the acutely bleeding varix. Following a variceal bleed, liver transplantation should be considered in eligible patients with no other contraindications.

Conclusions
Duodenal varices are a rare, potentially fatal, and underrecognized cause of gastrointestinal bleeding in patients with portal hypertension. Definitive therapy currently relies upon local expertise in the absence of clear guideline-based therapy.

Funding Agencies
None
A184 NON-CIRRHOTIC HYPERAMMONEMIA SECONDARY TO EXTRAHEPATIC PORTOSYSTEMIC VENOUS SHUNT PRESENTING AS A CONGNITIVE DYSFUNCTION: A CASE REPORT AND LITERATURE REVIEW
Authors: Abdel Moaein T , Ilnyckyj A , Bhangoo S 
Published: February 2020

Abstract

Background
Hyperammonemia secondary to liver disease is a very common cause of hepatic encephalopathy (HE) and it is easily recognized in patients with advanced liver disease. Non-cirrhotic causes of hyperammonemia are rare, particularly extrahepatic portosystemic venous shunts (EPS). The majority of these shunts are between a mesenteric vein and the inferior vena cava. We report a case of a non-cirrhotic hyperammonemia secondary to a shunt between the superior mesenteric vein (SMV) and the right renal vein (RRV) that presented with encephalopathy. Diagnosis was delayed due to lack of awareness of non-cirrhotic hyperammonemia underscoring the importance of measuring ammonia in all patients presenting with encephalopathic symptoms irrespective of their liver function.

Aims
To report our experience with a patient with unexplained cognitive dysfunction that was eventually attributed to hyperammonemia secondary to a rare non-cirrhotic portosystemic shunt. Also, we discuss the differential diagnoses of non-cirrhotic hyperammonemia and the pathophysiology, classification and diagnosis of spontaneous portosystemic shunts.

Methods
A retrospective chart review

Results
A 57-year-old woman with longstanding essential tremors on topiramate presented with a 30-month history of recurrent disabling episodes of unexplained “zoning out”. Her neurologists undertook extensive investigations which excluded primary neurological conditions. These episodes persisted despite discontinuation of topiramate, treatment of urinary tract infection (UTI) and continuing daily prophylactic antibiotics for recurrent UTIs as presumed etiologies. Due to her unexplained and disabling symptoms she was referred to an internist.
During further evaluation, ammonia level was measured for first time, in the absence of any obvious features of chronic liver disease, and the level was strikingly elevated 152uml/l. Hence, an abdominal CT was obtained and revealed a prominent shunt between SMV and RRV.
The patient was diagnosed with non-cirrhotic hyperammonemia secondary to EPS. She is currently stable on lactulose and rifaximin with a drop in her ammonia level to 63uml/l, and an interventional radiological procedure is being considered.

Conclusions
While hyperammonemia is most commonly related to liver failure, our case highlights the importance of awareness of non-cirrhotic hyperammonemia. Any unexplained change in level of consciousness, cognition and/or behavior merits measurement of serum ammonia irrespective of clinical liver status.

Funding Agencies
None
A187 CHOLESTATIC LIVER DISEASE AND BRAIN DYSFUNCTION: ROLE OF THE ARYL HYDROCARBON RECEPTOR
Authors: Mathews A J , Vicentini F , Swain L , Swain M , Sharkey K A 
Published: February 2020

Abstract

Background
Cholestatic liver disease is associated with immune-mediated inflammatory liver injury. This disorder is also associated with brain dysfunction and behavioural changes, notably fatigue, depression and social withdrawal. The mechanisms leading to these central nervous system abnormalities are unknown, however, they are associated with neuroinflammation. Microglia and astrocytes are two glial populations that play key roles in neuroinflammation. Activated glia display morphological changes, secrete cytokines, and mediate electrophysiological changes, altering the normal functioning of the brain. The aryl hydrocarbon receptor (AhR) is a transcription factor involved in the immune response. AhR is present on glia and its’ activation has been shown to reduce neuroinflammation. The role of the AhR in cholestatic liver disease has yet to be examined.

Aims
To study the function of the AhR in a model of cholestic liver disease. We will test the hypothesis that activation of AhR in the brain will reduce neuroinflammation and behavioral deficits observed in cholestatic mice.

