bluuebunny/crossref_metadata_2025 huggingface dataset:
A133 MARGIN THERMAL ABLATION WITH SNARE-TIP SOFT COAGULATION EFFECTIVELY MITIGATES RECURRENCE AFTER ENDOSCOPIC MUCOSAL RESECTION OF LARGE NON-PEDUNCULATED COLORECTAL POLYPS
Authors: Jiang S X , Zarrin A , Walia A , Galorport C , Xiong W , Enns R , Lam E , Shahidi N
Published: February 2024

Background

Recurrence following endoscopic mucosal resection (EMR) historically occurs in approximately 15-20% of large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs). Margin thermal ablation with snare-tip soft coagulation (STSC) of the post-EMR defect is an evidence-based modality to mitigate recurrence. However, international validation of margin thermal ablation outcomes is needed.

Aims

To evaluate the frequencies of endoscopic and histologic recurrence following margin thermal ablation with STSC for LNPCPs managed by EMR.

Methods

Consecutive patients ampersand:003E 18 years of age who underwent endoscopic resection for a LNPCP were enrolled in a prospective single center observation cohort study (clinicaltrials.gov ID: NCT05402696). Of those lesions which underwent successful EMR, margin STSC was applied systematically aiming to create at least a 2-3mm rim of completed ablated tissue (complete whitening). Recurrence was evaluated both endoscopically, using a standardized protocol for the post-EMR scar, and histologically.

Results

From 06/2022-09/2023, 335 LNPCPs were endoscopically resected, including 209 by EMR. Following successful EMR, 182 (87.1%) underwent margin STSC. Of these lesions, 49 LNPCPs in 46 patients were assessed at first surveillance colonoscopy. Margin STSC was complete for 44 (89.8%) lesions and incomplete for 5 (10.2%) due to difficult angulation/positioning (n=3) and ileocecal valve location (n=2). Median interval to first surveillance colonoscopy was 6 (IQR 6-7) months. There was no evidence of recurrence noted on endoscopy. Biopsy was performed in 44 (89.8%) with no evidence of histologic recurrence.

Conclusions

Thermal ablation of the defect margin with STSC effectively negates recurrence and should be considered standard of care following EMR.

Funding Agencies

None
A137 BALLOON-ASSISTED ENDOSCOPY FOR SMALL BOWEL BLEEDING – A REVIEW
Authors: Malik G , Guo J Y , Halloran B , Zepeda-Gomez S
Published: February 2024

Background

Gastrointestinal (GI) bleeding is a potentially life-threatening medical emergency requiring immediate medical attention. Obscure GI bleeding (OGIB) Is defined as GI bleeding with no obvious culprit lesion found on initial upper or lower endoscopy. Further investigations are needed as 75% of those cases originate in the small bowel. The advent of small bowel endoscopy, consisting of video capsule endoscopy (VCE) and device-assisted enteroscopy (DAE) has allowed clinicians to endoscopically visualize the entire GI tract and perform therapeutic interventions. These devices include balloon assisted endoscopy (BAE) and Spiral Endoscopy (SPE).

Aims

The objectives of this review are to analyze the definitions, etiologies, and risk factors of OGIB. Furthermore, we reviewed the diagnostic and therapeutic yields of DAE and its safety profile. Due to the adverse effects and recall of SPE, we only report here on BAE.

Methods

A literature review was conducted using PubMed and OvidSP (Medline) to identify articles on the use of VCE and DAE for OGIB. Keywords included a combination of gastrointestinal bleeding with occult, obscure, active and inactive, small bowel bleed, diagnostic yield, therapeutic yield, and rebleeding rate. The information was obtained via systematic review and meta-analysis, retrospective studies, and case reports.

