Necrotizing Esophagitis: A Big Squeeze?

Necrotizing esophagitis is rare and poorly understood. The etiologies reported in what little has been published (i.e., gastroesophageal reflux exacerbated by gastric outlet obstruction and low-flow ischemia) seem somewhat simplistic and lack any direct evidence. The following paper illustrates a recent clinical case while laying out arguments supporting esophageal spasm as a possible contributing factor.

Increasing Prevalence and Direct Health Care Cost of Inflammatory Bowel Disease Among Adults: A Population-Based Study From a Western Canadian Province

Objectives Our study aimed to calculate the prevalence and estimate the direct health care costs of inflammatory bowel disease (IBD), and test if trends in the prevalence and direct health care costs of IBD increased over two decades in the province of Saskatchewan, Canada. Methods We conducted a retrospective population-based cohort study using administrative health data of Saskatchewan between 1999/2000 and 2016/2017 fiscal years. A validated case definition was used to identify prevalent IBD cases. Direct health care costs were estimated in 2013/2014 Canadian dollars. Generalized linear models with generalized estimating equations tested the trend. Annual prevalence rates and direct health care costs were estimated along with their 95% confidence intervals (95%CI). Results In 2016/2017, 6468 IBD cases were observed in our cohort; Crohn’s disease: 3663 (56.6%), ulcerative colitis: 2805 (43.4%). The prevalence of IBD increased from 341/100,000 (95%CI 340 to 341) in 1999/2000 to 664/100,000 (95%CI 663 to 665) population in 2016/2017, resulting in a 3.3% (95%CI 2.4 to 4.3) average annual increase. The estimated average health care cost for each IBD patient increased from $1879 (95%CI 1686 to 2093) in 1999/2000 to $7185 (95%CI 6733 to 7668) in 2016/2017, corresponding to an average annual increase of 9.5% (95%CI 8.9 to 10.1). Conclusions Our results provide relevant information and analysis on the burden of IBD in Saskatchewan. The evidence of the constant increasing prevalence and health care cost trends of IBD needs to be recognized by health care decision-makers to promote cost-effective health care policies at provincial and national levels and respond to the needs of patients living with IBD.

A45 A NOVEL PH-SENSITIVE OPIOID ANALGESIC THAT SELECTIVELY INHIBITS NOCICEPTION IN DSS-INDUCED COLITIS

Background Opioid drugs are used to treat pain in inflammatory bowel disease (IBD) but their side effects can cause serious morbidity. Therefore, we tested a novel opioid analgesic, ±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenylpropionamide (NFEPP) which selectively activates peripheral µ-opioid receptors at acidic pH, as occurs in inflamed tissue. Aims Evaluate whether NFEPP causes analgesia in the inflamed colon of DSS-colitis mice using both in vitro and in vivo techniques. Methods To measure the visceral motor reflex (VMR) in response to colorectal distention, EMG electrodes connected to a telemetric transmitter were implanted in mice (c57BL/6), after 10 days recovery acute dextran sodium sulfate (DSS) colitis was induced (5 days 2.5% DSS, 2 days water). VMR was measured 30 min after s.c. injection of vehicle or 0.2 mg/kg of NFEPP or fentanyl. Motility was assessed by fecal pellet count 1 hour after NFEPP. Colonic tissue pH was evaluated using the SNARF-4F-5 carboxylic acid probe. Excitability of mouse dorsal root ganglia (DRG) neurons was measured by recording the rheobase (minimum input current to fire an action potential) after superfusion of NFEPP (300 nM, 10 min) or vehicle at pH 6.5 or 7.4. Colonic afferent nerve responses to probing with a von Frey filament (1 gm) were examined before and after exposure to NFEPP (300 nM, 5 min superfusion) at pH 6.5 and 7.4 respectively. The data was analyzed with Welch’s t-test, 1- or 2-way ANOVA with post hoc Dunnett or Bonferroni or Tukey’s test. Results NFEPP significantly inhibited the VMR in response to distension in mice with colitis compared to vehicle (decreased response by 65%, P<0.001). NFEPP had no effect in control mice. Conversely, fentanyl caused a similar decreased response in both groups (DSS 79% and control 67%, P<0.001). Pelleting was not affected by NFEPP injection in either group compared to vehicle. The pH measurement revealed a more acidic environment in DSS colonic tissue (ΔpH0.37±0.14, P<0.05) compared to controls. In patch-clamp studies, NFEPP decreased DRG excitability at pH 6.5 compared to the baseline and vehicle (increased rheobase 53.84%, P<0.01 and 36.36%, P<0.05 respectively) but had no effect at pH 7.4. In colonic afferent nerve recordings, NFEPP significantly attenuated afferent responses (28.9% P<0.01) to probing at pH 6.5 but also had no effect at pH 7.4. Conclusions This pH-selective opioid agonist significantly inhibits pain at the site of inflammation where the tissue pH is acidic but has no effect in tissues where the pH is in the physiological range. Thus, NFEPP could be an effective opioid analgesic in IBD while being devoid of any unwanted side effects. Funding Agencies CCC

