bluuebunny/crossref_metadata_2025 huggingface dataset:
A62 CANADIAN POPULATION-BASED EVALUATION OF THE NATURAL HISTORY OF PRIMARY BILIARY CHOLANGITIS OVER THE LAST DECADE
Authors: Azhari H , Swain M , Shaheen A M
Published: February 2020

Background

Few studies have evaluated the epidemiology of primary biliary cirrhosis (PBC) in North America. Ursodeoxycholic acid (URSO) improves outcomes amongst PBC patients.

Aims

Therefore, we undertook this study to determine the epidemiology of PBC in Canada, and impact of URSO on clinical outcomes, two decades after URSO approval in North America.

Methods

We used our previously validated coding algorithm to identify PBC patients in population based administrative databases in the Calgary Health Zone (population ~1.5 million) from 2005–2015. Multiple sources of data including inpatient, ambulatory, physician billing, laboratory, and pharmaceutical were linked. Annual prevalence and incidence were estimated using Poisson regression. Age/sex adjusted rate ratios were calculated. We used Cox regression models to estimate: all-cause mortality, liver transplant and decompensated cirrhosis free survival. In our models, we adjusted for demographic and clinical variables including response to URSO.

Results

During the study period over 11 years, the overall annual age/sex adjusted PBC incidence was 29.5 cases per million (48.3 and 9.9 per million for women and men, respectively). The highest incidence rate was observed among women aged 60–79 (90.9 per million) with an incidence rate ratio of 10.4 (95%: 6.83–15.9) compared to those aged 20–39. While incidence rate remained stable, prevalence rate increased significantly from 242 to 343 cases/ million, between 2005 and 2015 (P<0.01). Prevalence rate was highest at 965 cases/ million amongst women aged 60–79. We identified 299 incident PBC cases with a median follow up of 5.1 years (IQR 2.9–8.3). 87 (29.1%) of these incident cases developed decompensated cirrhosis or HCC, 10 patients (3.4%) underwent liver transplantation, and 44 (14.7%) patients died. The annual mortality rate was 2.9% (95%CI: 2.1- 3.8) compared to 3.4% (2.3–4.9%) a decade ago (P=0.04). The estimated 5-year survival rate was 87.6% (82.6- 91.3). Standardized mortality rate was 3.2 (95%CI: 2.2–4.1). Overall, 25% of our incident cohort were not prescribed URSO. Patients not prescribed URSO were more likely to be male, older age, have normal ALP and had decompensated cirrhosis at diagnosis (P<0.01 for all). Among those who used URSO, response rate was 86%. Response to URSO was an independent predictor of reduced risk of decompensated cirrhosis and liver transplant, and higher survival (aHR: 0.46, 0.29–0.74).

Conclusions

PBC prevalence is increasing in this North American population. While mortality rate decreases in our PBC cohort, survival was suboptimal compared to the general population, mainly due to late presentation at diagnosis. Therefore, better surveillance and early detection of possible PBC patients in the primary care setting are essential to improve PBC outcomes.

Funding Agencies

None
A71 MESOCAVAL SHUNT EMBOLIZATION AS A TREATMENT FOR MEDICALLY REFRACTORY HEPATIC ENCEPHALOPATHY IN A PATIENT WITH NON-DECOMPENSATED CIRRHOSIS
Authors: Gupta S , Wong F , Sniderman K , Ryan S , Tsien C
Published: February 2020

Background

Hepatic encephalopathy (HE) is a common complication of cirrhosis with a spectrum of neuropsychiatric manifestations. In patients with medically refractory HE (i.e. after a trial of Lactulose with or without Rifaximin), it is warranted to investigate and manage underlying spontaneous portosystemic shunts (SPS) as a cause of chronic or recurrent HE in the absence of precipitants.

Aims

Here we present a case report of a patient with non-decompensated cirrhosis who underwent mesocaval shunt embolization as a treatment for medically refractory HE (grade III) in the absence of underlying precipitants.

Methods

The patient’s chart was reviewed and radiological images pre- and post- shunt embolization were obtained. A literature review was performed on the treatment of SPS for HE in cirrhosis.

Results

Mr. H is a 56-year-old man with alcohol-related cirrhosis who was admitted to the hospital with a reduced level of consciousness. On examination he was arousable but nonverbal. Asterixis was observed with no focal neurologic findings. Laboratory, infectious and toxicology results were negative. His MELD-Na score was 11. Computed tomography (CT) of his head and ultrasound of his abdomen were normal. The patient did not improve with lactulose and rifaximin. A CT of his abdomen/pelvis revealed a large SPS arising from the superior mesenteric vein (SMV) to the infrarenal inferior vena cava (IVC). A decision was made to attempt partial occlusion of the shunt. A 22-mm Amplatzer™ Vascular Plug II and two 8mm x 59mm Atrium balloon expandable covered stents were deployed in the right gonadal vein. Partial occlusion was subsequently demonstrated with contrast injection. The patient had gradual improvement of his HE and became independent for his ADLs six months post-procedure.

Conclusions

Between 45–70% of patients with cirrhosis and medically refractory HE have SPS as a result of chronic liver injury and increased portal venous pressures. AASLD guidelines recommend screening for SPS in cirrhotic patients with medically refractory HE or in HE with compensated liver disease. Shunt embolization in patients with MELD < 11 has been shown to reverse chronic or recurrent HE as well as improve hepatic outcomes for at least a two-year follow-up, as shown by a recent multicentre survey done by Laleman et al. Further studies have shown that portosystemic shunt embolization can result in reversal of HE in over 75% of cases. The most frequently encountered shunt in these studies is the splenorenal shunt. Our case, however, offers insight into the less commonly experienced mesocaval shunt, which accounts for only 5% of large SPS. We have shown that mesocaval shunts, when discovered, have the potential for successful treatment with embolization that can lead to reversal and long-term clinical remission of HE.