Results

A total of 32 papers were reviewed. The most common causes of OGIB reported were vascular lesions (23-47%), inflammatory lesions (12-16%), and tumors (5-16%). The risk factors associated with OGIB include age, cardiac disease, liver cirrhosis, chronic kidney disease, and hereditary vascular diseases. The overall diagnostic and therapeutic yields of BAE in OGIB were 76.3% and 49.5%, respectively. Factors that increased the yield included performing an initial VCE (increase by 7%) and performing the procedure within the first 10 days after the initial bleeding episode (87.5%) as compared to after 10 days (11.1%). Recurrent bleeding can occur in up to 46% of patients. Risk factors for rebleeding include cirrhosis, overt bleeding symptoms, and presence of multiple vascular lesions. Associated adverse effects in DAE were minor in 9.1% of patients and severe in less than 2%. These include bleeding (0.8%), perforation (0.3%), and pancreatitis (0.3%).

Conclusions

OGIB is a challenging clinical entity. BAE now allows clinicians to diagnose and treat culprit lesions in the small bowel with reasonable success and a strong safety profile, however timing and prior VCE can further optimize this. Clinical decisions and follow up should be made based around existing risk stratification tools and scores. Further prospective research is needed to determine optimal timing of DAE from presentation of OGIB that would increase diagnostic and therapeutic yields.

Figure 1. A and B) Endoscopic images of small bowel vascular lesion. C) Bleeding vascular lesion treated with hemostatic clips.

Funding Agencies

None
A146 UNDERWATER EMR WITHOUT SUBMUCOSAL INJECTION FOR COLONIC ANGIODYSPLASIA
Authors: Yu R , Barclay R
Published: February 2024

Background

Angiodysplasia is a common source of overt or occult colonic bleeding. Lesions are amenable to endoscopic thermal treatment such as APC, which requires a dedicated device and carries a small risk of perforation. Underwater EMR without submucosal injection (UEMR) is safe and effective for colorectal polyps, and requires no special equipment.

Aims

This study explores the use of UEMR to treat colonic angiodysplasia. We endeavoured to assess the effectiveness of treatment with UEMR in patients with this unique condition and further quantify the safety and adequacy of the obtained sample to achieve diagnosis. Further analyses were undertaken to determine the cost-burden of this method compared to comparable methods of treatment.

Methods

Retrospective review of clinical database for patients who underwent UEMR for colonic angiodysplasia between 2021 and 2023.

Indications for treatment were iron deficiency anemia (N=4), Hematochezia (N=2), and melena (N=1).

Lesions were excised en bloc using standard UEMR technique without submucosal injection and soft-coagulation electrosurgical settings.

Results

Six patients (5 females, mean age 76 ± 10) underwent colonoscopy with UEMR for treatment of angiodysplasia. One patient with extensive lesions required two endoscopic sessions; the others were treated during a single procedure. The median number of lesions was two; range, 1 to 13). A total of 24 lesions (size 7 ± 2 mm) were treated with UEMR. All lesions were located in the proximal colon (cecum, 14; ascending colon, 10). Histology of excised specimens confirmed a diagnosis of angiodysplasia.

There were no procedural complications. Overt bleeding and anemia resolved in all patients.

Conclusions

In this series of patients, UEMR without submucosal injection was simple, safe and effective for treatment of proximal colon angiodysplasia. Advantages of this approach over conventional therapy with APC include reduced equipment needs, lower cost and histologic diagnosis. Further study comparing UEMR to conventional thermal modalities is warranted.

Funding Agencies

None
A147 FACTORS ASSOCIATED WITH PATIENT COMFORT DURING ENDOSCOPIC RESECTION OF LARGE NON-PEDUNCULATED COLORECTAL POLYPS
Authors: Zarrin A , Jiang S X , Walia A , Galorport C , Xiong W , Telford J , Enns R , Lam E , Shahidi N
Published: February 2024

Background

Patient comfort is an important quality indicator in endoscopy, as it relates to patient satisfaction and adherence with endoscopic surveillance recommendations. Endoscopic resection techniques are now the primary treatment strategy for LNPCPs. However, factors associated with patient comfort are unknown.

Aims

To assess patient comfort during endoscopic resection of LNPCPs and factors associated with discomfort.