A131 POINT OF CARE ULTRASOUND CHANGES THE NEEDLE INSERTION LOCATION FROM AN ANATOMICALLY LANDMARKED SITE DURING BEDSIDE PARACENTESIS.

Background Paracentesis is a bedside procedure to obtain ascitic fluid from the peritoneum. It is traditionally performed using anatomic landmarking and percussion to ascertain a safe drainage site. The serious complication rate has been reported as less than 2%. Point-of-care ultrasound (POCUS) has been adopted into education and clinical use and has been shown to improve the safety of certain procedures such as central line insertion and thoracentesis. However, the evidence supporting its use is limited. Aims We aimed to assess if POCUS would yield a user-preferred site for needle insertion compared to conventional landmarking, defined as a >5cm change in location. Methods Adult patients under the care of gastroenterology or general internal medicine at Kingston Health Sciences Centre undergoing paracentesis were consecutively enrolled between January and September of 2020. Physicians performing the procedure were enrolled based on availability. An anatomic site was selected 4cm superiorly and 2-4cm medially to the anterior superior ileac spine and confirmed with dullness to percussion. POCUS was then employed to determine if there was an alternative user-preferred site. Patient and operator demographic data and procedure-related information were collected. Results A total of 30 individual patients and 24 operators were enrolled, comprising 45 unique procedure combinations. Operators were primarily in their PGY 1 and 2 years of training (33% and 31% respectively). Per procedure, patients mean age was 61, and most of the ascites was due to cirrhosis (84%) predominantly due to EtOH (47%) and NAFLD (34%). As per indication, 29% of procedures were for diagnostic purposes alone. In total, users primarily preferred the POCUS site which resulted in a change in needle insertion site >5cm from the anatomic site in 69% of cases. The average depth of fluid was greater at the POCUS site vs. the anatomic site (5.4cm+/-2.8 vs 3.0cm+/-2.5, p<0.005). On average, POCUS deflected the needle insertion site superiorly and laterally to the anatomic site. Operators listed that per procedure the POCUS site was chosen to avoid adjacent organs (38%), optimize fluid pocket (61%) and due to abdominal wall issues (primarily issues with pannus; 11.5%). Importantly 6 cases were aborted due to a lack of an appropriate fluid pocket, despite clinical and/or prior radiographic evidence of ascites. Conclusions Overall, POCUS changes the needle insertion site from the conventional anatomic site for most procedures, due to user-perceived safety concerns. POCUS also prevented an attempt at paracentesis in 6 cases that were deemed unsafe. Therefore, POCUS plays an important role in bedside paracentesis. This research supports the use of POCUS in paracentesis and argues for continued training with POCUS throughout medical school and residency. Funding Agencies None

