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Introduction With the expanding therapeutic armamentarium for inflammatory bowel disease (IBD), real-world data may help inform drug positioning. We assessed clinical, endoscopic, imaging, and biochemical response/remission outcomes in patients with Crohn’s disease (CD) treated with ustekinumab in a large Canadian IBD center. Methods A retrospective cohort study of CD patients was treated with ustekinumab. Clinical, endoscopic, radiological, and biochemical response and remission outcomes were stratified by prior biologic exposure status. Hazard ratios for biologic exposure status were estimated using Cox proportional hazard models and subgroup-specific incidence rates for healing. Results A total of 231 patients (55.9% female, median 45.8 years) were identified as receiving ustekinumab during the study period, with 2 patients subsequently excluded (N = 229). Of these patients, 79.0% (181 of 229) were bio-experienced, with 38.7% (70 of 181) having failed 1 biologic and 61.3% (111 of 181) having failed ≥2 biologics. At 3 months of follow-up after induction, clinical remission (Harvey-Bradshaw Index ≤4) was achieved by 59.1% (62 of 105) of bio-experienced patients and 79.4% (27 of 34) of bio-naïve patients (relative risk [RR], 1.34; 95% CI, 1.06-1.70; P = .013). Endoscopic remission (absence of mucosal ulcers) was achieved in 37.9% (33 of 87) cases. Rate of endoscopic healing (either endoscopic response or remission) per 1000 person-months was 72.7 (95% CI, 42.4-125.1) and 50.2 (37.9-66.4); and the median time to endoscopic response was 8.4 months (95% CI, 6.4-9.8) and 15.4 months (95% CI, 10.3-17.9) in bio-naïve vs bio-experienced patients, respectively. Imaging response/remission and steroid-free remission rates were higher in bio-naïve patients. Conclusion In this large real-world cohort of CD patients with complex phenotypes and high rates of prior biologic exposure, we observed that ustekinumab was effective and safe with higher rates of improvement in bio-naïve subjects across a range of end points.

Pulmonary extra-intestinal manifestations of inflammatory bowel disease are rare, comprising 0.21% to 0.4% of the inflammatory bowel disease population. Common symptoms include cough, chest pain, and dyspnea. Abnormal pulmonary function tests are common in these patients, with restrictive, obstructive, and diffusion capacity defects. CT scanning remains the most sensitive imaging technique to detect abnormalities. Pulmonary manifestations are diverse and include airway, parenchymal, and pleural disease. Large airway disease predominates, particularly bronchiectasis. Upper airway disease is rare but concerning for the development of acute airway compromise. To our knowledge, there are no reports of concurrent mediastinitis with tracheitis in the setting of inflammatory bowel disease. We present a case of a patient with ulcerative proctitis who experienced the development of inflammatory tracheitis and mediastinitis. Her disease responded to systemic steroids and biologic therapy. In addition to our case, we reviewed the literature and provide an approach to pulmonary complications as extra-intestinal manifestation of inflammatory bowel disease.

Trainees routinely participate in colonoscopy procedures, yet whether their involvement is positively or negatively associated with procedural quality is unknown because prior studies involved small number of trainees and/or supervisors, lacked generalizability, and/or failed to adjust for potential confounders.To assess the association between trainee participation and colonoscopy quality metrics.This multicenter population-based cohort study was conducted at 21 academic and community hospitals between April 1, 2017, and October 31, 2018, among consecutive adult patients undergoing colonoscopy. Procedures performed by endoscopists who did not supervise trainees were excluded. Statistical analysis was performed from April 3, 2017, to October 31, 2018.Participation by a trainee, defined as a resident or fellow enrolled in a gastroenterology or general surgery training program.The primary outcome was the adenoma detection rate (ADR), and secondary outcomes were sessile serrated polyp detection rate (ssPDR), polyp detection rate (PDR), cecal intubation rate (CIR), and perforation rate.A total of 35 499 colonoscopies (18 989 women [53.5%]; mean [SD] patient age, 60.0 [14.1] years) were performed by 71 physicians (mean [SD] time in practice, 14.0 [9.3] years); 5941 colonoscopies (16.7%) involved trainees. There were no significant differences in the ADR (26.4% vs 27.3%; P = .19), CIR (96.7% vs 97.2%; P = .07), and perforation rate (0.05% vs 0.06%; P = .82) when trainees participated vs when they did not participate, whereas the the ssPDR (4.4% vs 5.2%; P = .009) and PDR (39.2% vs 42.0%; P .001) were significantly lower when trainees participated vs when they did not. After adjustment for potential confounders, the ADR (risk ratio [RR], 0.97; 95% CI, 0.91-1.03; P = .30), PDR (RR, 0.98; 95% CI, 0.93-1.04; P = .47), and CIR (RR, 0.93; 95% CI, 0.78-1.10; P = .38) were not associated with trainee participation, although the ssPDR remained significantly lower (RR, 0.79; 95% CI, 0.64-0.98; P = .03).This study suggests that trainee involvement during colonoscopy was associated with reduced ssPDR but not other colonoscopy outcome measures. Extra care should be exercised when examining the right colon when trainees are involved.

Pulmonary extra-intestinal manifestations of inflammatory bowel disease are rare, comprising 0.21% to 0.4% of the inflammatory bowel disease population. Common symptoms include cough, chest pain, and dyspnea. Abnormal pulmonary function tests are common in these patients, with restrictive, obstructive, and diffusion capacity defects. CT scanning remains the most sensitive imaging technique to detect abnormalities. Pulmonary manifestations are diverse and include airway, parenchymal, and pleural disease. Large airway disease predominates, particularly bronchiectasis. Upper airway disease is rare but concerning for the development of acute airway compromise. To our knowledge, there are no reports of concurrent mediastinitis with tracheitis in the setting of inflammatory bowel disease. We present a case of a patient with ulcerative proctitis who experienced the development of inflammatory tracheitis and mediastinitis. Her disease responded to systemic steroids and biologic therapy. In addition to our case, we reviewed the literature and provide an approach to pulmonary complications as extra-intestinal manifestation of inflammatory bowel disease.

