bluuebunny/crossref_metadata_2025 huggingface dataset:
A73 EVALUATING MENTAL HEALTH CONDITIONS IN YOUTH WITH INFLAMMATORY BOWEL DISEASE: A RETROSPECTIVE STUDY
Authors: Beaudoin K , Mewhinney E , Lo J , Halder S , Bortolin K , Dowhaniuk J , Issenman R , Pai N , Sherlock M , Zachos M , Grant C , Beattie K , Prowse K
Published: February 2024

Background

Adolescents with chronic disease are at increased risk of psychosocial and socio-emotional challenges. During and after the COVID-19 pandemic, an increased prevalence of mental health conditions was observed in youth with chronic conditions. It is essential to understand the prevalence of mental health conditions in youth with Inflammatory Bowel Disease (IBD) to better support, advocate, and treat mental health conditions within a pediatric healthcare setting.

Aims

We aimed to determine the number and proportion of patients with IBD at McMaster Children’s Hospital (MCH) whose medical charts have documentation of 1) a mental health condition (generalized anxiety disorder (GAD), social anxiety disorder (SAD), eating disorder, major depressive disorder (MDD), suicidal ideation, attention deficit disorder and other) and/or 2) medication(s) used to treat mental health conditions.

Methods

Patients 12-17 years old with IBD who were treated in the pediatric Gastroenterology Clinic at MCH and had at least one appointment since June 4, 2022 were eligible. Medical records were reviewed to identify documented mental health conditions and patients’ current medications. The prevalence was then determined.

Results

Of 114 patients (77 male) (mean (SD) age 15.1 (1.6) years old), 33 (29%, n=20 males) had ≥ 1 recorded mental health condition: GAD (n=27, 82%), SAD (n=1, 3%), eating disorders (n=4, 12%), MDD (n=9, 27%), suicide ideations (n=5, 15%), attention deficit disorder (n=9, 24%), and other mental health conditions (n=1, 3%). Among the 33 patients with documented mental health conditions, 19 (58%) patients were taking medications related to mental health (Table I).

Conclusions

Our results estimate a 29% prevalence of mental health conditions in youth with IBD at MCH. A lack of mental health resources and screening protocols within this setting could result in an underrepresentation of adolescents with IBD and mental health comorbidities. Future studies will focus on incorporating screening methods for mental health conditions within pediatric healthcare settings to determine current barriers and accessibility to mental health supports.

Table I. Medications in patients (n=33) with documented mental health condition

Note

Medications were prevalent in patients with ampersand:003E1 mental health diagnosis, thus frequency is lower than # of documented mental health diagnoses.

*Other mental health conditions: borderline personality disorder and bipolar disorder with depression.

Funding Agencies

None
A88 ADVERSE EVENTS ASSOCIATED WITH ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Guo H , Bishay K , Meng Z , Ruan Y , Brenner D , Forbes N
Published: February 2024

Background

Endoscopic retrograde cholangiopancreatography (ERCP) is a widely utilized procedure for diagnosing and managing various biliary and pancreatic disorders. Despite its established effectiveness, ERCP is associated with a total adverse event (AE) rate exceeding 10%. However, existing literature lacks a comprehensive synthesis of incidence rates pertaining to specific or overall AEs following ERCP procedures.

Aims

We performed separate systematic reviews and meta-analyses of (1) data from randomized controlled trials (RCTs) and (2) data from observational studies to evaluate the incidence of AEs following ERCPs in adult patients.

Methods

Two separate systematic literature searches were conducted to identify ERCP AE rates in RCTs and observational studies published between 2000 and 2021, inclusive. Abstracts underwent independent assessment to identify studies for full-text review and subsequent data extraction. DerSimonian and Laird random effects meta-analyses were applied to determine pooled incidence rates of individual post-ERCP AEs, accompanied by 95% confidence intervals (CIs). The Newcastle-Ottawa Scale (NOS) and Risk of Bias 2 (ROB2) tool were used for quality assessment of observational studies and RCTs respectively.

Results

Our analysis incorporated 242 RCTs and 143 observational studies. Among RCTs, the pooled incidences of post-ERCP pancreatitis (PEP) in patients with native and non-native papillae were 6.9% (CI 6.2% to 7.6%) and 6.1% (CI 5.3% to 7.1%), respectively. In observational studies, the pooled PEP incidences were 5.0% (CI 4.0% to 6.1%) for patients with native papillae and 4.2% (CI 3.6% to 4.8%) for patients with non-native papillae. The incidences of bleeding for patients with native papillae were 1.6% (CI 1.3% to 2.0%) and 2.2% (CI 1.2% to 3.9%) in RCTs and observational studies, respectively. The incidences of perforation for patients with native papillae were 0.3% (CI 0.2% to 0.4%) in RCTs and 0.5% (CI 0.3% to 0.7%) in observational studies. The incidence of cholangitis was 1.4% (CI 1.1% to 1.9%) in RCTs and 1.1% (CI 0.7% to 1.7%) in observational studies.

Conclusions

This meta-analysis offers comprehensive insights into the incidence of ERCP-associated AEs from 2000 to 2021, both in idealized study settings where procedures are performed by experts, and in ‘real world’ settings. More precise estimates of ERCP-related AEs can help facilitate patient consent, manage appropriate patient expectations, and enhance peri-procedural care.

Funding Agencies

None
A89 LIVER TRANSPLANT REFERRAL PATTERNS FROM THE ATLANTIC CANADIAN PROVINCES
Authors: Harper C , Allen S , Zhu J
Published: February 2024

Background

End-stage liver disease (ESLD) is one of the leading causes of deaths in Canada. Liver transplantation (LT) is the ultimate treatment option for patients with ESLD. A variety of factors may influence patient outcomes before a liver transplant is offered. There have been no studies looking at the characteristics of patients referred for LT in Atlantic Canada at the prelisting and wait-listing stages.