Funding Agencies

None
A88 EARLY-ONSET GASTRIC POLYPS IN CHILDREN WITH FAMILIAL ADENOMATOUS POLYPOSIS: A CASE SERIES
Authors: Stone J , El-Matary W
Published: February 2020

Background

Familial adenomatous polyposis (FAP) syndrome is a familial inherited autosomal dominant polyposis syndrome which predisposes affected individuals to a significantly increasing risk of colorectal cancer before the age of 30 years. Studies examining the rates of duodenal and gastric neoplasia in patients with FAP are scarce. Recent reports have shown a concerning rise in gastric cancer in Western FAP patients with certain endoscopic features. Current guidelines suggest screening with gastroscopy beginning at the age of 20 to 25 years.

Aims

We report a case series of seven pediatric patients with evidence of early-onset upper gastrointestinal adenomatous polyps.

Methods

A retrospective chart review was performed for all patients diagnosed with FAP between January 2012 and December 2016 in Winnipeg Children’s Hospital which is the only pediatric tertiary-care hospital in Manitoba. A total of seven pediatric patients from 3 different families were enrolled in our case series. The following data were collected: age of diagnosis, gene mutation, time of first screening endoscopy and total number of endoscopies, number of gastric and colonic polyps, pathology results, surgeries and further routine investigations. Descriptive data were then reported on each patient.

Results

Five of seven patients (71.4%) exhibited maternal inheritance of the APC gene mutation. The mean age of diagnosis was 5.3 years (SE 2.4, range 2–9 years) with male predominance (n=5, 71.4%). Mean age at first colonoscopy was 9.8 years (SE 2.05; range 6.6–11.9) and 9.9 years (SE 1.88; range 6.6–11.9 years) at first gastroscopy. Five (71.4%) patients had evidence of gastric polyps and three (43%) had evidence of duodenal polyps before the age of 14 years. All patients showed an increasing burden of gastric polyposis with age. Tubular adenomas were seen in all patients who developed >50 gastric polyps (n=5), two with low-grade dysplasia diagnosed at the ages of 11 and 15 year. One patient with duodenal polyps showed tubular adenomatous changes at the age of 13.6 years. Capsule endoscopy was performed in all patients and none showed any small bowel polyposis beyond the duodenum. All seven patients had colonic tubular adenomas, two with low-grade dysplasia (at ages of 14 and 15 years) and only one without polyps at the initiation of endoscopic screening. No patients underwent surgery prior to age 15 years.

Conclusions

The presence of gastric and duodenal polyps in pediatric patients with FAP is not uncommon and may be underestimated. Early screening gastroscopy with gastric and duodenal biopsies should be considered at a younger age than what has currently been recommended.

Funding Agencies

None
A89 IMPLEMENTING ENDOSCOPIC SUBMUCOSAL DISSECTION IN A WESTERN CANADIAN SETTING: OUTCOMES, LEARNING CURVE AND LOGISTICAL CONSIDERATIONS
Authors: Trasolini R , Zhao B , Chahal D , Lam E
Published: February 2020

Background

Endoscopic submucosal dissection (ESD) is an advanced resection technique for large gastrointestinal lesions. ESD was developed in Japan and is popular in countries with gastric cancer screening and a high incidence of gastric cancer. ESD has benefits over endoscopic mucosal resection (EMR) such as increased complete resection, en bloc resection and lower recurrence. However, ESD is a longer procedure and is difficult to master in countries with low incidence of early gastric neoplasia which is the ideal anatomic location for learning. There is increasing interest in using ESD techniques including hybrid ESD/EMR in western centers. Barriers include procedure time, perforation risk and challenges accumulating sufficient experience.

Aims

To present our experience implementing an ESD program in British Columbia including outcomes and logistical considerations of interest.

Methods

All ESD procedures since implementation of the program in May 2015 to July 2019 were included. Descriptive statistics and performance indicators over time are reported. All procedures were performed by a staff endoscopist after specialized training. Procedures were performed at two hospitals in British Columbia. Cases were referred from endoscopists and were assessed with dedicated endoscopy with or without endoscopic ultrasound prior to booking ESD.

Results

40 procedures were performed, though only one procedure was performed in the first year (Mean age 70, 67.5% male). ASA class ranged from 1–4 (mean 2.08). 22 lesions were gastric, 13 were rectal, with the remainder throughout the colon. Mean lesion size was 25mm in maximum dimension (interquartile range 15-30mm). 18 procedures were performed under general anesthesia and the remainder using procedural sedation. Total surgical time ranged from 22 to 398 minutes. Mean surgical time was 104 minutes, or 126 minutes including anesthesia. 50% of procedures were performed using hybrid ESD/EMR technique. R0 resection rate across all cases was 68% (60% for hybrid procedures, 80% for strict ESD). En bloc resection rate was 60%. Recurrence rate was 10%. Complication rate was 7.5% all were post-procedure bleeds requiring hospitalization. No perforations occurred. 3 patients required surgery for incomplete resection or invasive cancer on pathology, 3 required repeat endoscopic resection. Surgical time per cm of lesion improved significantly from the first 10 cases to the last 10 (time per cm resected 75 min to 32 min p<0.006).

Conclusions

ESD is an effective therapy for GI neoplasia. ESD is feasible in a Canadian setting. Hybrid techniques tend to be faster though at the expense of R0 resection. Patient centered outcomes in this sample are favorable and comparable to large ESD series. Monitoring of ESD quality is critical for comparison with standard of care as experience with ESD in Canada grows.