ObjectiveSeverity of coeliac disease depends in part on the extent of small intestinal mucosa injury. Patients with the most abnormal pathology have loss of duodenal villi CYP3A4, a drug-metabolising enzyme that inactivates many drugs. These patients are hypothesised to have greater systemic concentrations of felodipine, a drug which normally has low oral bioavailability secondary to intestinal CYP3A4-mediated metabolism. It serves as a representative for a class containing many medications.DesignA phase I, open-label, single-dose, pharmacokinetic study.SettingLondon, Ontario, Canada.ParticipantsPatients with coeliac disease (n=47) with positive serology and healthy individuals (n=68).Main outcome measuresPatients with coeliac disease—upper gastrointestinal endoscopy and oral felodipine pharmacokinetics study within a 3-week period. Healthy individuals—oral felodipine pharmacokinetics study with water and grapefruit juice.ResultsCoeliac stratification categories: Group A (n=15, normal), B+C (n=16, intraepithelial lymphocytosis with/without mild villous blunting) and D (n=16, moderate/severe villous blunting). Groups A, B+C and D had linear trends of increasing felodipine AUC0–8; mean±SEM, 14.4±2.1, 17.6±2.8, 25.7±5.0; p0–8(11.9±0.9 vs 26.9±0.9, p=0.0001) and Cmax (2.9±0.2 vs 7.7±0.2, p=0.0001) relative to those receiving grapefruit juice.ConclusionsIncreased felodipine concentrations in patients with coeliac disease were most probably secondary to decreased small intestinal CYP3A4 expression. Patients with severe coeliac disease and healthy individuals with grapefruit juice had equivalently enhanced effect. Thus, patients with severe coeliac disease would probably experience similarly altered drug response, including overdose toxicity, from many important medications known to be metabolised by CYP3A4. Patients with coeliac disease with severe disease should be considered for other clinical drug management, particularly when there is the potential for serious drug toxicity.

Background Aminosalicylates are the most frequently prescribed drugs for patients with Crohn’s disease (CD), yet evidence to support their efficacy as induction or maintenance therapy is controversial. Aims To quantify aminosalicylate use in CD clinical trials, identify factors associated with use, and estimate direct annual treatment costs of therapy. Methods MEDLINE, Embase, and CENTRAL were searched to April 2017 for placebo-controlled trials in adults with CD treated with corticosteroids, immunosuppressants, or biologics. The proportion of patients co-prescribed aminosalicylates in placebo arms was pooled using a random effects model. Meta-regression was used to identify factors associated with aminosalicylate use. Annual treatment costs were estimated using the 2016 Ontario Drug Benefit Program. Results Forty-two induction and ten maintenance trials were included. The pooled proportion of patients co-prescribed aminosalicylates was 44% [95% CI: 39%-49%] in induction trials and 49% [95% CI: 35%-64%] in maintenance trials. There was substantial to considerable heterogeneity (I2=86.0%, 91.8% for induction and maintenance trials, respectively). In multivariable meta-regression, aminosalicylate use has decreased over time in induction trials (OR 0.50 [95% CI: 0.34, 0.74] per 10-year increment). Whilst a decline has been seen over time, 35% of CD patients were still using aminosalicylates in contemporary trials from the last five years. The estimated annual cost for the lowest price mesalamine formulation is approximately $32 million for the Canadian CD population. Conclusions Over one-third of CD patients entering clinical trials are still co-prescribed aminosalicylates. A definitive trial is needed to inform the conventional practice of using aminosalicylates as CD maintenance therapy.

Background Performing a minimum number of colonoscopies annually has been proposed by some jurisdictions as a requirement for maintaining privileges. However, this practice is supported by limited evidence. Aims The objective of this study was to determine if annual colonoscopy volume was associated with colonoscopy quality metrics. Methods A population-based study was performed using the Southwest Ontario Colonoscopy cohort, which consists of all adult patients who underwent colonoscopy between April 2017 and Oct 2018 at 21 academic and community hospitals within the health region. Data were collected through a mandatory quality assurance form completed after each procedure and pathology reports were manually reviewed. Physician annualized colonoscopy volumes were compared by correlation analysis to each quality-related outcome, by means of the area under the receiver operating characteristics curve (AUROC), and logistic regression. The prognostic value of colonoscopy volume was also adjusted for case-mix and potential confounders in separate regression analyses for each outcome. The primary outcome was ADR. Secondary outcomes were polyp detection rate (PDR), sessile serrated polyp detection rate (SSPDR), and cecal intubation. Results A total of 47,195 colonoscopies were performed by 75 physicians (37.5% by gastroenterologists, 60% by general surgeons, 2.5% others). There were no clear relationships between annual colonoscopy volumes and study outcomes. Colonoscopy volume was not associated with ADR (OR 1.03, 95% CI 0.96–1.10, p=0.48) and corresponded to an AUROC not significantly different from the null (AUROC 0.52, 95% CI 0.43–0.61, p=0.65). Multi-variable regression adjusting for case-mix also demonstrated no predictive value of annual colonoscopy volume for the primary outcome (OR 1.03, 95% CI 0.94–1.12, p=0.55). Similarly, analyses of secondary outcomes failed to find an association between colonoscopy volume and PDR, SSPDR, or cecal intubation (Table 1). Conclusions Annual colonoscopy volumes do not predict ADR, PDR, SSPDR, or cecal intubation rate. Results of unconditional and conditional approaches for examining the predictive value of annual colonoscopy volume for quality related outcomes. Funding Agencies None

Background and study aim In percutaneous endoscopic gastrostomy (PEG) with jejunal extension (PEGJ) procedures, retrograde migration of the jejunal extension tube into the stomach during endoscope withdrawal is a frustrating problem. We describe the novel “wedge” technique for inserting the jejunal extension tube, utilizing single-balloon enteroscopy to anchor it in place. Patients and methods Prospective 1-year study of consecutive patients undergoing PEGJ insertion at a single tertiary care center. The primary outcome was number of pyloric intubations required to place the jejunal extension tube. Secondary outcomes included success rate, time, and complications related to jejunal extension tube insertion. Results 17 patients underwent the procedure. The jejunal extension tube was inserted at the first attempt in 15 patients (88.2 %) and 2 required another pyloric intubation. Abdominal X-ray showed that all PEGJ tubes were successfully seated in the proximal jejunum. The mean (SD) time required for jejunal extension insertion was 16.9 (8.6) minutes. Two adverse events occurred due to PEG insertion although none were related to the jejunal extension insertion itself. Conclusions: The “wedge” technique is an effective and easy method for inserting a jejunal extension tube after PEG insertion.

Fecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. It has proven to be an effective tool in initial screening as well monitoring response to therapy. The aim of this study is to examine the utility of fecal calprotectin both as a predictor for the escalation of therapy in established inflammatory bowel disease and as a predictor of de novo diagnosis.Patients with signs and symptoms concerning for inflammatory bowel disease presenting to outpatient clinics were recruited to provide fecal calprotectin stool samples prior to endoscopic evaluation. Patients were followed up for at least one year and monitored clinically for any change in symptomatology, escalation of therapy or development of IBD, confirmed endoscopically.A total of 126 patients, of whom 72 were known to have underlying inflammatory bowel disease, were included in the final analysis. Among the patients with elevated fecal calprotectin levels and known inflammatory bowel disease, 66% (33/50) went on to have escalation of therapy within 12 months compared to 18% (4/22) if the fecal calprotectin levels were in the normal range (p .0001). For the remaining patients who at baseline did not have inflammatory bowel disease and a normal endoscopic evaluation, elevated fecal calprotectin resulted in no cases (0/17) of a new diagnosis in the next 12 months.Fecal calprotectin is a useful test for predicting escalation of therapy in established inflammatory bowel disease.