Aims

To examine various patient characteristics, including age, sex, MELD score, BMI, rural vs. urban residency, and diagnosis that may be important to the LT work up process. To better understand referral patterns and potential barriers to LT in Atlantic Canada including geographic factors, the COVID-19 pandemic, and the evolution of underlying liver disease.

Methods

This is a retrospective cohort study using Multiorgan Transplant (MOTP) database to identify all active referrals sent to the Atlantic liver transplant program from four Atlantic Canadian provinces between January 1, 2017 and September 30, 2023.

Results

There were 533 LT referrals to the MOTP in the observation period. From the listed patients (217), 60% were transplanted and 25% died on the waiting list. Of the patients that did not progress to being listed (56%), 197 (37%) of the referrals were withdrawn and 99 (18.6%) died prior to being listed.

There was no significant difference in mean BMI, age, listing MELD-Na, or diagnosis (p=0.35) among active referrals between pre-COVID-19 (Jan.1 2017-Mar.30 2020) and COVID-19 periods (Apr.1 2020-Sept.30 2023). There was 6% reduction in referral number from all Atlantic provinces in COVID vs. pre-COVID period, and 25% reduction in referrals for hepatocellular carcinoma (HCC) in COVID.

The ratio of patients ampersand:003C 65 yrs to ampersand:003E/= 65 yrs decreased during COVID (2.88) compared to pre-COVID (3.57). For pre and post COVID period, there were similar numbers of patients withdrawn/died prior to listing (54.7%, 54.8%). There were less patients listed (43.0%, 38.2%) and a decrease in patients transplanted (32%, 28%) pre and post COVID.

We analyzed the number of referrals from urban and rural areas. Overall, 33% of referrals were urban and 67% of referrals were rural based on patient residence. The ratio of rural to urban area referrals was 1.80 pre COVID and 2.24 during Covid, indicating an increasing number of referrals from rural centers post-COVID.

Conclusions

Although there was a robust number of LT referrals during the pandemic, there was a decrease in number of referrals and transplants after COVID. There is a notable decrease in referrals for HCC after COVID. One plausible reason is reduced HCC surveillance during the pandemic. There was an increase in referrals from rural areas during COVID. Further analysis will be needed to determine any factors that affect LT referral patterns., with the goal of identifying reasons for this change and making appropriate recommendations to the MOTP.

Funding Agencies

None
A91 PYOGENIC LIVER ABSCESSES DUE TO FUSOBACTERIUM NUCLEATUM ARE ASSOCIATED WITH SEVERE INFLAMMATORY RESPONSE AND ACUTE LIVER FAILURE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Hossein-Javaheri N , Cloutier M , Dennis C , Ramesh M , Singh I , Aijaz A , Gohil H , Miranda C J
Published: February 2024

Background

Pyogenic liver abscesses (PLAs) are uncommon entities with potentially devastating consequences requiring early diagnosis and treatment. Fusobacterium nucleatum is an anaerobic, gram-negative bacterium that is a rare cause of liver abscesses. F. nucleatum initiates a severe pro-inflammatory cascade that promotes abscess formation through the gut-liver axis especially when the gastrointestinal (GI) barrier is compromised.

Aims

In this study, we explore the characteristics of PLAs due to F.nucleatum, including the duration and mode of therapy. This may inform clinical decisions when treating persons with suspected F.nucleatum PLAs and improve mortality.

Methods

A systematic literature search was conducted in MEDLINE, PubMed, and the Cochrane Library, from 1977 to September 2023. We included full-text abstracts and articles written in English that reported patients with F.nucleatum PLA aged ampersand:003E18. Demographics, history of GI diseases, pertinent laboratory markers, abscess characteristics, and the approaches taken to treat the abscess were collected. Pooled data were assessed qualitatively and reported as mean±SEM when appropriate.

Results

We included 32 studies. The mean patient age was 52±20 years with 71% being male. In total, 47% of patients had a recent history of GI disease: sigmoid diverticulosis (n=6), colonic adenomas (n=5), duodenitis (n=2), appendicitis (n=1) and ulcerative colitis (n=1). On presentation, only 53% (n=17) reported abdominal pain. Labs were significant for leukocytosis at 22±2 K/µL, C-reactive protein 199±37 mg/L, aspartate transferase (AST) 128±24 U/L, alanine aminotransferase (ALT) 116±16 U/L, Alkaline phosphatase (ALP) 275±35 IU/L, and bilirubin 11±3 mg/dL suggestive of severe inflammatory response and cholestatic liver injury. The average abscess size was approximately 10.2±0.7 cm, 28% of which had loculations (n=9) requiring multiple drainages (n=7) or laparoscopy (n=2). The initial antibiotic of choice was piperacillin/tazobactam (Zosyn) (n=12), ceftriaxone + metronidazole (n=7), Ampicillin/Sulbactam (Unasyn) (n=5), followed by Meropenem, Metronidazole, and Ciprofloxacin. The estimated length of stay was 23±4 days with a need for long-term antibiotic therapy (54±10 days) upon discharge. The majority of patients were discharged on Metronidazole (n=11), or Amoxicillin/Clavulanic acid (Augmentin) (n=6). With appropriate source control, the estimated survival was 91% (n=29).

Conclusions

Our findings suggest that PLAs due to F.nucleatum are associated with large abscesses, a severe inflammatory response, cholestatic liver injury, and prolonged hospitalization. Multiple drainages with targeted gram-negative coverage may be required for adequate source control and favorable outcomes.