Methods
Male C57Bl/6J mice had cholestasis induced by bile duct ligation (BDL); comparisons were made to sham-operated controls. Mice were tested for social interaction with a 4-week old juvenile in their home cage and the number of social interaction attempts quantified. Next, mice were euthanized, brains were removed and processed for immunohistochemistry. Brain sections were stained for markers of microglia (IBA-1) and astrocytes (GFAP). Microglia were counted and astrocyte activation was qualitatively assessed. PCR was used to quantify gene expression of AhR and its downstream gene targets (eg. CYP1A1) in mice that recived treatment with beta-napthoflavone (BNF), an AhR agonist, or in vehicle treated controls.

Results
BDL mice made significantly fewer attempts to interact with the juvenile as compared to controls (P&lt;0.05). We also observed a significant increase in IBA-1 immunoreactive cell numbers in both the CA1 region of the hippocampus and the hypothalamic paraventricular nucleus (PVN, P&lt;0.05). BDL mice also displayed marked increases in GFAP+ staining in the PVN, but not the CA1, in contrast to sham controls. Lastly, we found that BNF significantly upregulated CYP1A1 (P&lt;0.05) in the liver and prefrontal cortex of mice. We are currently examining whether BNF can reduce neuroinflammation and improve decreased social interaction in cholestatic mice.

Conclusions
Cholestatic liver damage was associated with impaired social behavior. Further, glial activation, an indicator of neuroinflammation was increased in components of the limbic system associated with the response to stress, learning, and memory. Future experiments will address whether activation of the AhR will ameliorate neuroinflammation and behavioral changes observed in mice with cholestatic liver injury.

Funding Agencies
CCC, CIHR
A196 INCIDENCE OF PEDIATRIC EOSINOPHILIC ESOPHAGITIS IN EDMONTON ZONE AND RISK OF STRICTURING AT DIAGNOSIS
Authors: Burnett D , Persad R , Huynh H Q 
Published: February 2020

Abstract

Background
Eosinophilic esophagitis (EoE) is a common cause of esophageal dysfunction in children. A subset of children have a more severe phenotype of EoE, complicated by esophageal stricturing. Limited work has been done to characterize this phenotype.

Aims
To determine the incidence of EoE, and the frequency of esophageal stricturing in pediatric EoE.

Methods
We retrospectively identified all new cases of EoE at the Stollery Children’s Hospital from 2015–2018 using esophageal biopsy reports for the province of Alberta (CoPath database), EoE clinic lists and an OR database for esophageal dilatation at the Stollery. Electronic medical records (EMR) were reviewed to confirm EoE diagnosis. For each confirmed case, clinical data was captured from the outpatient EMR and gastroscopy/pathology reports. A review of peri-endoscopy OR/nursing charts was performed on a subset of patients (n=75) to capture scope adverse event. Statistics Canada 2016 census data was used to calculate incidence rates.

Results
185 new cases of EoE were diagnosed at our center during the study period (see table). For patients &lt; 15 years old living in Edmonton zone (n=73), the incidence over the 4 years was 11.1 cases per 100,000 person years {8.7 (0–4 year-old), 7.6 (5–9 year old), and 18.1 (10–14 year old)}. There was limited variation in incidence in the 4 years (9.1–12.1 per 100,000 person years). 8 of 185 (4%) patients had endoscopically confirmed esophageal strictures, 4 of which required mechanical dilation (mean 3.75 dilations per patient, range 1–6). 11/185 (5.9%) patients had more subtle signs of esophageal narrowing, but no strictures. No perforations or episodes of significant bleeding were reported in peri-endoscopy charts reviewed for 239 gastroscopes, including 16 dilations. Pain was reported after 15% of all scopes, including 50% of the 28 scopes with strictures and 63% of the 16 scopes involving dilations.

Conclusions
Edmonton zone has one of the highest incidences of EoE reported in children. In this cohort, 4% had esophageal stricture (half required dilatation) and 5.9% had more subtle narrowing. Patients with strictures were older, had more frequent food impaction and longer duration of symptoms (Table). This data will be included in an ongoing multicenter case-control study across Canada.

Funding Agencies
CAGWomen and Children’s Health Research Institute (Univ. Alberta)
A204 ANALYSIS AND CHARACTERIZATION OF THE EXCRETED AND SECRETED PRODUCTS OF PARASITIC HELMINTHS AS IMMUNOMODULATORS OF INFLAMMATORY BOWEL DISEASE
Authors: Siciliani E A , Arai T , Geary T , Lopes F , Jardim A 
Published: February 2020

Abstract

Background
Parasitic helminths are known for their exceptional ability to modulate the host immune response in order to favour their survival. The excretory/secretory products (ESP), from Trichuris and Ascaris species are of keen interest for inflammatory bowel disease (IBD). Crohn’s disease and ulcerative colitis patients have benefitted from the administration of ova of T. suis in clinical trials, whereby symptoms were remediated through the ingestion of parasite ova, which subsequently hatch in the intestine. Our previous work has demonstrated the ability of T. suis ESP to downregulate secretion of inflammatory cytokines (TNF-α, IL-12) and increase the secretion of anti-inflammatory cytokines (IL-10) in murine bone marrow-derived macrophages.