Funding Agencies

None
A92 DOSE ESCALATION STUDY OF CYBERKNIFE® BOOST IN UNRESECTABLE LOCALLY ADVANCED PANCREATIC CANCER
Authors: Quinlan J , Pantarotto J , Dennis K , Chatterjee A
Published: February 2020

Background

Pancreatic cancer is the 4th deadliest cancer in Canada, with an overall 5-year survival of only 6%. Every year, approximately 4000 Canadians are diagnosed with pancreatic cancer, and only 10–15% of these patients have surgically resectable disease. No satisfactory treatment exists for patients with inoperable locally advanced pancreatic carcinoma. The best survival has been achieved using a combination of chemotherapy and radiotherapy. Conventional radiotherapy has inadequate local disease control as the therapeutic radiation dose to the tumour is limited by the sensitivities of surrounding tissues. Stereotactic body radiotherapy (SBRT) is a minimally invasive treatment technique that allows for ultra-high doses of radiation to be delivered to small areas. The CyberKnife® Robotic Radiosurgery System is a radiation unit designed to deliver SBRT. Fiducial markers placed by endoscopic ultrasound help direct the radiotherapy. It is hypothesized that a higher overall dose of radiation will result in higher rates of local control, and potentially improved survival.

Aims

The goal of this study is to establish the safety and feasibility of using stereotactic body radiotherapy boost technique via CyberKnife in treating unresectable locally advanced pancreatic cancer, as well as to determine the maximal tolerable radiation dose (MTD) of the SBRT boost that can be safely delivered.

Methods

This is a prospective single-arm, single-institution phase I Time-to-event Continual Reassessment Methodology (TITE-CRM) radiation dose escalation trial. This study enrolled patients aged 18–84 with pathologically confirmed pancreatic cancer who were determined to have surgically unresectable disease, with an ECOG ≤2. These patients were treated with SBRT prior to starting conventional radiotherapy, which consisted of a total dose of 45 Gy in 25 fractions over 5 weeks.

Results

Between 2012 and 2018, a total of 11 patients met the eligibility criteria of this study. Their ages ranged from 61 to 84 with a mean of 71.5 years, and they were 64% (7/11) male. At the time of this analysis, 10 of the 11 patients had passed away. The mean and median survival times were 413 days and 313 days, respectively. Three of the patients had significant complications attributed to the radiotherapy, 2 gastric outlet obstructions and 1 deep duodenal ulcer. The doses used ranged from 21 Gy in 3 fractions to 50 Gy in 5 fractions.

Conclusions

This phase 1, single arm study demonstrates that stereotactic body radiotherapy in the treatment of locally advanced, unresectable pancreatic cancer is technically feasible. When combined with conventional radiotherapy, this therapy is generally well tolerated, and can effectively deliver higher doses of radiation to pancreatic malignancies. Doses up to 50 Gy in 5 fractions were tolerated, with the most common dose being 21 Gy in 3 fractions.

Funding Agencies

National Pancreatic Cancer Canada Foundation
A94 RECURRENT HEPATOCELLULAR CARCINOMA: EVALUATION OF 8 POST-TRANSPLANT SCORING SYSTEMS
Authors: Aziz S , Qumosani K , Teriaky A
Published: February 2020

Background

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation is a major cause of morbidity and mortality. It is well known that there is a discordance between pre-transplant imaging and post-transplant pathology that affect risk of recurrence. Several risk assessment tools have been developed, although to date, there is no widely accepted tool to predict HCC recurrence.

Aims

The aim of the current study is to determine which pathologic risk assessment score has the best predicative ability.

Methods

We retrospectively evaluated 152 patients over a twelve-year period that underwent liver transplantation for HCC. Using explanted pathology reports, each patient was stratified according to the pathologic risk score and followed over time for HCC recurrence. We evaluated eight pathologic risk scores and determined predictive ability by assessing the area under the receiver operating characteristic curve (AUROC).

Results

Out of 152 consecutive liver transplants for HCC, recurrence occurred in 21 patients (14%) with a mean follow-up of 59.5 months. 54% of patients were within Milan criteria prior to transplant. According to explant pathology, microvascular invasion was seen in 16% of patients, with majority of the tumors being moderately differentiated (48%), tumor size ≥ 3cm (52%), and 26% of tumors in both lobes of the liver. Preliminary data suggests that the Parfitt et. al score has the best predictive ability, with 60% of recurrence occurring in those considered high-risk. Further assessment via AUROC will be required to confirm the preliminary data.

Conclusions

Preliminary data suggests the Parfitt et al. score may have the best predictive ability to detect recurrence. This risk assessment tool can help tailor a surveillance strategy for early detection or early adjuvant therapy to improve long-term survival.

Funding Agencies

None
A129 THE VALUE OF REPEAT MANOMETRIC TESTING
Authors: Pandey A , Liu A , Buresi M C , Gupta M , Nasser Y , Curley M , Li D Y , Andrews C N , Woo M
Published: February 2020

Background

While motility disorders may evolve over time, there is scant guidance around the role of repeat high-resolution esophageal manometry (HRM). Given the invasive nature of HRM and the implications on financial cost and patient discomfort, it is obvious that the emphasis should be on minimizing unnecessary repeat examinations. However, there are no recommendations around indications or timing of repeat HRM.

Aims

We aimed to determine the outcomes in patients who underwent repeat manometry and look for predictors of progression to achalasia or major motility disorder.

Methods

Consecutive reports from HRM studies performed between Aug 2013 – May 2017 were retrospectively analyzed. All patients with ≥ 2 HRM studies were included. Studies without a Chicago classification diagnosis were excluded. Chi-squared analysis was performed to determine if initial HRM diagnosis was associated with change in diagnosis on follow-up HRM. Initial and follow-up manometric parameters were compared with paired T-tests. Binary logistic regression analysis was performed to look for predictors of progression to achalasia or major motility disorder.