Funding Agencies

None
A113 COVID-19 VACCINATIONS IN IBD PATIENTS: PATIENT KNOWLEDGE AND PERCEPTIONS
Authors: Saunders A , Hill L , Armstrong D , Marshall J , Narula N , Pai N , Chauhan U
Published: February 2024

Background

The IBD population has historically suffered from a below average uptake of vaccinations which raises concern for COVID-19 vaccine acceptance in this population. Patients report IBD-specific reasons for COVID-19 vaccine hesitancy including fear of vaccine-related IBD flare up, a desire for IBD-specific data regarding COVID-19 vaccine safety and efficacy, and worry about current drugs affecting vaccine efficacy. Additionally, IBD patients tend to report greater fear of COVID-19, concern about the impact of their medications on COVID-19 disease, and overall need for COVID-19 information.

Aims

To explore patients’ education, knowledge, and perceptions of COVID-19 vaccination with the aim of lowering COVID-19 vaccine hesitancy, improving knowledge of COVID-19 vaccines, and identifying outstanding barriers to COVID-19 vaccination uptake.

Methods

Study participants are patients diagnosed with IBD recruited from the Adult IBD Clinic at McMaster University Medical Centre between June 2022 and May 2023. Quantitative questionnaires were distributed to participants following receipt of informed consent at routine clinics and were offered in paper format. To describe the study population, the following descriptive statistics were performed: means and standard deviation for continuous variables, distributions (n, %) for dichotomous and categorical variables.

Results

In total, 236 participants were surveyed. The sample is predominantly female (61%) and most participants are diagnosed with Crohn’s disease (63.9%). The vast majority of patients have received at minimum 1 dose of a COVID-19 vaccine (92.1%). Reported reasons for vaccination included COVID-19 vaccine being available free of cost (52.3%), recommendation from a healthcare professional (51.9%), and feeling as though the benefit of the vaccine outweighs the risks (51.6%). Most patients reported having heard of negative vaccine experiences online (75.8%) including mild (27.6%) and severe (30.8%) adverse reactions. Despite this, participants viewed vaccines as effective (83%), protective towards the individual (75.5%), and safe (68.1%). Healthcare providers were regarded as a very significant influence in terms of COVID-19 vaccine information (65.6%) and were overwhelmingly viewed as a more reliable source than mass media (91.3%). Participants did not perceive an increased risk of COVID-19 infection, COVID-19 related serious illness, or COVID-19 vaccine related adverse effects due to their IBD or IBD treatments. Participants also did not show reluctance to vaccinate due to their IBD or IBD treatments.

Conclusions

The present study provides insight into the perceptions and knowledge of Canadian IBD patients as it relates to COVID-19 vaccines. Importantly, the results highlight the crucial role of the healthcare provider on vaccination uptake and acceptance.

Funding Agencies

None
A118 THE IMPACT OF HOMELESSNESS ON ENDOSCOPY UTILIZATION, SURGICAL TREATMENT, AND POST-OPERATIVE COMPLICATIONS AMONG HOSPITALIZED PATIENTS WITH CROHN’S DISEASE
Authors: Youssef M , Mungle T , Charu V , Okafor P
Published: February 2024

Background

Homelessness is an important public health issue with a prevalence around 4.2% in the United States. Homelessness has been associated with lack of access to healthcare services, poor quality of care, and negative health outcomes. However, there is limited data on clinical outcomes among homeless individuals with Crohn’s disease (CD).

Aims

In this study, we examine inpatient outcomes including endoscopy utilization, surgical treatment, and post-operative complications among homeless patients with CD.

Methods

The Healthcare Utilization Project (HCUP) State Inpatient Databases from New York, Arizona, Massachusetts and Florida for 2013 and 2014 were used to identify adults ≥18 years admitted with CD identified by International Classification of Diseases, Ninth Revision codes. Homeless patients were then identified, and propensity score matched using a one-to-ten greedy nearest-neighbor approach to non-homeless patients to balance the distribution of baseline covariates. Differences in outcomes including endoscopy utilization, surgical treatment and post-operative complications were reported as odds ratios (ORs) and 95% confidence intervals (CI).

Results

A total of 70,457 CD hospitalizations were identified, of which 469 (0.6%) were associated with homelessness. We matched 440 homeless patients with 4,400 housed patients with CD. Homeless individuals had a higher proportion of males (p=0.002), tended to be older (p=0.035), and had more comorbidities than non-homeless individuals. There was no difference in mortality between non-homeless and homeless patients (OR 1.6, 95% CI 0.72-3.57). Endoscopy utilization was comparable between non-homeless and homeless patients with CD including gastroscopy (OR 0.71, 95% CI 0.40-1.18), colonoscopy (OR 0.80, 95% CI 0.31-1.69), and sigmoidoscopy (OR 0.37, 95% CI 0.02-1.74) [Figure 1]. Surgical treatment was also comparable, except for lower rates of bowel resection among homeless patients (OR 0.55, 95% CI: 0.29-0.93). The two groups also had similar rates of post-operative complications including pulmonary, cardiovascular, gastrointestinal, and infectious complications (Figure 1).

Conclusions

Homeless patients with CD have comparable endoscopy utilization and surgical treatment as non-homeless patients, except for lower bowel resection rates. Postoperative complications are also similar between the two groups. Future studies are needed to better understand the impact of homelessness on health outcomes and healthcare service utilization among patients with CD.