Aims
This research aims to unveil the mechanisms of immune modulation by parasitic helminths in the context of IBD. We aim to characterize the cellular response in vitro, as well as the systemic response in vivo, in order to better characterize the scope of immune modulation that occurs with treatment.

Methods
Human peripheral blood mononuclear cell (PBMC) monocytes were purified and treated with helminth-derived products. The products were removed, and fresh media was added containing lipopolysaccharide (LPS) to stimulate cells. Supernatants were collected for cytokine analysis and cells were lysed and frozen.
Mice were given 3% DSS or regular water for five days, and subsequently administered treatment with helminth-derived products, or a PBS control, once daily by intraperitoneal injection for 3–4 days. Weights were measured daily. On day 9 mice were sacrificed, colons lengths were measured, and spleens were collected for further analysis.

Results
We found that human PBMC monocytes treated with the ESP from T. suis and A. suum had decreased secretion of inflammatory cytokines (TNFα) and increased secretion of anti-inflammatory cytokines (IL-10).
Additionally, we found that heminth products from A. suum had the ability to reverse the symptoms of weight loss and colon shrinking in DSS-mice compared to the control. Specifically, mice with DSS-induced colitis treated with metabolites increased their weight more than the PBS control (P &lt; 0.0001) and had a longer colon compared to the PBS control (P &lt; 0.001).

Conclusions
Taken together, these data generate an interest for intestinal helminth products as immunomodulators regarding treatment for patients suffering from inflammatory bowel disease (IBD).

Funding Agencies
NSERC and FRQNT
A206 SUSCEPTIBILITY OF HNF4AΔIEC MICE TO SALMONELLA INFECTIONS
Authors: Pupo Gómez D , Reyes-Nicolas V , Marrero G , Perreault N , Menendez A , Boudreau F 
Published: February 2020

Abstract

Background
Inflammatory bowel diseases (IBD) are a group of chronic disorders that affect more than 233 000 Canadians and for which there is not yet an effective treatment. In addition, IBD is a multifactorial disease depending on genetic, immune and environmental dysregulations. The gastrointestinal epithelium plays an important role as a barrier that protects against antigens and bacterial products that are in the lumen. It is well recognized that a defect in the integrity of the barrier and its functions may be involved in the development of these diseases. On the other hand, our laboratory has shown that the conditional deletion of HNF4alpha nuclear receptor (Hnf4a) in the intestinal epithelium of mice can lead to the development of chronic inflammation of the intestine. However, the impact of the loss of this transcriptional factor on the epithelial barrier is still controversial.

Aims
To evaluate the impact of Hnf4a deletion on the epithelial barrier during bacterial infections.

Methods
We used a tamoxifen-inducible Cre-loxP system to delete the Hnf4a gene in the intestinal epithelium of 2-month-old mice, that were then infected with an attenuated strain of Salmonella typhimurium (SB1003) during 4 days. S. typhimurium loads were determined in cecum and colon content, and in liver, spleen tissues by plating homogenates on LB agar supplemented with streptomycin. Also, histological examinations and gene expression of selected targets were assessed between mutant (Hnf4aΔIEC) and control mice.

Results
The tamoxifen-inducible Cre-loxP system was able to delete intestinal Hnf4a gene expression with almost 100% of efficacy. Analysis by qPCR showed that the infection caused significant changes on the response of different infection responsive components (Relmβ, Muc2 and IL-33) in mutant mice. In addition, morphological analyses revealed an increase in the infiltration of immune cells and the number of goblets cells, indicative of an increase in the susceptibility to Salmonella typhimurium (SB1003) infection of the mutant mice.

Conclusions
Altogether, our results suggest that Hnf4a could be involved or play an important role as a modulator of the intestinal epithelial barrier function during Salmonella typhimurium (SB1003) infection. Therefore, understanding the mechanisms involved in this process could allow the development of better therapies for IBD.

Funding Agencies
CIHR