Results

134 patients underwent ≥ 2 HRM studies. Initial diagnoses were IEM (45 patients [33.6%], EGJOO (34 [25.4%], absent peristalsis (18 [13.4%], achalasia (11 [8.2%], DES (4 [3.0%]), and JH (3 [2.2%]; 29 (14.2%) of patients had a normal HRM. 109 (81.3%) patients underwent 2 HRM, 18 (13.4%) 3 HRM, 4 (3%) 4 HRM, and 3 (2.2%) 5 HRM.

The final follow-up HRM occurred after a median 496 [80 – 1823] days. 72 (53.7%) of patients had no change from their initial diagnosis. Patients with an initial diagnosis of DES were significantly more likely to have a change in diagnosis on the final follow-up (3 normal:1 IEM) (p = .043). No other classes reached significance. Patients with IEM had a significantly higher mean DCI (395.1 [0 - 3248] vs 790.8 [0 – 10715.0], p = .006) and IRP (4.5 [-10.4 – 14.2] vs [6.6 [-6.2 – 21.0], p = .017) on their follow-up HRM.

4 patients without achalasia (3 EGJOO:1 IEM) on their index HRM had a diagnosis of achalasia on their final HRM. The median IRP in non-achalasia patients with a diagnosis of achalasia on final HRM (22.3 [8.4 – 30.7] was significantly higher than those without a diagnosis of achalasia on final HRM (6.6 [-10.4 – 39.8]) (p = .013); however no manometric criteria or initial HRM diagnoses predicted progression to achalasia or major motility disorder on binary logistic regression analysis.

Conclusions

In most patients, repeat manometry did not change the manometric diagnosis. Patients with DES were significantly likely to have their diagnosis change with repeat HRM, and most of these patients had normalization of their HRM. Manometric parameters in IEM appear to improve over time. This finding could reflect interval therapy, or shed some light on the natural history of this disease.

Funding Agencies

None
A132 SMOOTH MUSCLE BIOPSIES FROM POEM PROCEDURES FOR ACHALASIA SHOW LACK OF FUNCTIONAL INNERVATION
Authors: Rodrigues D , Lourenssen S , Bechara R , Blennerhassett M G
Published: February 2020

Background

Idiopathic achalasia is a disease of the esophagus causing impaired peristalsis and absent lower esophageal sphincter relaxation. The etiopathogenesis of the disease is unclear but most histopathologic studies from surgical resections show an absence of nitric oxide-producing neurons in the myenteric plexus. The peroral endoscopic myotomy (POEM) procedure has evolved in the last decade to treat achalasia and has provided a unique way to sample diseased tissue from an otherwise inaccessible tissue compartment.

Aims

To study the effects of achalasia on innervation of smooth muscle and smooth muscle phenotype.

Methods

Patients with a diagnosis of achalasia based on high resolution manometry undergoing a POEM at Kingston general hospital were approached for enrollment between June 2017 to September 2018. Demographic information including age, symptom duration, previous treatments, and Eckhardt score was collected. Intraoperatively, biopsies of the circular smooth muscle (CSM) layer were taken at the proximal and distal extents of the myotomy and placed in formalin. Tissue was embedded in wax, sectioned and stained using immunocytochemistry (ICC) for neuronal, axonal and smooth muscle cell markers. This was compared to control tissue from patients undergoing gastroesophagectomy for adjacent malignancy.

Results

Control tissue from 3 separate esophagectomies were obtained. Samples were obtained from a total of 25 patients (13 males), with a median age of 50 (IQR 38–67). Most patients had Type 2 achalasia (19 [76%]) followed by Type 1 and 3 (2, [8%] respectively). Two cases had conflicting manometric findings. The median duration of symptoms was 3 years (IQR 1.5–10.5) and the median Eckhardt score was 6.5 (IQR 5–9). In sample tissues, no neuronal cell bodies were detected in the CSM layer. ICC for the axonal marker PGP9.5 showed that CSM of achalasia samples were almost completely devoid of axon structure, independent of the subtype of achalasia, compared to abundant axon presence in control tissues. In parallel, ICC showed that cholinergic (ChAT) or nitrergic (nNOS) axonal subtypes were absent in biopsy CSM while abundant in controls. CSM cells displayed hypertrophy with no detection of proliferation by ICC (KI67) or alterations in the phenotypic marker SM-22.

Conclusions

Preliminary results from advanced immunohistochemical techniques show the absence of functional innervation of the CSM layer of all patients with achalasia. This is characterized by a depleted excitatory and inhibitory axon population. Further studies are focused on defining differences in smooth muscle phenotype and the presence or absence of inflammatory cells within the CSM.

Funding Agencies

None
A134 RATES OF PARENTERAL NUTRITION-ASSOCIATED CHOLESTASIS/LIVER DISEASE AND GROWTH PRE- AND POST-SMOFLIPID INTRODUCTION IN NEONATES AND INFANTS WITH INTESTINAL FAILURE
Authors: Tyminski N , Hudson A , Turner J , Silverman J
Published: February 2020

Background

Parenteral nutrition (PN) is essential for survival in infants with intestinal failure (IF). PN-associated cholestasis (PNAC) and liver disease (PNALD) are life-threatening complications of long-term PN use. SMOFlipid (soybean oil, medium-chain triglycerides, olive oil, and fish oil) has recently been approved as an off-label alternative to the conventional soy-based lipid emulsion (Intralipid). It is thought to have anti-cholestatic properties due to its more diverse lipid composition. Due to its’ recent approval in Canada (2013) and the USA (2016), data remains sparse.