Figure 1. Endoscopy utilization, surgical treatment, and post-operative complications among homeless and non-homeless individuals using 1:10 propensity matching

Funding Agencies

None
A121 CROSS-SECTIONAL STUDY OF RESIDENT PHYSICIAN KNOWLEDGE AND PERCEPTIONS REGARDING NON-ALCOHOLIC FATTY LIVER DISEASE IN CANADA
Authors: Zhu K , Jogendran M , Zhang Y , Hussaini T , Chahal D , Yoshida E
Published: February 2024

Background

Non-alcoholic Fatty Liver Disease (NAFLD) is a prevalent condition affecting approximately 25% of the Canadian population and is projected to continue increasing. Given the increasing prevalence and complications of NAFLD, it is imperative for future primary care physicians to possess a thorough understanding of NAFLD to enhance patient care.

Aims

To assess the knowledge and perceptions of primary care resident physicians in Canada concerning NAFLD.

Methods

We conducted a nationwide cross-sectional survey of resident physicians in primary care specialties to assess their knowledge of NAFLD. Additionally, we evaluated resident perceptions regarding the importance of NAFLD and their exposure and familiarity with the condition. "Reasonable knowledge" was defined as correctly answering more than 50% of the questions. We assessed associations using χ2 testing and multiple logistic regression analysis.

Results

We received 413 responses, with 252 (61%) from family medicine residents and 161 (39%) from internal medicine residents. Among the respondents, 90% considered NAFLD an important public health issue, but only 7% felt they had adequate exposure to the condition, and 94% expressed a need for more teaching. 59% indicated that they were only slightly familiar or unfamiliar with NAFLD. The majority of respondents correctly identified diabetes (90%), dyslipidemia (96%), and obesity (97%) as risk factors for NAFLD, while fewer recognized obstructive sleep apnea (53%), hypothyroidism (27%) and hypopituitarism (14%) as risk factors. Cardiovascular disease and cirrhosis were reported as the most common causes of mortality from NAFLD by 37% and 35% of respondents, respectively. Up to 59% of respondents reported that non-alcoholic steatohepatitis can be diagnosed through imaging or a blood test. Respondents demonstrated a strong understanding of nonpharmacologic therapies, but only 11% recognized that there are no approved medications for NAFLD.

Overall, 35% of the respondents displayed a reasonable knowledge of NAFLD. In univariate analysis, factors associated with greater NAFLD knowledge included internal medicine residency (P=0.001), higher post-graduate year (P=0.003), prior GI or hepatology rotations (P=0.003), and subjective familiarity with NAFLD (Pampersand:003C0.001). However, only higher post-graduate year (P=0.048) and subjective familiarity (P=0.003) remained statistically significant in multivariate analysis.

Conclusions

Resident physicians perceive NAFLD as an important health issue but significantly lack exposure and knowledge about the condition. Further emphasis and education are needed to bridge these knowledge gaps and improve patient outcomes.

Funding Agencies

None

Endoscopy, Technology & Imaging
A140 DELAYED BLEEDING POST-ENDOSCOPIC AMPULLECTOMY FOR AMPULLARY ADENOMAS: INCIDENCE, RISK FACTORS AND MANAGEMENT OF DELAYED BLEEDING
Authors: Pawlak K , Khalaf K , Gupta S , Tham D , Mosko J , May G , Calo N
Published: February 2024

Background

The duodenal tumors of major papilla account 10% of all peri-ampullary lesions, and the majority represent adenomas, carrying malignant potential through the well-known adenoma–carcinoma sequence ([i]). Historically, surgical resection was the standard of care, but it is associated with significant risk of complications (44.7%) ([ii]). Hence, endoscopic ampullectomy became the treatment modality for selected cases. Despite the significantly lower rate of adverse events, pancreatitis and bleeding occurs in up to 25% of patients ([iii]). The rate of bleeding may be even higher, depending on periampullary lesion size and type. Factors related to delayed bleeding are poorly understood.

Aims

The aim of our study was to determine predicting factors for delayed post-ampullectomy bleeding.

Methods

We conducted a single-center retrospective study over 13 years (2010-2023). All patients who underwent an endoscopic ampullectomy were analyzed. The primary endpoint was the incidence of delayed bleeding, which was defined as a post-procedural bleeding that necessitated either a blood transfusion, ICU admission or re-intervention. Secondary outcomes included risk factors for delayed bleeding, management, and other adverse events.

Results

113 patients underwent endoscopic papillectomy [mean age 66.2 ± 12.2 years; male gender 51 (45.1%)]. Mean lesion size was 27.0 ± 14.3 mm and mean procedure duration was 62.8 ± 35.6 minutes.

There were 24 cases of delayed bleeding (21.2%). Of these, 6 (25%) required repeat endoscopic intervention. The average length of hospital was longer in those experiencing a delayed bleed (8.6 ± 4.9 vs 4.8 ± 2.4 days, Pampersand:003C0.001).

By univariable logistic regression, the odds of delayed bleeding were greater in those with hypertension (OR 3.8, 95%CI 1.4-10.3, P=0.008) or an INR ≥ 1.2 (OR 13.3, 95%CI 3.0-58.3, P=0.001). A multivariable logistic regression analysis revealed that INR≥ 1.2 predicted delayed bleeding, with an OR of 16.1 (95%CI 3.0-85.4, P=0.001). Other adverse events included perforation (n=7, 6.3%) and pancreatitis (n=19, 16.8%). There were no deaths.

Conclusions

Post-ampullectomy bleeding is a common adverse event in patients undergoing ampullectomy leading to more prolonged hospital stay. History of hypertension and elevated INR above 1.2 might be related to delayed post-ampullectomy bleeding. Additional strategies to reduce post-ampullectomy bleeding should be explored.