A122 WATER EXCHANGE FACILITATES HIGH CECAL INTUBATION RATE FOLLOWING INCOMPLETE COLONOSCOPY

Background Incomplete colonoscopy is a complex problem that negatively affects the success of colon cancer screening programs. Failure to intubate the cecum is associated with a significant risk of missed colorectal cancer and increases costs through missed diagnoses and salvage investigations. Water exchange (WE) colonoscopy is associated with a high rate of patient comfort and cecal intubation (CI) and may be of value in preventing and following up on incomplete colonoscopy. Aims To estimate effectiveness of WE colonoscopy as initial salvage of incomplete colonoscopy. Methods All patients referred to the Kelowna Gastroenterology group for incomplete colonoscopy between Jan 2010 to Dec 2019 were included. Demographic, clinical, procedural, and pathological information were collected via retrospective chart review. Patients underwent WE colonoscopy by a single endoscopist. The outcomes evaluated were CI rate, sedation requirements, and adenoma detection. Results 116 patients met study criteria and underwent WE colonoscopy after a previously failed or incomplete colonoscopy for technical reasons. The mean age was 66 years (range 21–89). 83 (72%) patients were female. 53 (46%) patients had previous abdominal surgery, and 42 (36%) had previous pelvic surgery. 65 (56%) patients had previous bowel disease. 81 (70%) patients had previously incomplete conventional air insufflation (AI) colonoscopy, 9 (8%) patients had previously incomplete WE colonoscopy, and 5 (4%) patients underwent unsuccessful combination of WE and AI colonoscopy. 17 (15%) patients had previously incomplete flexible sigmoidoscopy, and 4 (3%) patients had previously incomplete water immersion colonoscopy. The most common cause of unsuccessful CI was redundant colon (n=39, 34%) followed by strictures/angulations (n=16, 14%). 105 (91%) patients underwent repeat WE colonoscopy only, while 7 (6%) patients had combination WE and AI colonoscopy and 4 (3%) patients had concurrent gastroscopy. CI was successful in 114 (98%) patients and unsuccessful in 2 (2%) patients. 87 (75%) study patients received conscious sedation, 16 (14%) opted for no sedation, and 7 (6%) attempted no sedation then switched to conscious sedation. 5 patients (4%) required general anesthesia. CI was achieved in all 16 unsedated patients. 236 polyps were identified in 79 (68%) patients, 2 (1%) of which were malignant. Conclusions There is no standardized approach to incomplete colonoscopy. In this cohort of patients with previous failed attempt at colonoscopy, WE as a primary technique was associated with a high success rate with minimal need for general anesthesia and a high rate of polyp detection. A significant rate of colon cancer was identified, similar to that seen in general screening populations. Funding Agencies None