Aims

We aim to determine if infants with IF receiving SMOFlipid had significantly lower rates of PNAC and improved growth compared to those receiving Intralipid.

Methods

All patients (≤1 year old at start of PN therapy) who received PN of any duration at two tertiary pediatric hospitals in Edmonton (2010–2018) were identified from the shared pharmacy database. Those with IF who received one type of PN continuously for ≥6 weeks total were included. Individuals with an initial serum conjugated bilirubin >50 µmol/L and/or who had PN interruptions >5 days were excluded. Data on liver parameters, growth, and complications were collected. Non-parametric tests (Mann-Whitney U test for continuous variables and χ2 test for categorical variables) were used to compare PNAC/PNALD (serum conjugated bilirubin >34umol/L during PN) and growth (weight/length/head circumference z-scores) between SMOFlipid and Intralipid.

Results

1777 patients were reviewed; 40 infants (55% male), median age 4 weeks (range 0–48 weeks) at the time of PN initiation, met the inclusion criteria. Reasons for exclusion (n=1737) were receiving PN <6 weeks total (n=1485), duplicate patients (n=154), receiving multiple types of PN with each less than 6 weeks total (n=62), an initial serum conjugated bilirubin >50umol/L (n=21), more than 5 consecutive days off of PN (n=12), and older than 1 year old at time of PN initiation (n=3). Twenty-one patients (53%) received SMOFlipid, 15 (38%) Intralipid, and 4 (10%) Omegaven for ≥6 weeks. The majority (92%) were in an intensive care unit (neonatal or pediatric). No patients were septic when starting PN. Individuals received PN over a median of 7.9 weeks (range 6–27 weeks).

Conclusions

As expected, neonatal onset intestinal failure is rare in Edmonton. In our tertiary pediatric institutions, 2010–2018, SMOFLipid was the predominant lipid choice for infants with intestinal failure, followed by Intralipid. Omegaven was used rarely. This dataset will now allow us to compare the rates of PNAC at six weeks post-PN initiation and differences in growth between infants with IF receiving SMOFlipid versus the traditional Intralipid in our Canadian setting. Analysis is currently underway.

Funding Agencies

Women and Children’s Health Research Institute (WCHRI) at the University of Alberta
A142 ENDOSCOPIST EDUCATIONAL INTERVENTIONS ARE ASSOCIATED WITH IMPROVEMENTS IN ADENOMA DETECTION RATE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: González Moreno E , Bishay K , Calo N , Scaffidi M A , Grover S C , Forbes N
Published: February 2020

Background

Screening-related colonoscopy reduces the overall morbidity and mortality associated with colorectal cancer. In order for screening-related colonoscopy to be effective and safe, endoscopists must be well trained. However, a significant degree of variation exists between endoscopists in terms of adenoma detection rate (ADR) and cecal intubation rate (CIR). ADR in particular is an important colonoscopy quality metric that has been directly and inversely related to the rate of post colonoscopy colorectal cancer (PCCRC). Educational interventions aimed at endoscopists have been developed in an attempt to optimize the performance of colonoscopy. It is unknown what benefit these have on colonoscopy quality indicators or outcomes, if any.

Aims

We performed a systematic review and meta-analysis to determine whether there is an association between educational interventions aimed at endoscopists and improvements in colonoscopy quality indicators or outcomes.

Methods

An electronic search was conducted through August 2019 for studies reporting on targeted endoscopist educational interventions and associations with ADR or other colonoscopy quality indicators, or outcomes. Interventions such as hands-on training modules, skills enhancement courses were included Pooled rate ratios (RR) and weighted mean differences (WMD) were calculated using DerSimonian and Laird random effects models. A priori subgroup and sensitivity analyses were performed to assess for potential methodological or clinical factors associated with any of the outcomes of interest.

Results

From 2,253 initial studies, 14 were included in the systematic review, and 8 were included in the meta-analysis for ADR, representing 76,373 colonoscopies. Educational interventions were associated with improvements in ADR (RR 1.28, 95% confidence intervals, CI, 1.19–1.38). Educational interventions were also associated with improvements in overall polyp detection rate, PDR (RR 1.17, 95% confidence intervals, CI, 1.02–1.35). Educational interventions were not associated with longer withdrawal times (WMD -0.03 minutes, 95% CI, -0.57 - 0.51) or improved CIR (RR 1.00, 95% CI, 0.99 to 1.02), though unadjusted CIR was high in both the pre- and post-intervention groups, at 94.5% and 95.0%, respectively. Figure 1 shows Forest plots comparing pre-intervention and post-intervention rates for A) ADR, b) PDR and c) CIR.

Conclusions

Our study provides evidence that educational interventions aimed at endoscopists significantly improve ADR and overall PDR. Educational interventions did not impact withdrawal time or cecal intubation rates, and thus, the specific mechanisms for their benefit remain incompletely clear. As part of quality improvement programs to optimize colonoscopy performance, educational interventions should be considered.

Funding Agencies

None
A143 IMPACT OF A SIMULATION-BASED AUGMENTED REALITY CURRICULUM ON POLYPECTOMY SKILLS AMONG NOVICE ENDOSCOPISTS: A RANDOMIZED CONTROLLED TRIAL
Authors: Khan R , Scaffidi M A , Gimpaya N , Tham D , Atalla M , Al-Mazroui A , Gholami R , Satchwell J B , Walsh C M , Grover S C
Published: February 2020

Background

Polypectomy is an essential endoscopic skill. Training in polypectomy has been identified as a major deficiency for endoscopists worldwide as polypectomy occurs ad hoc during a colonoscopy when a polyp is detected, and a lack of standardized curricula. Augmented reality (AR), which superimposes computer-generated images on a user’s view of the world, can address these gaps by standardizing encounters with polyps while completing simulated procedures and enabling polypectomy-specific teaching.