Funding Agencies

None
A143 PATIENT POSITION AND ENDOSCOPIC CHOLANGIOPANCREATOGRAPHY (ERCP) TECHNICAL SUCCESS AMONG PATIENTS WITH SURGICALLY ALTERED FOREGUT ANATOMY: A RETROSPECTIVE ANALYSIS
Authors: Scaffidi M , Khalaf K , Pawlak K , Chopra D , Tham D , Malipatil S B , Gimpaya N , Chan B , Yeung E , Forbes N , Calo N , Mokhtar A , Na C , Mosko J , May G , Grover S
Published: February 2024

Background

Patients with surgically altered gastrointestinal anatomy undergoing endoscopic retrograde cholangiopancreatography (ERCP) pose challenges due to anatomical distortions. Factors such as patient positioning, endoscopist experience, and choice of endoscope may influence procedural success. It is unclear how these factors may impact the technical success of ERCP among patients with altered anatomy.

Aims

We primarily aimed to determine the impact of patient positioning (prone versus left lateral decubitus [LLD]) on technical success of ERCP among patients with surgically altered anatomy. Our secondary aim was to determine the impact of patient positioning on procedural time and immediate bleeding.

Methods

We conducted a retrospective single-centre study using data from 2010 to 2020 that included patients with hepaticojejunostomy, Roux-en-Y anastomosis, Billroth-1, or Billroth-2 anatomy. The primary outcome was technical success of the ERCP, which we comprehensively defined as of successful navigation to the papilla or surgical anastomosis, selective cannulation and cholangiography, and the realization of the intended therapeutic goals. The secondary outcomes were the presence of immediate bleeding and procedural time. Statistical analysis involved descriptive statistics using mean and standard deviation (SD) and Fisher exact test with relative risk (RR) and 95% confidence interval (95% CI). All statistical tests were two-tailed and considered significant at Pampersand:003C0.05.

Results

Among 205 patients, there were 179 (87.3%) in the LLD group, and 26 (12.6%) in the prone group. There were no statistically significant differences between the two groups in terms of patient sex, age, type of altered anatomy, or American Society of Anesthesiologist (ASA) classification. We found that there was no significant differences between the two groups in terms of procedural success (RR 1.1, 95% CI: 0.8-1.5), immediate bleeding (RR 1.7, 95% CI: 0.2-14.8), and procedural time (P=0.808).

Conclusions

We did not find that patient positioning had a significant impact on technical success in ERCP among patients with surgically altered anatomy. The choice of positioning should be tailored to individual patient and endoscopist factors, with a focus on optimizing outcomes in this complex patient subset.

Funding Agencies

None
A149 SAFETY AND EFFICACY OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ESOPHAGOGASTRIC NEOPLASMS IN A CANADIAN SETTING
Authors: AlDarwish A , Bechara R
Published: February 2024

Background

Endoscopic submucosal dissection (ESD) is a technique that has been developed in Japan and is increasingly being adopted by western countries for treatment of superficial gastrointestinal neoplasms.

Aims

In this study, we aim to present the safety and efficacy of ESD for esophageal and gastric neoplasms in a Canadian setting, given the limited data regarding the outcomes of ESD in North America

Methods

Data of 100 patients with superficial upper GI neoplasms (esophageal and gastric) who underwent ESD between 2016 and 2022 in Kingston Health Sciences Centre, a tertiary hospital in Kingston, Ontario, were retrospectively reviewed. Demographics and lesion characteristics, ESD technique, and outcomes in terms of efficacy and safety were analyzed.

Results

100 patients were included in the study. 67% of the lesions were esophageal. The median diameter was 4.6cm and median area was 11.94cm2. Outcomes were favorable with technical success 98%, en bloc resection 96%, R0 resection 89% and curative resection 80%. Upstage in pathology from index biopsy was seen in 42% of the lesions. Adverse events were infrequently encountered (8%) and included delayed bleeding, aspiration, and pain.

Conclusions

ESD is a safe and effective modality for accurately diagnosing and treating early and superficial esophagogastric neoplasms when performed by trained endoscopists. Further research is required, however, to increase the adoption of this technique across Canada.

Procedural Details

Funding Agencies

None
A150 DEVELOPMENT OF MIMETIC MATRICES AS INSTRUCTIVE ORGANOIDS MICROENVIRONMENT FOR THE STUDY OF COLONIC DISEASES
Authors: Bat V , Jones C , Boudreau F , Faucheux N , Perreault N
Published: February 2024

Background

The functional complexity of the colonic epithelium is dependent on its interaction with the microenvironment involving gradients of soluble factors, extracellular matrix (ECM) proteins and stiffness. The influence of dynamic changes in the ECM has been observed in tumours, with variations in protein expression and rigidity. Their biomolecular impacts on epithelial cell behaviour are less studied due to the structural complexity of the matrix. Organoids offers a novel approach for the study of ECM biodynamics, as they require a matrix (Matrigel) to develop. Previous work showed that it is possible to grow organoids in hydrogels other than Matrigel. To evaluate the effect of matrix composition alteration on cancer initiation, we developed biofunctionalized composite hydrogels that mimic the ECM changes (chemical and physical) observed in the BmpR1a-deficient telocytes Foxl1 + (Bmpr1a△Foxl1+) mouse model of colorectal cancer (CRC) initiation.

Aims

The development of mimetic matrices, in association with organoids, would enable us to uncover the impact of matrix deregulation on colonic cells behaviour in pathogenesis process.