A226 INCIDENTAL FINDING OF A LARGE GASTRIC VARIX ASSOCIATED WITH NEONATAL UMBILICAL VEIN CANALIZATION

Results A 41-year old Asian male, who immigrated to Canada many years ago, and who had previously been successfully treated for Helicobacter pylori infection underwent gastroscopy for investigation of dyspepsia. His gastroscopy was normal except for a large subepithelial abnormality that was noted close to the gastroesophageal junction. Routine gastric biopsies from the antrum and body were normal. Subsequent endoscopic ultrasound revealed flow through the anechoic tortuous lesion and confirmed it was a very large isolated gastric varix type 1. Abdominal CT scan revealed chronic occlusion of the portal vein, splenic vein, and the portal confluence with extensive collateralization in the upper abdomen. There was complete cavernous transformation of the portal vein. Of the numerous varices in the upper abdomen, a very large varix drained into the left renal vein and indented into the posterior wall of the fundus of the stomach which accounted for the endoscopic finding. Multiple mesenteric veins were identified that connected to varices adjacent to the inferior aspect of the pancreas and duodenum. Notably, there was no evidence of cirrhosis or chronic pancreatitis. Liver enzymes, albumin, and INR were normal. Further collateral history revealed that he was hospitalized as a neonate for pneumonia with catheterization of the umbilical vein, which is known to be associated with thrombosis of the portal vein. Conclusions Detection of congenital absence of the portal vein (CAPV) is recognized more often due to advances in diagnostic imaging. Radiologically, the absence of the portal vein in CAPV is distinguished from portal vein thrombosis by the lack of venous collaterals or sequalae of portal hypertension, such as ascites or splenomegaly. A more gradual thrombosis of the portal vein may permit collaterals to develop without acute changes and is not equivalent to portal vein aplasia or agenesis as intrahepatic bile ducts are normal. The gold standard for diagnosis of CAPV is histologic absence of the portal vein in the liver on catheter angiography. CAPV is associated with abnormal embryologic development of the portal vein and frequently presents with complications of portal hypertension or portosystemic encephalopathy or the sequalae of venous shunts, hepatic or cardiac abnormalities found on imaging. Our case is an incidentally discovered absence of the portal venous system due to chronic thrombosis with extensive collateralization and an enlarged gastric varix protruding into the proximal stomach. It is well documented that canalization of the umbilical vein in infancy is associated with portal vein thrombosis, with incidences up to 68%. This case highlights the importance of eliciting a childhood hospitalization history in cases of non-cirrhotic portal hypertension. Funding Agencies None

A206 EVOLUTION OF PEDIATRIC AUTOIMMUNE CHOLANGITIS AND PRIMARY SCLEROSING CHOLANGITIS INTO ADULTHOOD

Background The natural history of primary sclerosing cholangitis (PSC) in children seems to differ from PSC in adults. However, studies on this matter have been limited by short follow-up periods and inconsistent classification of patients with autoimmune cholangitis (AIC) (or overlap syndrome). Consequently, it remains unclear if long-term outcomes are affected by the clinical phenotype. Aims The aims of this is study are to describe the long-term evolution of PSC and AIC in a pediatric cohort with extension of follow-up into adulthood and to evaluate the influence of phenotype on clinical outcomes. Methods This is a retrospective study of patients with AIC or PSC followed at CHU-Sainte-Justine, a pediatric referral center in Montreal. All charts between January 1998 and December 2019 were reviewed. Patients were classified as either AIC (duct disease on cholangiography with histological features of autoimmune hepatitis) or PSC (large or small duct disease on cholangiography and/or histology). Extension of follow-up after the age of 18 was done for patients followed at the Centre hospitalier de l’Université de Montréal. Clinical features at diagnosis, response to treatment at one year and liver-related outcomes were compared. Results 40 patients (27 PSC and 13 AIC) were followed for a median time of 71 months (range 2 to 347), with 52.5% followed into adulthood. 70% (28/40) had associated inflammatory bowel disease (IBD) (78% PSC vs 54% AIC; p=0.15). A similar proportion of patients had biopsy-proven significant fibrosis at diagnosis (45% PSC vs 67% AIC; p=0.23). Baseline liver tests were similar in both groups. At diagnosis, all patients were treated with ursodeoxycholic acid. Significantly more patients with AIC (77% AIC vs 30 % PSC; p=0.005) were initially treated with immunosuppressive drugs, without a significant difference in the use of Anti-TNF agents (0% AIC vs 15% PSC; p= 0.12). At one year, 55% (15/27) of patients in the PSC group had normal liver tests versus only 15% (2/13) in the AIC group (p=0.02). During follow-up, more liver-related events (cholangitis, liver transplant and cirrhosis) were reported in the AIC group (HR=3.7 (95% CI: 1.4–10), p=0.01). Abnormal liver tests at one year were a strong predictor of liver-related events during follow-up (HR=8.9(95% CI: 1.2–67.4), p=0.03), while having IBD was not (HR=0.48 (95% CI: 0.15–1.5), p=0.22). 5 patients required liver transplantation with no difference between both groups (8% CAI vs 15% CSP; p=0.53). Conclusions Pediatric patients with AIC and PSC show, at onset, similar stage of liver disease with comparable clinical and biochemical characteristics. However, patients with AIC receive more often immunosuppressive therapy and treatment response is less frequent. AIC is associated with more liver-related events and abnormal liver tests at one year are predictor of bad outcomes. Funding Agencies None