Aims

Evaluate the impact of a simulation-based augmented reality curriculum on polypectomy performance among novice endoscopists.

Methods

This study includes two cohorts of participants from 2019 to 2020. In 2019, participants were randomized into either: (1) a control curriculum, involving 6 hours of simulation-based training (SBT) supplemented by expert feedback, interlaced with 4 hours of small group teaching on the theory of colonoscopy; or (2) the augmented reality curriculum (ARC), in involving the same curriculum with integrated AR, wherein participants engaged with an AR-enhanced video demonstrating relevant therapeutic and pathologic details during polypectomy. The SBT for all participants involved a progressive curriculum starting on a bench-top model and then moving to the EndoVR® virtual reality simulator. The primary outcome was polypectomy-specific performance using the Direct Observation of Polypectomy Skills (DOPyS) tool during a simulated polypectomy after training, with a maximum score of 100.

Results

Demographic characteristics are summarized in Table. In 2019, 21 novice endoscopists were enrolled. Immediately after training, the mean DOPyS score among ARC group participants was 76.2 (SD=17.9) compared to 71.8 (SD=13.2) among control group participants (Figure). In this interim analysis, there was no significant difference between groups. Data analysis will be completed after 2020 participants complete the study.

Conclusions

Interim results show a trend towards improved polypectomy performance with no significant difference. The results of this study have the potential to impact polypectomy education among novices. Simulation-based AR interventions may allow learners to progress towards achieving competency in polypectomy in a risk-free environment prior to first patient contact.

Funding Agencies

None
A146 MANAGEMENT OF ANTITHROMBOTIC THERAPY AFTER GASTROINTESTINAL BLEEDING: A MIXED METHODS STUDY OF HEALTHCARE PROVIDERS
Authors: Little D H , Pinto T , Douketis J , Dionne J , Holbrook A , Xenodemetropoulos T , Siegal D
Published: February 2020

Background

Oral anticoagulants (OAC) are permanently discontinued in up to 50% of patients after gastrointestinal (GI) bleeding despite ongoing thrombotic risk and evidence of benefit to restarting. The reasons for permanent discontinuation of OAC are unclear, but likely include concerns about re-bleeding and a lack of high-quality evidence. There are no studies evaluating healthcare provider values and preferences following OAC-related GI bleeding and their influence on decision-making about whether and when to resume OACs.

Aims

We aimed to (i) identify key factors (attributes) that influence healthcare provider decision-making regarding resumption of OAC after GI bleeding, (ii) determine the relative importance of these attributes, and (iii) to identify preference groups.

Methods

We conducted focus group discussions (FGD) with healthcare providers involved in the care of patients with OAC-related GI bleeding. Participants ranked the relative importance of the attributes identified during the FGD through a dot voting exercise. Transcripts were reviewed and themes (attributes) were identified. Results of the FGD informed a discrete choice experiments survey developed and analyzed using the Sawtooth software platform (Sawtooth Software, USA). The survey was pilot tested and modified by iterative feedback. A sample choice task is shown in Image 1. Hierarchical Bayes analysis was used to estimate preference coefficients (utilities) for each attribute. Latent class analysis was used to identify preference groups.

Results

There were 4 FGD involving 29 participants. The most important attributes identified and included in the survey were thrombosis risk, indication for OAC, index bleed severity, re-bleeding risk, and patient characteristics. There were 130 survey respondents practicing in hematology (n=68), internal medicine (n=30), gastroenterology (n=7), cardiology (n=4), family medicine (n=3), and others (n=18). The mean age was 45 years (±11) and 51% were male. Thrombosis risk and re-bleeding risk equally had the highest utility followed by index bleed severity, patient characteristics, and indication for OAC. Two preference groups were identified. The dominant preference group (78% of respondents) placed the highest utility on thrombosis risk and re-bleeding risk, while a minority (22% of respondents) placed the highest utility on index bleed severity.

Conclusions

Thrombosis risk and re-bleeding risk are equally the most important factors influencing OAC resumption following OAC-related GI bleeding. The severity of the index bleed is the most important factor in decision-making for a minority segment of healthcare providers. Further research on the dose, type and timing of OAC resumption is needed to determine the optimal balance between thrombosis and re-bleeding.

Funding Agencies

Heart and Stroke Foundation
A153 INCIDENCE OF DEEP VEIN THROMBOSIS (DVT) & PROPHYLAXIS PRACTICES IN DECOMPENSATED CIRRHOSIS INPATIENTS
Authors: Sarker A , Yelle D , Wooller K , Kelly E M
Published: February 2020

Background

The coagulation cascade is disturbed in cirrhosis. Patients are at risk for bleeding and coagulation through an imbalance of pro and anticoagulant factors.

Aims

We evaluated the incidence of DVTs and prevalence of DVT prophylaxis in hospitalized patients with decompensated cirrhosis.

Methods

A retrospective study of decompensated cirrhotic patients admitted to a tertiary care hospital. We evaluated the incidence of DVTs and use of DVT prophylaxis in this cohort. We also evaluated differences in patient characteristics in those who received DVT prophylaxis and between patients who did or did not develop DVTs.