Background The interleukin-6 family cytokine, oncostatin-M (OSM) has been associated with a lack of remission to tumor necrosis factor-α antagonists (anti-TNFs) in small cohorts of patients with inflammatory bowel disease (IBD). We aimed to further evaluate the association between plasma OSM concentrations and response to anti-TNFs (infliximab and adalimumab) in addition to other clinical outcomes in both ulcerative colitis (UC) and Crohn’s disease (CD). Methods A retrospective cohort study was carried out in patients with IBD with a history of anti-TNF exposure. Blood samples, collected prior to anti-TNF exposure, were analyzed by enzyme-linked immunosorbent assay for the presence and quantity of OSM. The primary outcome evaluated was clinical remission at 1-year based on the Harvey Bradshaw Index (HBI, remission, HBI Results One hundred and fourteen patients with IBD (CD, n=73; UC, n=40) seen at a tertiary care centre in London, Ontario Canada, were included in the analyses. Patients received one of infliximab (n=61) or adalimumab (n=53). For those with UC achieving clinical remission at 1-year (n=24), the mean OSM concentration was 84.5±119.7pg/ml versus those not achieving clinical remission (n=16) where the mean OSM concentration was 1064.0±958.8pg/ml (p A threshold OSM concentration of 168.7pg/ml in CD and 233.6pg/ml in UC separated those who achieved clinical remission at 1-year on an anti-TNF from those who did not (CD: area under the receiver operator characteristic curve, AUROC=0.880, 95%CI=0.79-0.96, p In CD, participants with a plasma OSM concentration above the threshold concentration of 168.7pg/ml, were more likely to discontinue their anti-TNF at 1-year (p Conclusion OSM plasma concentrations were associated with response to anti-TNFs at 1-year in IBD. A threshold OSM concentration of 168.7pg/ml distinguished patients with CD at-risk of poor clinical outcomes.

Background Azathioprine (AZA)-induced pancreatitis is an unpredictable and dose-independent adverse event affecting 2%-7% of patients with inflammatory bowel disease (IBD) patients treated with AZA. There are no tools in clinical practice to identify at-risk individuals; however, a genome wide association study (GWAS) identified a strong association between the Class II HLA gene region polymorphism (rs2647087) and thiopurine-induced pancreatitis. Aim To independently confirm the findings of the GWAS in an IBD cohort, to evaluate its utility in clinical practice and to offer a novel AZA treatment algorithm for IBD based on pharmacogenomic principles. Methods A retrospective cohort study evaluated 373 AZA-exposed IBD patients from a tertiary care academic centre in London, Canada. Due to the limited number of patients taking mercaptopurine (MP), such patients were not included this cohort. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype and were sub-divided based on the presence (n = 13) or absence (n = 360) of an AZA-induced pancreatitis diagnosis. The risk of AZA-induced pancreatitis was assessed based on rs2647087 genotype. Results The risk of pancreatitis during AZA-therapy was highly predictable and genotype dependent: 0.53% for wild type (A/A), 4.25% (OR = 4.19, 95% CI 1.02-36.45, P = 0.044) for heterozygous (A/C), and 14.63% (OR = 15.83, 95% CI 3.80-145.26, P = 0.0001) for homozygous variant (C/C) patients. Conclusions The class II HLA region (at rs2647087) is an important marker of AZA-induced pancreatitis risk. We propose a simple and clinically implementable algorithm based on rs2647087 and TPMT genotypes for AZA selection and dosing for patients with IBD.

BACKGROUND: Stricture formation is one of the most common complications of Crohn’s disease. Management options include medical therapy and surgical resection or strictureplasty. An increasingly more common middle ground approach is colonoscopic balloon dilation (BD). AIMS: The aim of this study was to examine the efficacy and complication rate of BD in a population of patients with symptomatic strictures. METHODS: Retrospectively, all patients in our local IBD practice who underwent colonoscopic balloon dilation with a diagnosis of a symptomatic Crohn’s stricture between January 2006 and March 2016 were reviewed. Demographic data were collected and technical and clinical success determined to compare the results between primary and anastomotic strictures. Technical success was defined as subjective improvement in the stricture and the ability to pass the scope through it. Clinical success was defined as subjective clinical improvement at follow up 3 months or more after the procedure. Pearson’s chi-squared test was used to compare relative efficacy. RESULTS: 98 patients were identified with a total of 108 strictures dilated. The mean age of the patients was 45.2 years (range 20–79). 64.3% of the patients were females. 51.9% of the strictures were anastomotic. 32.4% were on immunomodulators (methotrexate, azathioprine or 6-mercaptopurine) and 25.9% on anti-TNF therapy at the time of the dilation. 30.6% were on steroids. An adult Olympus colonoscope (diameter 13.2 mm) was used in 86.1% of cases. 31.5% of strictures were estimated to be less than 10 mm in diameter. 82.4% of the strictures were impassable prior to dilation. The most common balloon diameter was 15 mm (24.1%) with a median dilation diameter of 16.5 mm. Technical success was achieved in 62%. Clinical success was achieved in 84.3%. Complications were observed in one patient (post colonoscopy bleeding requiring hospitalization for supportive measures and blood transfusion). Comparison of primary and anastomotic strictures demonstrated a statistically significant difference in technical success (73.1% vs 51.8%, p=0.023) but not clinical success (86.5% vs 82.1% p=0.531). CONCLUSIONS: Colonoscopic balloon dilation of both primary and anastomotic strictures is feasible and appears to be clinically efficacious in a majority of patients with symptomatic primary and anastomotic Crohn’s strictures. Complication rates, though not insignificant, appear to be acceptably low. FUNDING AGENCIES: None

BACKGROUND: Inadequate visualization during upper gastrointestinal bleeding (UGIB) is a common problem. The BioVac direct suction device is designed to enhance endoscopic suction to improve visualization. We initiated a randomized clinical trial to determine the efficacy of this device (NCT02150941). AIMS: In this report, we present the results of a feasibility analysis. METHODS: Between July 2014 and June 2016, patients admitted to two academic hospitals undergoing endoscopy for UGIB with suspicion of active bleeding (ie. fresh blood hematemesis, hemodynamic instability, acute drop in hemoglobin) were invited to participate. EGD was performed and patients where the source of bleeding was not found due to poor visualization after 5 minutes were randomized to BioVac or standard endoscopy suction. Due to the difference in suctioning power, a placebo was not possible. Instead, the procedure was recorded and assessed by a blinded outcome assessor. The procedure was otherwise performed at the discretion of the endoscopist without input from the study staff. The primary outcome was whether the bleeding source was found. Secondary outcomes included the mucosa visualization score, endoscopic therapy, need for repeat endoscopy within 7 days, rebleeding, and 30-day mortality. RESULTS: Over 24 months, a total of 70 subjects were recruited. 60 subjects were excluded due to the source of bleeding being found within the first 5 minutes or there being no blood in the upper GI tract. Of the 10 subjects randomized, 7 were assigned to standard endoscopy suction and 3 to BioVac. The mean (SD) age was 68.3 (13.4) and 30% were females. 60% presented with fresh blood hematemesis, 30% had a history of cirrhosis, 50% bled as an inpatient, and 60% had an ASA score of ≥4. The source of bleeding was found in 66% in the BioVac group and 71% among the controls. The mean (SD) mucosal visualization score was 15.3 (2.6) for BioVac and 7.7 (3.3) for controls although there was no difference in the application of endoscopy therapy (33% in both groups). 33% in the BioVac group and 83% in the control group required a repeat endoscopy within 7 days. No patients rebleed or died in the BioVac group compared to 3 who rebleed and 4 who died in the control. CONCLUSIONS: Study feasibility is hampered by low recruitment and high exclusion rates. A multi-centre approach to increase recruitment and the development of a better clinical prediction tool for active bleeding are required. FUNDING AGENCIES: Vantage Endoscopy