A38 TRPV1 VISCERAL AFFERENTS CONTROL CENTRAL SENSITIZATION IN IBD

Background Long-lasting changes in neural pain circuits precipitate the transition from acute to chronic pain in patients living with inflammatory bowel diseases (IBDs). While significant improvement in IBD therapy has been made to reduce inflammation, a large subset of patients continues to suffer throughout quiescent phases of the disease, suggesting a high level of plasticity in nociceptive circuits during acute phases. The establishment of chronic visceral pain results from neuroplasticity in nociceptors first, then along the entire neural axis, wherein microglia, the resident immune cells of the central nervous system, are critically involved. Our lab has shown that spinal microglia were key in controlling chronic pain state in IBD. Using the Dextran Sodium Sulfate (DSS) model of colitis, we found that microglial G-CSF was able to sensitize colonic nociceptors that express the pain receptor TRPV1. While TRPV1+ nociceptors have been implicated in peripheral sensitization, their contribution to central sensitization via microglia remains unknown. Aims To investigate the role of TRPV1+ visceral afferents in microglial activation and chronic visceral pain. Methods We generated DREADD (Designer Receptors Exclusively Activated by Designer Drugs) mice in which TRPV1 sensory neurons can be inhibited (TRPV1-hM4Di) or activated (TRPV1-hM3Dq) in a time and tissue specific manner using the inert ligand Clozapine-N-Oxide (CNO). To test the inhibition of TRPV1 neurons in DSS-induced colitis, TRPV1-hM4Di mice were treated with DSS 2.5% or water for 7 days and received vehicle or CNO i.p. injection twice daily. To activate TRPV1 visceral afferents, TRPV1-hM3Dq mice received vehicle or CNO daily for 7 days, by oral gavage. After 7 days of treatment, visceral pain was evaluated by colorectal distension and spinal cords tissues were harvested to measure microglial activation. Results Our data validated the nociceptor specific expression and function of the DREADD in TRPV1-Cre mice. Inhibition of TRPV1 visceral afferents in DSS TRPV1-hM4Di mice was able to prevent the colitis-induced microglial activation and thus reduce visceral hypersensitivity. In contrast, activation of TRPV1 visceral afferents in TRPV1-hM3Dq mice was sufficient to drive microglial activation in the absence of colitis. Analysis of the proalgesic mediators derived from activated TRPV1-hM3Dq neurons identified ATP as a key factor of microglial activation. Conclusions Overall, these data provide novel insights into the mechanistic understanding of the gut/brain axis in chronic visceral pain and suggest a role of purinergic signaling that could be harnessed for testing effective therapeutic approaches to relieve pain in IBD patients. Funding Agencies CCCACHRI (Alberta Children’s Hospital Research Institute) and CSM (Cumming School of Medicine) postdoctoral fellowship

A117 PROPOFOL SEDATION DOES NOT IMPROVE MEASURES OF COLONOSCOPY QUALITY – FINDINGS FROM THE SOUTHWEST ONTARIO COLONOSCOPY COHORT