Methods

Consecutive patients ampersand:003E 18 years of age who underwent endoscopic resection for a LNPCP were enrolled in a prospective single center observation cohort study (clinicaltrials.gov ID: NCT05402696). The St. Paul’s Endoscopic Comfort Scale (SPECS) was used to assess patient comfort (total score; vocalization, body language, anxiety sub-scores). Patient discomfort was defined as a SPECS total or sub-score above 0.

Results

Between 06/2022 - 07/2023, 258 patients underwent 276 procedures to remove 318 LNPCPs. Median age was 67.0 years and 126 (48.9%) were female. Most patients were ASA II (168, 57.3%) and 268 (97.1%) received conscious sedation with midazolam and/or fentanyl. Median SPECS score was 0 (IQR 1) with a range of 0 (145, 56.6%) to 5 (2, 0.8%). Challenging access and proximal LNPCP location were associated with overall discomfort and vocalization respectively (both p ampersand:003C 0.03). Highest rate of discomfort corresponded to lesions with difficult reach and easy positioning (70.6% of patients with these lesions had SPECSampersand:003E0). Lesion size, resection technique or resection duration were not associated with discomfort.

Conclusions

Minimally invasive endoscopic resection techniques can be performed without patient discomfort in most patients with LNPCPs. Challenging access and proximal location should be taken into consideration when administering sedation.

Funding Agencies

None

Gastrointestinal Oncology
A153 IMPLEMENTATION OF THE CHAMPLAIN REGION GASTROINTESTINAL ENDOSCOPY CENTRAL INTAKE (GICI) PROGRAM
Authors: Monod A , Jarrar M , Coates S , Burns H , Prihar R , Dubé C
Published: February 2024

Background

The Champlain region of Ontario is implementing a regional central intake triage program for screening colonoscopy services (FIT+, screening and surveillance indications). The aim of this program is to improve the delivery of regional endoscopy services, so that access to resource-intensive endoscopy procedures can be equitable, timely and evidence-based. We characterized the first phase of implementation of the Champlain Regional GI Central Intake (GICI).

Aims

The primary objective of this study is to identify program strengths and opportunities for quality improvement.

Methods

Prospective data was collected from August 1, 2022 to August 31, 2023. Descriptive statistics were analyzed. Discrete data were presented in terms of counts, percentages and means where appropriate.

Results

1942 CIP referrals were received during the period of study. 1478(76.1%) referrals were submitted by fax, and 571(29.4%) were for positive FITs. 703(36.2%) referrals were declined, with 374(19.3%) not meeting Cancer Care Ontario (CCO) referral indications, 84(4.3%) being duplicates and 56(2.9%) being symptomatic. Prior to a policy change in March 2023, 23(1.2%) referrals were declined due to incomplete referral forms. 581(29.9%) referrals indicated a preferred physician or hospital site. On average, triage decisions were made within 11.4 hours of receipt of referrals for positive FIT, and 6.8 days for other indications. The average time from FIT positivity to referral receipt at CIP was 20.0 days. In the first quarter of 2023, 75th percentile wait times for colonoscopy were 35 days for FIT positivity, 150 days for symptoms, and 346 days for other screening indications.

Conclusions

GICI and the use of CCO evidence-based guidance reduces the need for colonoscopy in nearly 20% of referrals. It also decreases physician administrative burdens by eliminating duplicate referrals. Referrals should not be declined due to incomplete forms. Measures to improve timely access to colonoscopy for symptomatic patients should be explored. Most referred patients do not have a preferred physician or hospital site. Further primary care support and engagement is needed to encourage the use of the GICI as well as immediate referral for FIT+ colonoscopy.

Funding Agencies

None
A154 PRIMARY APPENDICEAL GASTROINTESTINAL STROMAL TUMOR (GIST) IN A PATIENT WITH DELAYED APPENDICITIS: CASE PRESENTATION AND LITERATURE REVIEW
Authors: Pacheco Blandino I I , Naser K
Published: February 2024

Background

Gastrointestinal stromal tumors (GISTs) are uncommon neoplasias, arising from mesenchymal tissue in the gastrointestinal tract. However, primary appendiceal GISTs (PA-GISTs) are rare, with less than 27 cases reported to date. Although treatable with neoadjuvant chemotherapy and subsequent resection, GISTs of the appendix can initially present with appendicitis-like symptoms, and are often treated as acute appendicitis (AA) due to initial misdiagnosis. A 75-year-old man presented to the emergency department of Brightshores Health System (BSHS) with right upper abdominal pain progressing to the right lower quadrant. He was referred to our surgical service, and his condition was treated as delayed appendicitis.