BACKGROUND: Patients with moderate to severe Crohn’s disease refractory or intolerant to steroids, immunomodulators and anti-TNF therapy currently have few options for medical management outside of clinical trials. Ustekinumab, a monoclonal antibody, which inhibits interleukins 12 and 23 is currently being used safely and effectively to treat patients with psoriasis and recent studies suggest that it may be of value in treating moderate to severe Crohn’s disease in patients both naive and refractory to anti-TNF therapy. Currently the intravenous formulation of ustekinumab used in these studies is unavailable for use outside of clinical trials. AIMS: The aim of this study was to examine the clinical efficacy of subcutaneously (sc) loaded ustekinumab in patients with moderate to severe Crohn’s disease who had failed at least one anti-TNF agent. METHODS: All patients given a loading dose of ustekinumab 270 mg sc over two weeks were included in this retrospective analysis. Baseline demographic data was collected. The primary outcome was the proportion of patients who achieved a Harvey-Bradshaw Index (HBI)

BACKGROUND: Azathioprine (AZA)-induced pancreatitis is an unpredictable and dose-independent adverse event affecting 2–7% of patients with inflammatory bowel disease (IBD) patients treated with AZA. There are no tools in clinical practice to identify at-risk individuals; however, a genome wide association study (GWAS) identified a strong association between the Class II HLA gene region polymorphism (rs2647087) and AZA-induced pancreatitis. AIMS: To independently confirm the findings of the GWAS in an IBD cohort, to evaluate its utility in clinical practice and to offer a novel AZA treatment algorithm for IBD based on pharmacogenomic principles. METHODS: A retrospective cohort study evaluated 373 AZA-exposed IBD patients from a tertiary care academic centre in London, Canada. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype and were sub-divided based on the presence (n = 13) or absence (n = 360) of an AZA-induced pancreatitis diagnosis. The risk of AZA-induced pancreatitis was assessed based on rs2647087 genotype. RESULTS: The risk of pancreatitis during AZA-therapy was highly predictable and genotype dependent: 0.53% for wild-type (A/A), 4.25% (OR=4.19, 95%CI 1.02–36.45, p=0.044) for heterozygous (A/C), and 14.63% (OR=15.83, 95%CI 3.80–145.26, p=0.0001) for homozygous variant (C/C) patients. CONCLUSIONS: The class II HLA region (at rs2647087) is an important marker of AZA-induced pancreatitis risk. We propose a simple and clinically implementable algorithm based on rs2647087 and TPMT genotypes for AZA selection and dosing for patients with IBD. FUNDING AGENCIES: CAG, CCC, CIHRCancer Care Ontario

BACKGROUND: Stricture formation is a common and challenging complication of Crohn’s disease (CD) with a significant impact on disease management. Treatment options include medical therapy, surgical resection or strictureplasty. Another less invasive approach is colonoscopic balloon dilation (CBD). AIMS: To assess the efficacy and safety of CBD in our cohort of Crohn’s disease patients with strictures. METHODS: From January 2006 to March 2016, we conducted a retrospective chart review of CD patients in our practice who underwent CBD. The primary outcomes were technical and clinical success of CBD. Technical success was defined as subjective improvement in the stricture and the ability to pass the scope through it post-dilation. Clinical success was defined as subjective clinical improvement at follow up visits. Secondary outcomes included post-CBD complication rate, surgery-free survival and repeat CBD-free survival. RESULTS: A total of 123 patients with 152 strictures were included in the analysis. The mean age of the sample patients was 48.5 years (range 20–86). 63.2% of patients were females. Anastomotic strictures were the cause in (52.6%). Medications used at the time of CBD include biologic therapy in 30.3%, immunomodulators (azathioprine, methotrexate and 6-mercaptopurine) in 30,9%, steroids in 27.6% and 5-ASA derivatives in 7.2%. The median dilation diameter was 15 mm. 73% of the procedures had technical success while 88.8% had clinical success. CBD of primary strictures was more likely to achieve technical success (80.6% vs. 66.3%; p=0.047) but not clinical success (90.3% vs. 87.5%; p=0.59). Two patients experienced post-CBD bleeding (requiring hospitalization and blood transfusion) while another two patients experienced self-limited pain. Dilated secondary strictures were more likely to undergo a repeat-CBD (38.8% vs. 31.9%; p=0.38) and post-CBD surgery (28.8% vs. 25%; p=0.6) when compared to primary strictures. CONCLUSIONS: Overall, CBD is an effective treatment option for CD strictures with more success in primary strictures. Serious complications were encountered, although not insignificant, at a low rate. FUNDING AGENCIES: None

BACKGROUND: EoE is an increasingly recognized cause of upper gastrointestinal symptomatology particularly dysphagia. The gold standard for diagnosis is the presence of increased eosinophils on esophageal biopsies. To distinguish EoE from esophageal eosinophilia due to gastroesophageal reflux disease (GERD), many physicians routinely separate biopsies from the mid and distal esophagus, theorizing that eosinophils will be more numerous in the distal esophagus in GERD and more diffusely distributed in EoE. The aim of our study was to determine if this approach was truly helpful in clinical practice. AIMS: To determine the utility of comparing distal and mid-esophageal counts in differentiating EoE from GERD. METHODS: All endoscopically obtained biopsies of the esophagus taken at London Health Sciences Centre between July 1, 2011 and June 30, 2014 were eligible for review. Patients were only included if they were 18 year old or older and biopsies were taken from the mid and distal esophagus for non-neoplastic findings and separated for review. The pathology was then reviewed by a pathologist blinded to diagnosis and a mean eosinophil count per high-power field (hpf) was calculated for each area. A delta eosinophil count (DEC) was calculated by subtracting the mean count in the distal esophagus from the mean count in the mid-esophagus. If multiple endoscopies were performed, only the first biopsy after the study initiation date was used. RESULTS: 603 patients were included in the analysis. Of these 138 (22.9 %) had a final diagnosis of GERD, 124 (20.6 %) EoE and 341 (56.5 %) normal. The most common predominant symptoms in GERD were heartburn 99 (71.7 %) and dysphagia to solids 70 (50.7 %). The most common predominant symptoms in EoE were dysphagia to solids 90 (72.6 %), atopic symptoms 41 (33.1 %), heartburn 40 (32.3 %) and food impaction 38 (30.6 %). The most common endoscopic findings in EoE were furrows 81 (65.3 %), trachealization 70 (56.4 %) and stricture 29 (32.4 %). The mean eosinophil count in the distal and mid-esophagus respectively was 6.6 and 2.8 in GERD, 80.4 and 76.9 in EoE and 0 and 0 in normal patients. The DEC was positive in 20.3 % of GERD patients and 41.1 % of EoE patients. The mean DEC was -3.8 in GERD patients and -3.5 in patients with EoE. CONCLUSIONS: Mucosal eosinophilia is significantly more pronounced in patients with EoE although the difference between eosinophil counts in the mid and distal appears to be of only marginal value in distinguishing between the two diagnoses. Separating specimens for analysis does not appear to be necessary. FUNDING AGENCIES: None