Methods

These hydrogels were made of alginate and 8-arm polyethylene glycol- vinyl sulfone (PEG) macromers bearing cysteine residues (CYS) and peptides. Four peptides derived from fibronectin, laminin 111, collagen I and collagen IV were used to mimic the ECM changes in the Bmpr1a△Foxl1+ colon. The grafting of CYS on alginate or peptides on PEG macromers was first characterized by thiol quantification assays. The non-grafted peptides were also analysed by uHPLC. Stiffness of the hydrogels was then determined by dynamic mechanical analysis. Finally, normal mouse organoids were seeded on hydrogels and evaluated for survival by live/dead labeling and proliferation by Alamar blue assays. Matrigel was used as a control.

Results

Chemical characterization revealed that CYS were grafted onto the alginate chain at around 190 μmol/g alginate. The PEG macromers were functionalized with four peptides at concentration varying from 0.25 to 1.5 mM. Rigidity of the hydrogels depends on the concentration of alginate used where lower concentration leads to soft matrix (0.5 kPa, homeostasis) and high concentration produced a stiff matrix (4 kPa, diseased). Organoids seeded in these mimetic composite hydrogels survived and proliferated in comparison to alginate alone.

Conclusions

Our results indicate that we can develop mimetic composite hydrogels where colon organoids can survive and thrive. This is a breakthrough model for defining the roles of ECM mechanical and biochemical stimuli in epithelial behaviour during the initiation and development of CRC.

Funding Agencies

CIHR
A161 IMPACT OF EARLY-ONSET COLORECTAL CANCER ON DISABILITY-ADJUSTED LIFE YEARS IN CANADA: 1990 TO 2019
Authors: Stukalin I , Gupta M , Buhler K , Ma C
Published: February 2024

Background

Colorectal cancer is the third most common malignancy and remains a leading cause of potentially preventable morbidity and mortality. Early-onset colorectal cancer (EOCRC) is a growing public health focus, particularly in North America, where incidence rates have increased over time.

Aims

Recognizing that EOCRC affects patients in the prime of their life, we aimed to estimate the impact of EO-CRC on disability-adjusted life years (DALYs) lost in Canada between 1990 and 2019.

Methods

We used the Global Burden of Diseases (GBD) Study to assess temporal trends in incidence, mortality and DALYs for EOCRC (patients ampersand:003C50 years old) in Canada between 1990 and 2019. Point estimates are available from http://ghdx.healthdata.

org/gbd-results-tool. Rates were estimated per 100 0000 individuals at risk and stratified by age and sex. Annual percentage changes (APC) were estimated using joinpoint regression with 95% confidence intervals (CIs).

Results

In 2019, the incidence, mortality and corresponding DALYs rates for EOCRC were 15.67 (95% CI 11.58, 20.81), 3.19 (95% CI 2.81, 3.61), and 161.88 (95% CI 142.50, 183.53) per 100,000 individuals, respectively. Overall incidence increased significantly during the study period by 1.12%/year (95% CI 0.91%, 1.62%). An analysis of the temporal trends demonstrates that the most significant increase in incidence in EOCRC occurred between 2000 - 2006 with an APC of 3.19% (95% CI 2.40%, 3.99%), which was primarily driven by an increased incidence in men. Mortality (APC 3.30%, 95% CI 2.41%, 4.19%) and DALYs (APC 3.28%, 95% CI 2.34%, 4.22%) for EOCRC also significantly increased for males between 2001 - 2006.

Conclusions

Our study reveals a substantial burden in early-onset colorectal cancer in Canada, with a significant increase in incidence over time and over 160 DALYs/100,000 population.

Figure 1: Incidence (A), Mortality (B) and DALYs (C) for EOCRC in Canada between 1990 and 2019 with 95% CIs.

Funding Agencies

None
A163 CATCHING CANCERS EARLY? AGE AND STAGE AT DIAGNOSIS OF COLORECTAL CANCER IN FIRST NATIONS PEOPLE IN ONTARIO COMARED TO OTHER ONTARIANS
Authors: Tinmouth J , Sutradhar R , Liu N , Senese L , Leylachian S , Chiarelli A , Kewayosh A , Kupets R , Tammemagi M , Sheppard A
Published: February 2024

Background

Historically, Indigenous peoples in Canada were at lower risk for cancer compared to non-Indigenous people. Data from prior to 2010 suggested that First Nations in Ontario had higher incidence & poorer survival from colorectal cancer (CRC). The current project arose from concerns raised by Indigenous partners about community members being diagnosed with colorectal cancer before screening age-eligibility.

Aims

To examine the age & stage at CRC diagnosis among First Nations people in Ontario (FN) compared to other Ontarians (ON).

Methods

With Indigenous partner support, approvals were obtained to link health administrative datasets at ICES & Ontario Health. Among others, these datasets included the Ontario Cancer Registry & the Indian Register System, a registry of FN with status, meaning they are on the official record of persons registered under section 6 of Canada’s Indian Act. We created cohorts of FN & ON aged 18-85 from 2000 to 2018, matched 1:5 on sex, age at & year of inception. For the primary analysis, we performed survival analysis, accounting for the competing event of death & using attained age as a time scale. The primary outcome was CRC diagnosis, the primary exposure was FN vs ON & we adjusted for regular screening test use, comorbidity, remoteness & having a regular primary care provider. Similarly, we examined stage at diagnosis, restricting the cohort to 2007+ due to limitations in the stage data.

Results

Baseline demographics for the 153,300 FN & 766,500 ON included are in the Table. Median (IQR) follow-up was 17 (8-20) & 18 (I8-20) years for FN & ON, respectively (p ampersand:003C0.001). There were 1,156 (0.8%) & 4,249 (0.6%) CRCs diagnosed in FN & ON, respectively (p ampersand:003C0.001). 11,213 (7.3%) FN & 25,732 (3.4%) ON died from other causes (p ampersand:003C0.001). After accounting for the competing event of death, FN were significantly more likely to be diagnosed with CRC at a younger age (HR 1.42, 95%CI: 1.32-1.53) (see Figure) & later stage (HR 1.53, 95%CI: 1.34-1.75) than ON.