Aims

1. To raise awareness of GIST as a distinct diagnostic possibility in patients presenting with acute appendicitis (AA)-like symptoms.

2. To assess whether delayed appendectomy has an impact in the overall disease outcome for PA-GIST.

Methods

A rare case of PA-GIST was found after a retrospective review of all appendectomies performed at BSHS for appendicitis with or without neoplasia in the last 11 years. To our surprise, we uncovered a rare case PA-GIST. Comprehensive chart review was performed.

Results

A 75-year-old man presenting with a 5-day history of right upper and lower abdominal pain was clinically diagnosed with AA. CT abdomen and ultrasound showed probable appendicitis with phlegmon, distal tip inflammation, no abcess and mild left hydronephrosis. After initial antibiotics and colonoscopy, the patient underwent interval appendectomy. Pathology revealed no AA, a low-grade GIST with focal interstitial cell of Cajal hyperplasia of the distal appendix and positive margin. Six weeks later, cecectomy showed no clinicopathologic evidence of residual PA-GIST. Literature review revealed 27 other PA-GIST tumors to date. Twenty three were found incidentally through imaging, colonoscopy, or surgery. Four cases involved patients presenting with AA symptoms. Our patient was among those presenting with AA symptoms, but with no histological evidence of appendicitis in the delayed appendectomy specimen. Consistent with 25/27 cases, our patient’s GIST displayed spindle morphology, ampersand:003C5cm in size, and without atypia, mitosis, or necrosis.

Conclusions

PA-GISTs tumors are rare, with only 28 cases reported to date, including ours. Some PA-GIST tumors are found incidentally in patients that present with symptoms of AA. Although there is no concensus opinion for optimal treatment of PA-GIST, delayed appendectomy followed by cecectomy have proven to be an acceptable treatment for our patient with no evidence of recurrent or metastatic disease after 6.5 years on follow up by clinical and endoscopic surveilance.

Funding Agencies

None
A156 INCIDENCE OF MALIGNANT GASTRIC OUTLET OBSTRUCTION IN PATIENTS WITH PANCREATIC CANCER UNDERGOING FOLFIRINOX THERAPY
Authors: Rostamianmoghaddam Y , Barkun J , Qatomah A , Long C , Chen Y
Published: February 2024

Background

Malignant gastric outlet obstruction is a morbid complication of pancreatic cancer. There is currently a lack of epidemiology data characterizing its incidence and outcomes in patients with unresectable pancreatic head cancer undergoing chemotherapy with leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX). Determining the incidence of MGOO in this context is crucial for developing effective management strategies.

Aims

We aim to ascertain the incidence of MGOO in patients with pancreatic cancer treated with FOLFIRINOX. Secondary objectives include evaluating the clinical outcomes of MGOO. The primary endpoint was the rate of malignant gastric outlet obstruction, defined as clinical evidence of MGOO confirmed with axial imaging and/or endoscopy. Secondary endpoints included the length of hospitalization for MGOO and the rate of successful endoscopic or surgical management.

Methods

This was a retrospective, single-center study including patients with pancreatic head cancer treated with FOLFIRINOX between January 1, 2017, and December 31, 2022, who did not undergo surgical resection. Patients were excluded if they had pancreatic cancer located in the neck, body, and/or tail of the pancreas, had predominantly cystic cancer, had an oncological resection, had a prophylactic surgical gastrojejunostomy, or had metastatic cancer to the pancreas.