BACKGROUND: Despite anti-rejection immunosuppressive therapies post-liver transplantation (LT), patients with concurrent inflammatory bowel disease (IBD) may have persistent bowel inflammation that requires addition of biologic therapy. AIMS: To evaluate the safety of combination biologic and anti-rejection therapy in IBD patients after LT. METHODS: The LT Registry at London Health Sciences Centre (LHSC) was searched to identify all patients undergoing LT from 1985–2018. IBD patients initiated on biologic treatment post-LT, in addition to anti-rejection therapy, were eligible for inclusion. Medical chart review was conducted to extract safety outcomes, including rates of infections, malignancy, colectomy and death. RESULTS: 19 patients were included (78.9% male, mean age 46.0 years, 8 patients with ulcerative colitis), followed for a median duration of 19 months (IQR 5.8, 30.8). Indications for LT included: primary sclerosing cholangitis (PSC) (14/19, 73.7%), autoimmune hepatitis (AIH) (2/19, 10.5%), AIH-PSC overlap syndrome (2/19, 10.5%), and biliary atresia (1/19, 5.3%). Post-LT, six patients were treated with only TNF antagonists (infliximab in 5 patients, golimumab in 1 patient); eight patients with only anti-integrin therapies (vedolizumab in 7 patients, natalizumab in 1 patient); and five patients with sequential TNF antagonists followed by either ustekinumab (n=2) or vedolizumab (n=3). Six patients required long-term prednisone. The most commonly used anti-rejection therapies were tacrolimus and mycophenolate mofetil. Disease course was complicated by infections in nine patients (47.4%), most commonly Clostridium difficile colitis (4/19, 31.6%). One patient had recurrent C. difficile infection and one patient had CMV colitis and viremia. Other infections included cholangitis (n=2), perianal abscess (n=1), JC virus seroconversion but without progressive multifocal leukoencephalopathy (n=1) and hospital-acquired pneumonia (n=1). Two patients required colectomy for refractory colitis. One patient required re-transplantation due to PSC recurrence. No deaths or malignancies were reported although one patient developed low grade colonic dysplasia. CONCLUSIONS: This is the largest reported case series from a single center to date evaluating the safety of combination biologic therapy with anti-rejection regimens in IBD patients post-LT. Whilst there appeared to be an increased risk of enteric infections, especially Clostridium difficile,there were no life-threatening infections reported. Active screening for enteric infections should be pursued in these patients presenting with increased IBD symptoms. FUNDING AGENCIES: None

Melena is a symptom of upper gastrointestinal bleeding and usually indicates bleeding proximal to the ligament of Treitz. However, whether melena predicts bleeding in the proximal small intestine in patients with obscure gastrointestinal bleeding (OGIB) is unknown and the objective of this study. A retrospective cohort study of consecutive patients undergoing capsule endoscopy for OGIB between July 2009 and May 2016 was conducted. Subjects were categorized based on the presence of melena, and the primary outcome was identification of a bleeding source within the proximal 2/3 of the small intestine. Multi-variable regression was performed to control for confounders. During the study, 288 patients met the eligibility criteria. Subjects with melena accounted for 37.1% of the cohort and were more likely to be older (mean age 66.9 vs. 63.9, p = 0.0457), take warfarin (15.1 vs. 9.4%, p = 0.0122), and have a lower 12-month hemoglobin nadir (7.3 vs. 8.3 g/dL, p = 0.0002). On crude analysis, 56.1% of patients with melena had a bleeding source within the proximal small intestine compared to 34.8% for those without (RR 1.61, 95% CI 1.24–2.09, p = 0.0004). On multi-variable analysis, the presence of melena doubled the odds of finding a bleeding site within the proximal small intestine (OR 1.97, 95% CI 1.17–3.33, p = 0.010). The presence of melena doubles the odds of finding a bleeding site within the proximal small intestine among patients with OGIB, and deep enteroscopy, if performed before a capsule study, should begin with an antegrade approach in these patients.

Background Genetic variation in the HLADQA1-HLADRB1*07:01 haplotype is strongly associated with azathioprine (AZA)-induced pancreatitis in inflammatory bowel disease (IBD). We aimed to evaluate the utility of pre-emptive HLA DQA1-HLADRB1*07:01 screening to reduce the risk of AZA-induced pancreatitis in an IBD population. Methods A prospective cohort study is ongoing in IBD patients being considered for AZA therapy who are assigned to pre-treatment HLA DQA1-HLADRB1*07:01 (rs2647087) screening (n = 372 currently recruited) and compared with historical controls who have received AZA standard of care (n = 373). Participants in the pre-emptively screened group found to be variant carriers (AC or CC) are excluded from AZA treatment while wild type carriers (AA) received standard dosing. The incidence of clinically diagnosed pancreatitis (lipase >3 times the upper limit of normal and one of abdominal pain or imaging findings suggestive of pancreatitis) occurring within 3 months in all participants with AZA exposure is being compared between the prospective and historic populations. Results The minor allele frequency of HLADQA1-HLADRB1*07:01 is 29%. To date, 194 participants (AA genotype) in the pre-emptively-screened cohort have received AZA therapy and completed the 3-month follow-up period. An additional 136 individuals with AA genotype are needed to obtain the target sample size (n = 330). Thus far, fewer cases of AZA-induced pancreatitis are seen in the pre-emptively screened population (pre-emptive cohort, 1/194 vs. historical controls, 13/373; odds ratio = 7.01, 95%CI = 0.91–53.98, p = 0.04). Conclusion Pre-emptive HLA DQA1-HLADRB1*07:01 screening may reduce the risk of pancreatitis during AZA treatment in patients with IBD. Completion of this study will help define whether HLA DQA1-HLADRB1*07:01 screening is a clinically-actionable and relevant tool for the safe use of AZA therapy in IBD.