Conclusions

FN with CRC were younger & presented at a later stage compared to ON with CRC. These findings have important implications for CRC screening recommendations for First Nations people in Ontario.

Baseline characteristics at cohorts inception

IQR, interquartile range

A. Cumulative incidence of colorectal cancer (primary event) & death (competing event), comparing First Nations (FN) and other Ontarians (ON). B. Focus on cumulative incidence of colorectal cancer (death as competing event, not shown), comparing FN and ON.

Funding Agencies

CIHR
A171 A MISSENSE MUTATION IN FCGBP, A STRUCTURAL COMPONENT OF MUC2 MUCUS, ALTERS THE GLYCOMICS PROFILE AND FUNCTION OF COLONIC MUCUS
Authors: Gorman H , Moreau F , Zandberg W , Bergstrom K , Chadee K
Published: February 2024

Background

MUC2 mucin produced by colonic goblet cells, form a mucus bilayer that provides a physical barrier between potential pathogens in the lumen and the underlying epithelial cells. Mucus is thus the first line of innate host defense in the gastrointestinal (GI) tract. Many GI diseases including inflammatory bowel disease and colon cancer affect the glycosylation of mucus. Goblet cells produce a variety of proteins that are associated with the mucus layer. Of these proteins, FCGBP is of significant interest due to its structural similarities to MUC2 mucin with unknown functions. In this study, we investigated if a missense mutation in FCGBP altered the glycosylation of goblet cell MUC2 and affected its barrier functions.

Aims

Aims:

1) To determine mechanistically how FCGBP impeded the structural integrity of the mucus layer

2) To quantify MUC2 glycoprotein modifications in the altered mucus layer

Methods

To investigate whether FCGBP impaired mucus barrier functions, two cell types were investigated: wildtype LS174T (WT) MUC2 mucus-producing goblet cells and LS174T cells with a missense mutation in FCGBP (FCGBP-Mut). To determine if FCGBP-Mut led to loss in barrier function in the mucus layer, the penetration of 0.2, 1, and 2 μm fluorescent beads (to mimic bacteria) through the mucus layer were quantified. To determine if the differences in penetrability were caused by differences in MUC2 glycosylation in the goblet cell lines, sensitive glycomic analyses were performed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and capillary electrophoresis with laser-induced fluorescence detection (CE-LIF). Both cells and purified MUC2 mucin granules were analyzed and confirmed by lectin binding assays. To enumerate differences in the glycomics profiles, RT-PCR was performed on over 30 human glycosyltransferases.

Results

FCGBP-Mut cells exhibited an altered glycomics profile with a significant increase in sialylated/fucosylated glycans as quantified by HPLC-MS and an increase in sialyl- and fructosyltransferase mRNA expression. In contrast to WT goblet cells, FCGBP-Mut cells exhibited significant loss in MUC2 mucus barrier function as quantified by fluorescent beads penetration through the mucus layer temporally. The altered glycosylation in FCGBP-Mut cells triggered increased metabolic stress and ROS production that enhanced susceptibility to Salmonella enterica binding, invasion and cell death.

Conclusions

This study demonstrates that a single missense mutation in FCGBP altered the penetrability of the mucus layer associated with an increase in sialylated/fucosylated glycans, a signature hallmark of numerous colonic diseases. These findings underscore the importance of FCGBP in providing structural integrity of the mucus layer and homeostatic maintenance of goblet cell glycosylation profiles.

Funding Agencies

CIHR
A178 GASTROINTESTINAL STRICTURES IN A PEDIATRIC PATIENT WITH SATOYOSHI SYNDROME
Authors: Pohoreski K , Pajunen K , Brundler M , Wrobel I
Published: February 2024

Background

Satoyoshi syndrome (SS) is a rare, progressive, multisystem disease including muscle spasms, alopecia, skeletal deformities, and diarrhea, with suspected autoimmune etiology. Treatment includes corticosteroids, immunoglobulin therapy, or immunosuppression. Reported endoscopic findings include loss of intestinal folds and nodularity in the stomach and the intestine, with histology showing gastritis cystica polyposa and lymphoplasmacytic infiltrate, as well as fibrosis noted on autopsy reports. To date, no cases of intestinal stricture have been described in SS.

Aims

To describe an original case of intestinal strictures in SS.

Methods

Case report and literature review.

Results

We present a case of a 10-year-old girl with chronic diarrhea and intermittent hematochezia, postprandial abdominal pain, intermittent non-bilious emesis, stunted growth, and weight loss, with acquired alopecia and severe muscle cramps. Examination showed a non-dysmorphic, small child with alopecia totalis and a distended, tender abdomen. Investigations demonstrated an unremarkable endocrine work-up, mild hypoalbuminemia, microcytic anemia, and anti-transglutaminase serology at 3-4x ULN with no improvement on the gluten-free diet. Endoscopy identified a duodenal stricture with a very distended stomach and duodenal bulb, mucosal nodularity and bridging creating a web-like appearance, and edema and friability of the left-sided colon. MR enterography confirmed an isolated duodenal stricture. Pathology displayed patchy fibrosis with crypt/glandular dilatation in the antrum, duodenum, and rectum. Skeletal imaging detected physeal widening and sclerosis with mild slipping of the epiphyses. Auto-immune markers included positive ENA profile for anti-Sm, anti-Sm/RNP, and anti-RNP-A. The patient was treated with corticosteroids in addition to a series of endoscopic dilatations for duodenal stricture with symptomatic benefit, with addition of upadacitinib for alopecia management. Follow-up revealed intermittent worsening of symptoms with steroid taper, necessitating further duodenal dilatations, and evidence of a new anal stricture. The patient remains on corticosteroid therapy with ongoing surveillance.