Results

Overall, 44 patients with pancreatic head cancer (40.90% female, mean age 59.3 ± 8.5 years) were included. There was no statistically significant difference in tumor staging between MGOO and No-MGOO patients: overall, 6.8% borderline, 40.9% metastatic, and 52.3% locally advanced. The incidence of MGOO in patients with pancreatic head cancer was 36.36%. Patients who never developed MGOO experienced significantly shorter unplanned hospitalizations (mean ± SD: 20.8 ± 18.30 days) compared to those with MGOO (mean ± SD: 50.33 ± 41.22 days; p = 0.0175). The mean number of FOLFIRINOX cycles received was 7.2 (±5.43) for patients without MGOO and 8.1 (±5.81) for patients with MGOO (p = 0.6152). Among patients with MGOO (n=12), management strategies included EUS-guided gastrojejunostomy (43.75%), duodenal stent placement (31.25%), and medical management (25%).

Conclusions

Our contemporary data suggest a high rate of MGOO (36%) in patients with advanced pancreatic head cancer undergoing FOLFIRINOX treatment. The development of MGOO was associated with longer total hospitalization when compared to patients who never developed MGOO. Our study underscores the significant negative impact of MGOO with further research needed to elucidate better management strategies including better endoscopic or surgical prophylactic measures.

Funding Agencies

CIHR
A160 A CASE OF BREAST CANCER METASTASIS MASQUERADING AS SIGNET RING CELL ADENOCARCINOMA OF THE STOMACH
Authors: Stephenson E , Zeman-Pocrnich C , Sey M
Published: February 2024

Background

Gastric cancer has a poor prognosis, particularly at advanced stages. Endoscopic submucosal dissection (ESD) can be used to treat selected early-stage gastric cancers. This case study explores the challenge of diagnosing and managing patients when metastatic lesions mimic primary gastric cancer, as seen in this case of breast cancer metastasis resembling signet ring cell adenocarcinoma of the stomach.

Aims

The aim of this case report is to describe an unusual case of breast cancer metastasis to the stomach identified unexpectedly on random gastric biopsies, initially diagnosed as a primary gastric signet ring cell adenocarcinoma.

Methods

Clinical and pathological records of the described patient were reviewed retrospectively. Furthermore, a review of the relevant literature was also performed.

Results

A 68 year-old-woman underwent gastroscopy for nausea and vomiting. Her past medical history was remarkable for bilateral mastectomies ten years ago for invasive lobular carcinoma, with metastatic bone disease diagnosed by imaging five years prior. She had been well controlled on letrozole taken intermittently due to side effects. At endoscopy, while the stomach appeared grossly normal, random biopsies done for Helicobacter pylori identified a single focus of signet ring cell adenocarcinoma. Subsequent chromoendoscopy identified an area of subtle mucosal abnormality for which the patient declined surgery and was instead managed by ESD which surprisingly yielded no dysplasia. A follow up gastroscopy with random biopsies also failed to identify any areas of dysplasia, but random biopsies on a subsequent gastroscopy again identified a minute focus of adenocarcinoma with signet ring cell morphology. Given the unusual presentation of apparent signet ring cell adenocarcinoma in two distinct areas in the stomach without any visible endoscopic abnormality an in-depth pathological analysis was conducted. By immunohistochemistry the tumor cells stained positive for Estrogen Receptor, GATA3, and CK7 and negative for antibodies targeting CK20 and CDX2, which supported an interpretation of minute multifocal breast cancer metastases to the stomach from hematogenous spread.

Conclusions

In this case, repeated endoscopic investigations and immunohistochemical staining revealed minute multifocal breast cancer metastases to the stomach. Conventional tumor staging methods often cannot identify microscopic metastases, potentially impacting disease progression and patient care. A high level of suspicion for metastatic breast cancer and a detailed pathological analysis allowed for the correct diagnosis in this patient.

Funding Agencies

None
A165 MALIGNANT TUMORS OF THE SMALL BOWEL DIAGNOSED BY DOUBLE BALLOON ENTEROSCOPY: A FIFTEEN-YEAR EXPERIENCE OF A MEDICAL CENTER IN MID-TAIWAN
Authors: Wu Y , Chou J
Published: February 2024

Background

The malignant tumors of the small bowel are relatively rare, and their pre-operative diagnosis is usually difficult

Aims

This study was aimed to investigate the clinical characteristics of patients with malignant small bowel tumors who underwent double balloon enteroscopy. Secondary end points were to evaluate the usefulness and safety of double balloon enteroscopy for the diagnosis of patients with suspected small bowel tumors derived from other previous procedures.