Background The use of propofol during colonoscopy has gained increased popularity due to deeper anesthesia compared to conscious sedation. Prior studies examining the use of propofol sedation during colonoscopy have primarily focused on anesthesia outcomes. Whether propofol sedation is associated with improvements in colonoscopy outcomes is uncertain. Aims The primary outcome was adenoma detection rate (ADR). Secondary outcomes were the detection of any adenoma (conventional adenoma, sessile serrated polyp, and traditional serrated adenoma), sessile serrated polyp detection rate, polyp detection rate, cecal intubation rate, and perforation rate. Methods The Southwest Ontario Colonoscopy cohort consists of all patients who underwent colonoscopy between April 2017 and Oct 2018 at 21 hospitals serving a large geographic area in Southwest Ontario. Procedures performed in patients less than 18 years of age or by endoscopist who perform <50 colonoscopies/year were excluded. Data were collected through a mandatory quality assurance form that was completed by the endoscopist after each procedure. Pathology reports were manually reviewed. Results A total of 46,634 colonoscopies were performed by 75 physicians (37.5% by gastroenterologists, 60% by general surgeons, 2.5% others) of which 16,408 (35.2%) received propofol and 30,226 (64.8%) received conscious sedation (e.g. combination of a benzodiazepine and a narcotic). Patients who received propofol were likely to have a screening indication (49.2% vs 45.5%, p<0.0001), not have a trainee endoscopist present and be performed at a non-academic centre (32.2% vs 44.6%, p<0.0001). Compared to conscious sedation, use of propofol was associated with a lower ADR (24.6% vs. 27.0%, p<0.0001) and detection of any adenoma (27.7% vs. 29.8%, p<0.0001); no difference was observed in the detection ofsessile serrated polyps (5.0% vs. 4.7%, p=0.26), polyp detection rate (41.2% vs 41.2%, p=0.978), cecal intubation rate (97.1% vs. 96.8%, p=0.15) or perforation rate (0.04% vs. 0.06%,p=0.45). On multi-variable analysis, the use of propofol was not significantly associated with any improvement in ADR (RR=0.90, 95% CI 0.74–1.10, p=0.30), detection of any adenoma (RR=0.93, 95% CI 0.75–1.14, p=0.47), sessile serrated polyp detection rate (RR=1.20, 95%CI 0.90–1.60, p=0.22), polyp detection rate (RR=1.00, 95% CI 0.90–1.11, p=0.99), or cecal intubation rate (RR=1.00, 95%CI 0.80–1.26, p=0.99). Conclusions The use of propofol sedation does not improve colonoscopy quality metrics. Funding Agencies None

A75 IMPLEMENTING A CIRRHOSIS ORDER SET: A QUALITATIVE ANALYSIS OF PROVIDER-IDENTIFIED BARRIERS AND FACILITATORS

Background Cirrhosis is the leading cause of mortality and morbidity in individuals with gastrointestinal disease. Multiple care gaps exist for hospitalized patients with cirrhosis, resulting in high rates of re-hospitalization (e.g. 44% at 90 days in Alberta). The Cirrhosis Care Alberta (CCAB) is a 4-year multi-component pragmatic trial with an aim to reduce acute-care utilization by implementing an electronic order set and supporting education across eight hospital sites in Alberta. Aims As part of the pre-implementation evaluation, this qualitative study analyzed data from provider focus groups to identify barriers and facilitators to implementation. Methods We conducted focus groups at eight hospital sites with a total of 54 healthcare providers (3–12 per site). A semi-structured interview guide based upon constructs of the Consolidated Framework for Implementation Research (CFIR) and Normalization Process Theory (NPT) frameworks was used to guide the focus groups. Focus groups were recorded and transcribed verbatim. Data was analyzed thematically and inductively. Results Five major themes emerged across all eight sites: (i) understanding past implementation experiences, (ii) resource challenges, (iii) competing priorities among healthcare providers, (iv) system challenges, and (v) urban versus rural differences. Site-specific barriers included perceived lack of patient flow, time restraints, and concerns about the quality and quantity of past implementation interventions. Facilitators included passionate project champions, and an ample feedback process. Conclusions Focus groups were useful for identifying pre-implementation barriers and facilitators of an electronic orders set. Findings from this study are being refined to address the influence of COVID-19, and the data will be used to inform the intervention roll-out at each of the sites. Funding Agencies Alberta Innovates