BACKGROUND: Melena is a hallmark symptom of upper gastrointestinal bleeding and results from the digestion of blood lost proximal to the ligament of Treitz in the majority of cases. However, whether melena also predicts bleeding in the proximal small intestine (SI) in the setting of obscure gastrointestinal bleeding (OGIB) is unknown. AIMS: The objective of this study was to determine the predictive value of melena for determining the location of SI bleeding in OGIB. METHODS: A retrospective cohort study was conducted of all patients who underwent capsule endoscopy (CE) for OGIB at London Health Sciences Centre between 2009 and March 2016. The presenting symptoms were recorded and categorized as melena or non-melena (ie. hematochezia and occult OGIB with iron deficiency anemia (IDA)). The primary outcome was diagnosis of a bleeding site between 0 - 50% SI transit time. Baseline demographics, comorbidities, medication usage, hemoglobin, and blood transfusion requirements were noted. The association between melena and proximal SI bleeding was determined using chi-square. RESULTS: 312 patients underwent CE for OGIB during the study period. Mean (SD) age was 63.9 years (15.4), and 55% were female. 36% of patients had melena, 14% had hematochezia, and 48% had only IDA. Blood transfusion was required within the past 12 months in 70% of patients and 14% of cases were performed as inpatients. The mean (SD) follow-up time was 16 months (24.1). The overall diagnostic rate was 45%, with angioectasias being the most common etiology (27%). 46% of patients with melena had a bleeding site within the proximal half of the SI compared to 31.3% who did not have melena (RR 1.47, p=0.01). The mean (SD) SI transit time for bleeding site was 21.2% (25.8) for those with melena and 34.7% (33.4) for those without (p=0.008). CONCLUSIONS: The probability of locating a bleeding site within the proximal half of the SI is 47% greater among OGIB patients with melena than those without. As such, antegrade double balloon enteroscopy without preceding CE may be warranted in this population. FUNDING AGENCIES: Schulich Research Opportunities Program

Objectives Transcutaneous bowel sonography is a nonionizing imaging modality used in inflammatory bowel disease. Although available in Europe, its uptake in North America has been limited. Since the accuracy of bowel sonography is highly operator dependent, low-volume centers in North America may not achieve the same diagnostic accuracy reported in the European literature. Our objective was to determine the diagnostic accuracy of bowel sonography in a nonexpert low-volume center. Methods All cases of bowel sonography at a single tertiary care center during an 18-month period were reviewed. Bowel sonography was compared with reference standards, including small-bowel follow-through, computed tomography, magnetic resonance imaging, colonoscopy, and surgical findings. Results A total of 103 cases were included for analysis during the study period. The final diagnoses included Crohn disease (72), ulcerative colitis (8), hemolytic uremic syndrome (1), and normal (22). The sensitivity and specificity of bowel sonography for intestinal wall inflammation were 87.8% and 92.6%, respectively. In the subset of patients who had complications of Crohn disease, the sensitivity and specificity were 50% and 100% for fistulas and 14% and 100% for strictures. One patient had an abscess, which was detected by bowel sonography. Abnormal bowel sonographic findings contributed to the escalation of treatment in 55% of cases. Conclusions Bowel sonography for inflammatory bowel disease can be performed in low-volume centers and provides diagnostic accuracy for luminal disease comparable with published data, although it is less sensitive for complications of Crohn disease.

Background In many clinical situations, stool examinations for ova and parasites (O&P) are routine in the work-up of patients with acute or chronic diarrhea. Frequently, these tests are found to be negative for pathogens. The purpose of this study was to examine the diagnostic yield of routine stool testing for O&P in a Canadian tertiary care centre and to estimate the potential clinical benefit of a positive result. Patients and Methods All stool samples sent to the central microbiology laboratory at London Health Sciences Centre were reviewed over a 5-year period ending January 2010. Initial screening was done by direct antigen testing using an enzyme immunoassay (EIA) technique followed by direct microscopy for negative results where there was a high index of suspicion and for positive results to rule out any concurrent parasites not included in the EIA kit. Pathogens identified were categorized and their potential susceptibility to metronidazole was estimated. No clinical data were available, as this was purely a utilization study. Results A total of 5812 stool tests were ordered. Of these, 5681 (97.7%) were completed. The most common reasons for an incomplete test were sample leakage (n = 38) and use of the incorrect collection kit (n = 32). Direct microscopy identified white blood cells in 17% of patients with positive testing. The most common pathogen was Giardia lamblia , which was detected in 45/83 (54%) of positive specimens. Entamoeba histolytica / Entamoeba dispar was identified in 16/83 (19%) and Cryptosporidium spp. in 10/83 (12%) of positive specimens. Microorganisms not thought to be pathogenic were identified in 7/83 (8%). Direct laboratory costs independent of labor were estimated at $1836 per clinically significant organism identified. Of the 77 specimens positive for pathogenic organisms, 62 (81%) were likely to be sensitive to treatment with metronidazole. Conclusion In a tertiary care centre, the diagnostic yield of routine testing of stool for O&P during the evaluation of patients with acute or chronic diarrhea is low. Most clinically significant positive results should be responsive to metronidazole, but empirical treatment is not encouraged. Strategies to identify patients with a higher likelihood of harboring pathogenic parasites and consideration of empiric metronidazole therapy for patients at highest risk merit further research.

Background and Aims The major transporter responsible for bile acid uptake from the intestinal lumen is the apical sodium-dependent bile acid transporter (ASBT, SLC10A2). Analysis of the SLC10A2 gene has identified a variety of sequence variants including coding region single nucleotide polymorphisms (SNPs) that may influence bile acid homeostasis/intestinal function. In this study, we systematically characterized the effect of coding SNPs on SLC10A2 protein expression and bile acid transport activity.

Pure oats are safe for most patients with celiac disease, but concerns regarding contamination by other grains limit their consumption. The Canadian Celiac Association recently released guidelines governing the production of pure oats. The objective was to test the safety of a product manufactured under these guidelines.Fifteen adults with established, biopsy-confirmed celiac disease of ≥ 1 year duration were challenged with 350 g/wk of pure oats for 12 weeks. Symptom scores, weight, hemoglobin, ferritin, albumin, and tissue transglutaminase (tTG) were assessed at weeks 0, 6, and 12. Duodenal biopsies were obtained before and after oat challenge and assessed based on the modified Marsh-Oberhuber score. Compliance with a gluten-free diet was monitored with random food diaries.Fifteen patients completed the study and were analyzed in intention-to-treat and per-protocol analyses. There were no significant changes in symptom scores, weight, hemoglobin, ferritin, or albumin during oat consumption. The tTG remained negative in all patients, and the histology scores did not significantly change during oat challenge. The only relapse occurred in a patient who became noncompliant with her gluten-free diet.The findings support the safety of pure, uncontaminated oats manufactured under Canadian Celiac Association guidelines for patients with celiac disease.