Methods

From January 2008 to June 2023, we retrospectively analyzed consecutive patients who underwent double balloon enteroscopy at a medical center in mid-Taiwan over a 15-year period (Figure 1).

Results

Double balloon enteroscopy were performed in 1001 patients. Small bowel tumors were diagnosed in 141 patients (141/1001; 14.1%), of which 76 patients (53.9%) (43 males, a mean age of 61.89 years) had malignant tumors : 37 had gastrointestinal stromal tumors (49.4%), 16 had adenocarcinoma (20.8%), 10 had metastatic cancer (13.1%), 7 had lymphoma (9.2%), 3 had angiosarcoma (3.9%), 2 had carcinoid (2.6%), and 1 had desmoid tumor (1.3%) (Figure 2).

The indications for double-balloon enteroscopy in patients with malignant small bowel tumors were obscure gastrointestinal bleeding (68.4%). The concordance rate of diagnoses based on double balloon enteroscopy with diagnoses based on small bowel barium study, computed tomography, and capsule endoscopy among patients with small bowel tumors was 54.1%, 65.9% , and 76.9%, respectively. (Figure 3, 4) .

Therapeutic plans were changed to surgery in 67.1 % of patients with malignant small bowel tumors.

Additionally, treatment was added on chemotherapy in 25.6% of patients with malignant small bowel tumors after the results of double-balloon enteroscopy.

Conclusions

Approximately 14.1% of patients who underwent double balloon enteroscopy had small bowel tumors, 53.9% of small bowel tumors are malignant. The most common indication for double balloon enteroscopy in patients with malignant small bowel tumors was obscure gastrointestinal bleeding. Double balloon enteroscopy is a very useful modality in diagnosing malignant small bowel tumors and has an important impact on therapeutic plans and clinical results.

Figure 1. The Prevalence Rate of Small Bowel Tumor

Figure 2. Malignant tumor

Figure 3. Location Distribution of Small Bowel Tumors

Figure 4. The clinical manifestations of Malignancy Tumors

Funding Agencies

None

Intestinal Disorders
A168 RATES OF CLOSTRIDIOIDES DIFFICILE INFECTIONS REQUIRING HOSPITALIZATION DURING THE COVID-19 PANDEMIC
Authors: Besney J , Buhler K , Kaplan G G , Lu C , Seow C , Novak K , Panaccione R , Ma C
Published: February 2024

Background

Clostridium difficile infection (CDI) is the most common cause of nosocomial infectious diarrhea and is associated with a substantial burden of morbidity and mortality. Most cases of CDI are acquired through health care setting contacts, where appropriate infection prevention and control (IPC) measures such as contact isolation and proper hand hygiene have been demonstrated to prevent horizontal transmission.

Aims

We aimed to evaluate whether there was a reduction in CDI-related hospitalizations during the COVID-19 pandemic when an increased emphasis was placed on maintaining IPC measures.

Methods

We analyzed data from the National Inpatient Sample (NIS) between January 2018 and November 2020. The NIS is the largest publicly available administrative health database in the United States, capturing ampersand:003E7 million hospital admissions annually. All analyses were weighted for the complex survey design of the NIS. Temporal trends in monthly admissions for patients with CDI defined using International Classification of Disease 10th revision codes and excluding patients with established CDI carrier status were evaluated using joinpoint regression. Changes over time were expressed as monthly percent change (MPC). To establish whether temporal changes were related to a reduction in CDI or whether these were more generalized effects due to the pandemic, we compared these temporal trends to rates of hospitalizations for inflammatory bowel disease (IBD) and stroke.