Results

This study consisted of 520 cirrhotic patients, of which 258 patients (49.6%) received DVT prophylaxis. Of the remaining 262 patients who did not receive DVT prophylaxis, 199 (75.9%) had a documented contraindication to prophylaxis (bleeding, thrombocytopenia, both, or other). Compared to patients without DVT prophylaxis, patients who received prophylaxis were older (61.2 ± 11.2 vs 56.6 ± 10.9, p= 0.00001), had less varices (16.2% vs. 46%, p=0.0048), had more severe liver disease (MELD-Na 21 ± 6.5 vs 19.7 ± 7.3, p = 0.032), and fewer incidents of variceal (3.4% vs. 35.1%, p <0.001) and non-variceal (5.4% vs. 17.1%, p <0.001) gastrointestinal bleeding. DVT prophylaxed patients also had higher mean platelet values (149 ± 89 vs 112 ± 84, p <0.001), but similar baseline INRs (1.6 ± 0.4 vs 1.7 ± 0.8, p= 0.16), and were more likely to be admitted for non-bleeding complications of liver disease, including incidence of hepatic encephalopathy (37.9% vs 25.1%, p = 0.002) and spontaneous bacterial peritonitis (12.1% vs 6.5%, p=0.029). The incidence of radiographically identified DVT events in cirrhotic patients receiving DVT prophylaxis and those not receiving DVT prophylaxis was similar at 1.1 and 0.7%, respectively (OR 1.52, 95% CI 0.254 to 9.1, p = 0.65). There was no difference in liver disease severity between those with DVTs to those who did not develop DVTs, including similar MELD-Na, INR, platelets and hemoglobin values. Compared to patients without DVTs, those who developed DVTs had a higher bilirubin (95.8 ± 78.0 vs. 64.1 ± 24, p = 0.202) and INR (2.1 ± 0.7 vs. 1.6 ± 0.6, p = 0.07), as well as lower platelets (81.8 ± 23.3 vs. 131.4 ± 88.9). These groups had comparatively similar MELD-Na, albumin, creatinine, and hemoglobin levels.

Conclusions

DVT prevalence in this cohort of decompensated liver disease patients was overall low. DVT prophylaxis rates were moderate overall, however taking into account perceived contraindications such as thrombocytopenia or bleeding, patients appeared to be appropriately prophylaxed when indicated. Further study is required to identify which cirrhotic patients are at highest risk for DVTs and the safety of prophylaxis among patients with deranged lab values such as low platelets and elevated INR.

Funding Agencies

None
A178 DIAGNOSIS OF A MYCOTIC AORTIC ANEURYSM USING ENDOSCOPIC ULTRASOUND: A CASE REPORT
Authors: Reise-Filteau M , Toliopoulos P , Desilets E
Published: February 2020

Background

The role of endoscopic ultrasound (EUS) has expanded over the last decade. It is a well-established imaging modality in the diagnosis of gastrointestinal and pancreatic lesions as well as in mediastinal lesions. To date, EUS has not been reported in the literature for the diagnosis of mycotic aortic aneurysm after intravesical bacille Calmette-Guérin (BCG) therapy.

Aims

This case report describes the presentation and diagnosis of a mycotic aneurysm in the context of disseminated Mycobacterium bovis infection.

Methods

An 86-year-old man with previous intravesical BCG immunotherapy for the treatment of bladder carcinoma presented with weight loss and deconditioning at admission. Based on the patient’s past medical history and age, malignancy was suspected. An endoscopic ultrasound (EUS) revealed a mass at the lymph node station 9 masquerading as a lymphadenopathy. Multiple investigations were completed. Following the second EUS, the diagnosis of mycotic aneurysm was raised. The smear collected with EUS guided fine needle aspiration (FNA) was positive after Ziehl-Neelsen staining. The diagnosis of mycotic aneurysm to Mycobacterium bovis was confirmed.

Results

Treatment was initiated with rifampin, isoniazid and ethambutol. Despite optimal medical management, the patient presented with new onset fever, and a clinical deterioration with positive mycobacterial blood cultures. Within two months of admission, the treatment was discontinued and the patient died in palliative care.

Conclusions

Recognition of mycotic aneurysms is critical for institution of appropriate therapy and averting more severe complications, as they are associated with significant morbidity. This case aims to raise awareness to this rare disease after BCG treatment. It also highlights the novel role of EUSin the challenging diagnosis of mycotic aneurysm.

Funding Agencies

None
A191 EFFICIENCY OF TAILORED ERADICATION REGIMEN BASED ON ANTIBIOTIC SUSCEPTIBILITY AND CYP2C19 GENOTYPE TESTING IN CHILDREN WITH REFRACTORY HELICOBACTER PYLORI INFECTION
Authors: Ding Z , Pai N
Published: February 2020

Background

Refractory helicobacter pylori (Hp) is a challenging problem for pediatric population. Whether Hp culture and CYP2C19 genotype need to be done together still remains contraversial.

Aims

To explore the efficiency of tailored eradication therapy based on helicobacter pylori culture, susceptibility and CYP2C19 genotype in children who failed to empirical Hp eradication strategy in Baoding region(China).

Methods

This study is an observational cohort study. A total of 156 children with Hp infection who failed to amoxicillin + clarithromycin +omeprazole triple regimen in Baoding Children’s Hospital were selected as study subjects, and 92 of them underwent Hp culture and CYP2C19 genetic testing. 75 cases with successful Hp culture were defined as successful culture group and were treated according to antibiotics sensitivity and genotype results. 17 cases with failed culture were defined as culture failure group and were treated only based on the results of CYP2C19 genotype. 64 children who did not agree to perform Hp culture and CYP2C19 gene testing were defined as the empirical eradication therapy group and were treated with quadruple therapy (amoxicillin + metronidazole + omeprazole + bismuth). Antibiotics resistance, CYP2C19 gene polymorphism and therapeutic efficiency between the three groups were compared and analyzed.