M. Alkhattabi, V. Jairath, N. Chande, P. Walton-Mennill, J.C. Gregor Western University, London, ON, Canada BACKGROUND: 5-ASA is a mainstay of initial induction and maintenance therapy in patients with ulcerative colitis (UC). Although often used in patients with Crohn’s disease (CD), its clinical efficacy in this condition is uncertain. An upcoming Canadian multi centre randomized controlled trial will assess the non-inferiority of 5-ASA withdrawal versus continuation in CD (STATIC Trial NCT03261206) AIMS: To determine the prevalence of 5-ASA use in patients with CD and contrast it with its use in UC in a tertiary care setting. METHODS: All patients seen at a single site IBD clinic at London Health Sciences Centre, Victoria Hospital, between January and June 2016 were reviewed. Patients were only included if they had a definite diagnosis of UC or CD. Patients with indeterminate colitis were excluded. If patients were seen on multiple occasions during the study period, characterization of their medication profile was derived from their last visit. Chi squared analysis was used for comparison of proportions. RESULTS: 575 patients were included in the analysis. Of these, 389 (67.7%) had a diagnosis of CD and 186 (32.3%) had a diagnosis of UC. 274/575 (47.6%) patients were on biologics (36.3% on anti-TNF, 7.1% on vedolizumab, 4.2% on ustekinumab). 189/575 (32.9%) patients were on immunomodulators (12.9% on methotrexate, 20% on azathioprine). 50/575 (8.7%) patients were on corticosteroids at their last visit. 5/575 (0.9%) patients were on investigational agents. 175/575 (30.4%) patients were on 5-ASA. When broken down according to diagnosis, 134/186 (72.0%) of patients with UC were taking oral and/or rectal 5-ASA while 41/389 (10.5%) of CD patients were taking this class of medication (p

Summary Background Some patients with ulcerative colitis (UC) require immunosuppressants as maintenance therapy. Aim To assess epidemiological, clinical and disease factors at diagnosis that predict immunosuppressant use in UC. Methods All UC patients diagnosed between 1992 and 2005 and currently managed in the inflammatory bowel disease (IBD) clinic were included. Forty-three patients who currently or previously received azathioprine (AZA) or mercaptopurine (MP) for UC were compared with 130 controls. Charts were reviewed and logistic regression analyses were applied to identify factors associated with AZA or MP use. Results In univariate model, seven factors at diagnosis correlated with AZA use: male gender [odds ratio (OR) 2.2]; left-sided or extensive colitis or pancolitis (OR 8.7–14.1); systemic steroid use within the first 6 months of diagnosis (OR 5.1); more than 10 bowel movements daily (OR 6.4); persistent or mostly blood in stool (OR 2.8); endoscopic proven moderate to severe disease (OR 7.2–12.0) and requirement of hospitalization (OR 2.7) on diagnosis. In multivariate model, the first three factors were shown to be statistically significant. Conclusion Male gender, initial presentation with severe and extensive disease clinically and endoscopically, requirement of hospitalization on diagnosis or systemic steroids within 6 months of diagnosis are predictive factors for immunosuppressant use in UC.

Breast cancer resistance protein (BCRP) is an efflux transporter expressed in tissues that act as barriers to drug entry. Given that single nucleotide polymorphisms (SNPs) in the ABCG2 gene encoding BCRP are common, the possibility exists that these genetic variants may be a determinant of interindividual variability in drug response. The objective of this study is to confirm the human BCRP-mediated transport of sulfasalazine in vitro, evaluate interindividual variation in BCRP expression in human intestine and to determine the role of ABCG2 SNPs to drug disposition in healthy patients using sulfasalazine as a novel in vivo probe. To evaluate these objectives, pinch biopsies were obtained from 18 patients undergoing esophagogastro–duodenoscopy or colonoscopy for determination of BCRP expression in relation to genotype. Wild-type and variant BCRP were expressed in a heterologous expression system to evaluate the effect of SNPs on cell-surface trafficking. A total of 17 healthy individuals participated in a clinical investigation to determine the effect of BCRP SNPs on sulfasalazine pharmacokinetics. In vitro, the cell surface protein expression of the common BCRP 421 C>A variant was reduced in comparison with the wild-type control. Intestinal biopsy samples revealed that BCRP protein and mRNA expression did not significantly differ between patients with 34GG/421CC versus patients with 34GG/421CA genotypes. Remarkably, in subjects with 34GG/421CA genotype, sulfasalazine area under the concentration-time curve was 2.4-fold greater compared with 34GG/421CC subjects (P

The Canadian Association of Gastroenterology (CAG) Scholars’ Program (previously known as the Bright Lights Course) is designed to encourage trainees to consider a subspecialty career in gastroenterology. A formal analysis of the Scholars’ Program performed in 2007 revealed that 82% of participants invited to the program pursued or were planning to pursue a career in gastroenterology. The positive results are consistent with the CAG’s strategic plan of developing “the next generation of gastroenterology clinical practitioners, researchers, educators, and leaders” and to “attract, train, and retain the best and the brightest to gastroenterology”. The present study was a follow-up analysis of participants in the Scholars’ Program between 2006 and 2012. Although 93.1% of participants had an interest in gastroenterology before attending the Scholars’ Program, the majority (68.7%) reported a greater interest in gastroenterology after the program. Similar to the study from 2007, the present study again illustrates the importance and success of the Scholars’ Program in generating interest and retaining candidates in gastroenterology.

Malnutrition is common in patients with inflammatory bowel disease (IBD) and is associated with poor outcomes. Our aim is to determine if patient self-administered malnutrition screening using the malnutrition universal screening tool (MUST) is reliable by comparing patient scores with those derived from the healthcare practitioner (HCP), the gold standard.We conducted a prospective validation study at a tertiary Canadian academic center that included 154 adult outpatients with IBD. All patients with IBD completed a self-administered nutrition screening assessment using the MUST score followed by an independent MUST assessment performed by HCPs. The main outcome measure was chance-corrected agreement (κ) of malnutrition risk categorization.For patient-administered MUST, the chance-corrected agreement κ (95% confidence interval [CI]) was 0.83 (0.74-0.92) when comparing low-risk and combined medium- and high-risk patients with HCP screening. Weighted κ analysis comparing all 3 risks groups yielded a κ (95% CI) of 0.85 (0.77-0.93) between patient and HCP screening. All patients were able to screen themselves. Overall, 96% of patients reported the MUST questionnaire as either very easy or easy to understand and to complete.Self-administered nutrition screening in outpatients with IBD is valid using the MUST screening tool and is easy to use. If adopted, this tool will increase utilization of malnutrition screening in hectic outpatient clinic settings and will help HCPs determine which patients require additional nutrition support.