Conclusions

This case identifies the first report of intestinal strictures in SS, which may suggest that in addition to suspected autoimmune pathogenesis, disorders of fibrogenesis may need to be considered.

Funding Agencies

None
A181 EXPLORING THE ROLE OF KLEBSIELLA VARIICOLA AND KLEBSIELLA PNEUMONIAE IN PEDIATRIC ULCERATIVE COLITIS PATHOGENESIS
Authors: Arjomand Fard N , Bording-Jorgensen M , Cheng C , Kerr K , Aujla H , Mansour S , Elhenawy W , Perry T , Wine E
Published: February 2024

Background

Recent studies indicated that Klebsiella (K) pneumoniae (isolated from the stool of IBD patients) and K. variicola (isolated from the mesenteric tissue of Crohn disease patients) have the potential to induce inflammation in epithelial and preadipocyte cells, exacerbating colitis in murine models.

Aims

We isolated these strains from pediatric ulcerative colitis (UC) patients' appendix (relevant to UC pathogenesis given the protective effects of appendectomy) and other non-inflamed colon sections. We hypothesized that these isolates are invasive and induce inflammation in UC. These strains have not been previously studied in UC.

Methods

K. variicola and K. pneumoniae were isolated from two pediatric UC patients' appendices and other non-inflamed colon sections and identified using 16S DNA Sanger sequencing. Virulence of the two strains was determined by infecting Caco2 cell lines and performing adhesion and invasion assays, quantifying biofilm formation, and assessing barrier functions using transepithelial electrical resistance (TEER) measurement. Importantly, we monitored the production of pro-inflammatory (e.g., IL-8, TNF-α) and anti-inflammatory (IL-10) cytokines using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR).

Results

K. variicola and K. pneumoniae exhibited high levels of biofilm formation compared to adherent-invasive Escherichia coli (AIEC), which are commonly isolated from IBD patients. Furthermore, the Klebsiella strains adhered to epithelial cells within 2-3 hours post infection. TEER experiments showed compromised barrier integrity after 6 hours and overnight infection. Except for K. pneumoniae isolated from the ascending colon, the tested strains exhibited a significant increase in IL-8 expression. Similarly, K. variicola from the peri-appendicular region demonstrated elevated TNF-α gene expression.

Conclusions

K. variicola and K. pneumoniae isolated from UC patients have the potential to form biofilms, disrupt barrier integrity, and trigger inflammatory responses. These findings unravel a potential role for pathogenic Klebsiella strains in driving UC pathogenesis. Importantly, these data shed light on the role of appendix-associated bacteria in the development of UC. Future work includes using comparative genomics to map the virulence determinants of these bacteria.

Funding Agencies

CIHRWomen and Children's Health Research Institute (WCHRI)
A189 INVESTIGATING THE ROLE OF BACTERIAL HISTAMINE METABOLISM IN VISCERAL HYPERALGESIA
Authors: Ross T , Pujo J , Hall-Bruce M , Collins S , Vanner S , Reed D E , Bercik P , De Palma G
Published: February 2024

Background

Intestinal microbiota have been implicated in the expression of irritable bowel syndrome (IBS) as patients present with altered gut microbial profiles and microbial metabolic activity. We have previously identified bacterial histamine to strongly influence mast cell accumulation through only IBS activation of the H4 receptor, leading to visceral hyperalgesia in a subset of patients with IBS. We hypothesize that a subset of IBS patients with high histamine-producing microbiota exhibit an aberrant histamine metabolism. Investigating the microbiota-driven pathways involved in histamine metabolism is key to understanding abdominal pain pathophysiology in IBS patients.

Aims

1. To study whether variations of histamine levels are due to bacterial metabolism using in vitro and in vivo approaches.

2. To identify the prevalence of high histamine-producing and histamine-degrading bacteria in a clinical cohort via in silico analyses.

Methods

Using in vitro approaches, stool samples from healthy control (HC) donors and IBS patients were inoculated in minimal media in aerobic/anaerobic conditions, with/without excess histidine or added histamine. Bacterial histamine production and degradation were assessed in culture supernatants by ELISA. After identification through Sanger sequencing, individual colony capacity to degrade and produce histamine was assessed. Host and microbial contributions to histamine metabolism will be identified through analyses of germ-free mice colonized with IBS and HC stool samples.

Results

IBS patients (n=23) tested were found to consistently produce higher levels of histamine compared to HC (n=3). Among the tested isolated colonies from IBS patients (n=179) 61% produced histamine compared to 33% of HC (n=54), and 20% degraded histamine compared to 11% of HC. Of these colonies, 13% of only IBS isolates demonstrated the capacity to both degrade and produce histamine. Facultative anaerobes were found to possess both higher production and degradation capacity. Both pH and histamine concentration determine bacterial ability to produce or degrade histamine.

Conclusions

Based on these findings, both healthy and IBS individuals exhibit varying levels of histamine production/degradation, most prominently through facultative anaerobes. The intestinal environment and bacterial community composition are major regulators of bacterial histamine metabolism. The observed in vitro capacity to produce/degrade histamine, and its biological implications, will be confirmed with gnotobiotic humanized mice, ultimately aiding in designing microbiota-directed therapies for the management of visceral hypersensitivity.

Funding Agencies

CIHRFarncombe Innovation Fund