Results

Results of Hp culture and antibiotics susceptibility: among the 75 children with successful culture, 72 (96%) were resistant to clarithromycin, 3 (4%) were resistant to metronidazole, 5 (7%) were resistant to levofloxacin, 5 (7%) were resistant to rifampicin, 1 (1%) was resistant to tetracycline, and there was no resistance to amoxicillin and furazolidone.

Results of CYP2C19 genotype test: among the 92 patients who underwent genotype test, 43 were Extensive Metabolizer (EM) (47%), 9 were Poor Metabolizer (PM) (10%), and 40 were Intermediate Metabolizer (IM) (44%).

Efficiency results: eradication rate in the successful culture group, culture failure group and empirical eradication therapy group was 99% (74/75),88%(15/17) and 72%(46/64), respectively. The eradication rate of children in the culture failure group and the empirical eradication therapy group were both lower than that in the successful culture group,and there were no difference between empirical eradication therapy group and culture failure group(p=0.283).

Conclusions

Tailored treatment based on Hp culture + antibiotics susceptibility and CYP2C19 genotype detection should be performed in children with refractory Hp infection. Hp culture + antibiotics susceptibility plays a more important role than CYP2C19 genotype.

Funding Agencies

None
A205 NON-POLAR HELMINTH-DERIVED METABOLITES MODULATES INNATE IMMUNE CELL RESPONSE AND PROTECTS MICE FROM EXPERIMENTAL COLITIS
Authors: Arai T , Siciliani E A , Jardim A , Lopes F
Published: February 2020

Background

The hygiene hypothesis postulates that the lack of exposure to helminth parasites would contribute to the development of the auto-inflammatory disease. There has been a significant increase in patients with inflammatory bowel disease (IBD) in North America. The previous study showed that infection with gastrointestinal helminth parasitedownregulated inflammatory pathways in several gut inflammation models. Given the known risks of live helminth infection, the therapy should direct towards helminth-derived properties.

Aims

To determine if helminth-derived metabolites treated mice are protected from DSS-induced colitis.

Methods

Preliminary, our screening reveled that non-polar fractions of 4 distinct helminth modulate LPS-induced inflammatory cytokines in vitro. 3% DSS or water was given to C57BL/6 mice for 5 days, followed by 4 days of a recovery period. The mice were treated intraperitoneal injection with non-polar helminth-derived metabolites (NPHM) on days 5, 6, and 7. Inflammation was assessed by disease activity,histopathology and cytokine mRNA expression in colons. The effect of NPHM on neutrophil chemotaxis was assess inin vitroand in vivo.

Results

The disease activity and histopathology score were significantly lower in DSS treated mice received NPHM. Also, NPHM treatment resulted in a decrease of an inflammatory cytokine such as TNF-α mRNA expression in the colon of mice with DSS-induced colitis. Mechanistically, NPHM reduced neutrophil chemotaxis.

Conclusions

NPHM treatment protects against DSS-induced colitis and modulate neutrophil response, which supports helminth therapy for IBD.

Funding Agencies

Supported by Hashimoto Municipal Hospital scholarship to TA and an NSERC Discovery grant to Fernando Lopes.
A211 ANTIFIBROTIC ACTIVITY OF NOVEL TYROSINE KINASE INHIBITORS IN VITRO
Authors: Kataria J , Lourenssen S , Blennerhassett M G
Published: February 2020

Background

Chronic inflammation in inflammatory bowel disease (IBD) causes structural alterations of the intestine. In Crohn’s disease, this can lead to stricture formation, arising from unclear interactions among local inflammatory cells, cytokines, and mesenchymal intestinal cells. Specifically, proliferation of smooth muscle and increased deposition of collagen-rich extracellular matrix leads to fibrosis and obstructive wall thickening. Since there are minimal treatment options, we explored the effects of two multimodal tyrosine kinase inhibitors, nintedanib and pirfenidone, which were recently approved for idiopathic pulmonary fibrosis (IPF), a chronic lung condition resembling Crohn’s disease.

Aims

To understand the basic pharmacology of two novel anti-fibrotic tyrosine kinase inhibitors and their effects on cell proliferation and collagen deposition.

Methods

In vitro model systems of adult rat colonic circular smooth muscle cells (CSMS), rat IEC-18 intestinal epithelial cells or mouse 3T3 were assessed for response to serum or the mesenchymal growth factor PDGF-BB, evaluating growth responses by proliferation assay, and type I collagen expression by immunocytochemistry and western blotting. Programmed cell death was detected by ICC and western blotting for caspase-dependent apoptotic markers.

Results

Both 3T3 fibroblasts and rat ISMC showed concentration-dependent proliferation in response to serum or PDGF application. Nintedanib reduced this response to baseline at EC100 of 2.3 ± 0.7 (n=5) µM, and EC50 of 0.3 ± 0.1 (n=6) µM without cytotoxicity, while pirfenidone was ineffective at levels ≤ 5mM. Nintedanib (10 µM) was ineffective against serum-induced growth of rat IEC-18 cells while blocking growth of rat CSMC or mouse 3T3 fibroblasts in parallel assays, suggesting a selective effect on mesenchymal cell types. In nintedanib-treated cultures, nuclear staining showed concentration-dependent reduction of mitotic figures with proportional appearance of nuclear fragmentation, typical of apoptosis. Western blotting for collagen I identified at 125kD band for both CSMC and 3T3 cells and suggested down-regulation with both nintedanib and pirfenidone.

Conclusions

Novel anti-fibrotic therapies for chronic idiopathic pulmonary disease display distinctive effects on ISMC proliferation and extracellular matrix production. These address molecular mechanisms of fibrosis that are in common with IBD, and so the translation of therapeutic approaches may be a promising treatment option. Detecting specific mechanisms of action of nintedanib, such as apoptosis, leads to better targets for therapeutic options.

Funding Agencies

NSERC