Summary Background Methotrexate (MTX) is administered subcutaneously to Crohn's Disease (CD) patients. There are very few studies evaluating the use of oral (PO) MTX in CD. A drug and its pharmaceutical alternative are equivalent (bioequivalence) when the bioavailability of the alternative falls within 80–125% of the bioavailability of the standard (US Food and Drug Administration - FDA). Aim To compare the pharmacokinetic (PK) profiles of PO and subcutaneous (SC) MTX in CD patients to determine the bioequivalence of these two routes. Methods Eleven patients received a PO and an SC MTX dose (25 mg) separated by one week over a two-week interval. Blood samples were collected at specified times over a 24-h period for each patient on two separate days. MTX plasma levels were obtained using sensitive mass spectrometry. Areas under the curve (AUC) were compared between the two routes. Results The mean AUC values were 3375 ng/mL × h (PO MTX) and 3985 ng/mL × h (SC MTX). The mean AUC ratio (PO/SC) was 0.86 (0.62–1.08). This correlates with a relative PO bioavailability of 86% in comparison to SC. The 90% confidence interval for the mean AUC (PO/SC) ratio is (0.785, 0.929). There were no adverse events. Conclusions The mean MTX AUC (PO/SC) in these patients falls outside the 90% confidence interval for the bioequivalence limit. SC MTX is more bioavailable than PO MTX; however, the mean relative MTX bioavailability (PO/SC) nearly met the FDA bioequivalence standard and PO MTX could be proposed in responders who would prefer this route.

Folic acid is a vitamin essential for thymidylate and purine synthesis. The human proton-coupled folate transporter (hPCFT) has recently been identified as a pH-dependent folic acid transporter, and mutations in this transporter have been linked to hereditary folic acid malabsorption. In this study, we assessed hPCFT-mediated transport activity in vitro, intersubject variability of intestinal expression in relation to blood folates, and the relationship of proton-pump inhibitor (PPI) therapy on hPCFT expression in vivo. We created a Madin-Darby canine kidney strain II (MDCKII) cell line stably expressing hPCFT to evaluate its drug substrates and inhibitors. Intestinal pinch biopsies (duodenum, ileum, colon) were collected from patients undergoing routine endoscopy procedures, and expressed levels of hPCFT were determined by RT-PCR. When assessed using MDCKII-hPCFT cells, folic acid and methotrexate were found to be high-affinity hPCFT substrates. Sulfasalazine and pyrimethamine were noted to inhibit hPCFT activity with Ki values of 42.3 and 161.7 μmol/l, respectively. hPCFT was localized to the brush-border membrane of enterocytes with highest expression in the duodenum and reduced levels in the ileum and colon. When we assessed hPCFT expression in a subset of patients who were receiving PPI therapy, a near 50% reduction in duodenal hPCFT mRNA expression was noted. These results suggest that hPCFT transporter activity can be modulated by many drugs in clinical use, and expression of this transporter in the gastrointestinal tract is higher in the duodenum than more distal sites (duodenum > ileum > colon). Importantly, we note that PPI drug use appears to be associated with reduced hPCFT expression in vivo.

OBJECTIVE: Cancer Care Ontario has recommended a program to screen for colorectal cancer using fecal occult blood testing (FOBT). Patients who test positive on FOBT will require further investigation. We examined the cost of finding an advanced adenoma in these patients using four different strategies. METHODS: Using decision analysis software (DATA 3.5, TreeAge Software, Boston, MA), we considered four strategies for evaluating patients referred for a positive FOBT: 1) flexible sigmoidoscopy to the splenic flexure, 2) flexible sigmoidoscopy with air contrast barium enema (ACBE), 3) virtual colonoscopy, and 4) colonoscopy. If an adenoma was found in any of the first three methods, colonoscopy and polypectomy were performed. An advanced adenoma was defined as a villous adenoma, tubular adenoma ≥10 mm, high grade dysplasia, or cancer. Values for probabilities, test characteristics and costs ($CDN) were estimated from a MEDLINE literature review, local costs, and OHIP fee codes. Patients with adenomas identified as well as direct medical costs from a third party payer perspective were calculated. RESULTS: Assuming a probability of adenoma of 16.9%, the cost for each strategy (compared to no investigation) was as follows: flexible sigmoidoscopy to the splenic flexure, $226; flexible sigmoidoscopy with ACBE, $424; virtual colonoscopy, $597; and colonoscopy, $387. The cost to clear a patient of adenoma(s) was $1930, $2840, $3681, and $2290, respectively. Despite being most cost-effective, the sigmoidoscopy strategy was predicted to detect 69% of cases of advanced adenomas. The radiological strategies would be less expensive if ACBE cost less than $115 or virtual colonoscopy cost less than $291. The colonoscopy strategy was more cost-effective if the probability of an adenoma was ≥33.5%. When the incremental costs were considered to investigate 1000 patients, virtual colonoscopy and sigmoidoscopy with ACBE were both more costly then colonoscopy, and neither detected as many cases of advanced adenomas. CONCLUSION: Improved access to colonoscopy seems to be the preferred approach to deal with increased referrals.

PEPTIC ULCER disease is the most common cause of acute bleeding from the upper gastrointestinal tract, accounting for 50% to 60% of cases. The vast majority of these are attributable to either the use of nonsteroidal anti-inflammatory drugs or chronic infection with Helicobacter pylori. However, any process that affects the primary lines of mucosal defense (ie, mucus and bicarbonate, intrinsic epithelial cell factors, mucosal blood flow) or repair has the propensity to induce such damage. An excellent example of such a process is the physiologic changes that occur in critically ill patients. These patients have visible signs of mucosal ischemia and in some cases increased acid outputs, which are felt to predispose to the breakdown of the integrity of the gastric mucosa and cause ulceration. Given that these documented changes appear to readily explain the pathophysiology of stress ulcer, it is perhaps not surprising that relatively little work has been performed looking at the role of other factors such as H. pylori, and even less on the value of specific therapy. In addition, though up to 5% of critically ill patient stays may be complicated by stress ulcer bleeding, the overall incidence appears to be decreasing with better supportive care and the use of ulcer-specific prophylaxis. Generally, it is rare that this complication is a major factor in a patient’s death. Studies to date have generally had large cohorts with extremely low rates of stress ulcer bleeding (1%–2%). These have failed to show a significant correlation between infection and hemorrhage. Aside from the small number of bleeds, these studies could also be criticized for using serology, a less accurate means of diagnosing active H. pylori infection, as a means of classifying patients. In this issue of the Journal of Critical Care, van der Voort et al use urea breath testing to determine the presence of active H. pylori infection at the time of emergent intensive care unit admission. Though not treated with specific H. pylori eradication nor given specific stress ulcer prophylaxis, all patients were enterally fed and given an aggressive regimen of selective gut decontamination. As with most recently published studies, the rate of clinically significant stress ulcer bleeding was extremely low (1.0%). Though both the number of unevaluable patients was high and the rate of follow-up breath testing disappointingly low because of patient discharges, it is clear from their data that this selective gut decontamination regimen is at least moderately effective in suppressing H. pylori infection. Whether the low rate of stress ulcer bleeding can be attributed to this effect or other factors, such as aggressive hemodynamic support and early enteral feeding, remains questionable. In addition, their data does not distinguish between suppression and eradication of H. pylori, a question that may have a significant impact on future patient management. Good supportive care, early enteral feeding, ulcer-specific prophylaxis, and now perhaps even selective gut decontamination may all be reasonable choices in the prevention of stress ulcer bleeding. Whether we will ever have a prospective randomized study to identify the preferred strategy will depend on the perceived magnitude of the problem and the use of these interventions on other aspects of patient outcome.