Results

A total of 1,501,415 CDI admissions were identified. The mean age was 64.6 years and 54.2% of patient’s were female. 4.5% of admissions for CDI were associated with in-hospital mortality. Trends in hospitalization are summarized in Figure 1. Compared to the pre-pandemic period (January 2018-December 2019) CDI-related hospitalizations decreased by 9.1%/month [95% CI: -19.2%, +2.0%] (p=0.12) in early 2020 (January-March 2020). This reduction was not sustained: hospitalizations subsequently increased by +8.0% [95% CI: -4.0%, +21.6%] (p=0.19) in mid-2020 (April-June 2020) and were stable after July 2020 (MPC -0.9% [95% CI: -3.5%, +1.7%], p=0.48). Similar patterns were observed for both IBD and stroke-related hospitalizations. Total hospitalizations per month for CDI were similar by June 2020 as compared to the year preceding the pandemic.

Conclusions

Although an initial decrease in the rates of CDI hospitalizations were seen early in the pandemic (January-March 2020), this pattern was similarly seen for other chronic and acute conditions, and this has not been sustained long-term.

Figure 1. Rates of CDI admissions (2018-2020)

Funding Agencies

None
A173 WHAT HAS CHANGED IN THE DIAGNOSIS OF CELIAC DISEASE IN CANADIANS OVER THE PAST 25 YEARS? RESULTS FROM THE STATE OF CELIAC IN CANADA SURVEY 2022
Authors: King J A , McAulay C , Secord M , Pinto-Sanchez M , Turner J , Gidrewicz D , Case S , Duerksen D
Published: February 2024

Background

Prior surveys of Canadians with celiac disease (CD) have demonstrated several challenges on the path to diagnosis. It has been over a decade since findings from the most recent survey were published.

Aims

To compare the experiences of Canadian individuals prior to CD diagnosis across time.

Methods

The State of Celiac Disease in Canada Survey is an online, nationwide survey distributed by Celiac Canada in December 2022. Over 75 questions were included, covering diagnostic pathways, presenting symptoms, and involvement of health care professionals (HCPs). Analysis was restricted to those who responded to having CD, dermatitis herpetiformis, or gluten ataxia, as well as provided the time since their diagnosis.

Results

A total of 6052 participants were included: 1210 (20.0%) were diagnosed in the last two years, 1113 (18.4%) two to five years ago, 1136 (18.8%) five to 10 years ago, 1040 (17.2%) 10 to 15 years ago, 960 (15.9%) 15 to 25 years ago, and 593 (9.8%) more than 25 years ago. Diarrhea was reported in over 70% of respondents diagnosed over 25 years ago, compared to approximately 50% diagnosed in the last five years (Figure 1A). Conversely, 31% of individuals diagnosed over 25 years ago experienced brain fog compared to 57% of those diagnosed in the last two years. Approximately 25% of respondents diagnosed at least 15 years ago experienced symptoms for more than 20 years prior, compared to 15% of those diagnosed in the last two years (Table 1). There were no clear differences in the proportion of respondents who saw a family physician before diagnosis, but there was a drop in those consulting a gastroenterologist (60% diagnosed more than 25 years ago versus 43% diagnosed in the last five years, Figure 1B).

Conclusions

Over time, there has been a shift in the clinical presentation of celiac disease, which may reflect improved detection of cases without gastrointestinal symptoms. Delays in diagnosis remain a concern but have also improved over time. The phenomenon of fewer patients consulting with gastroenterologists requires further investigation to understand the cause and impact on accurate diagnosis.

Delays in diagnosis across time since diagnosis

Note: 496 respondents did not report time from symptoms to diagnosis

Symptoms experienced (A) and healthcare professionals consulted (B) prior to diagnosis

Funding Agencies

Celiac Canada (FKA Canadian Celiac Association)
A176 RESTORATION OF IMPAIRED MICROBIOTA-MEDIATED ARYL HYDROCARBON RECEPTOR SIGNALING IN PATIENTS WITH CELIAC DISEASE BY ORAL TRYPTOPHAN SUPPLEMENTATION: AN EXPLORATORY STUDY
Authors: Kirtikar U , Rueda G H , Szeto J , Galipeau H , Constante M , Wang X , Pinto-Sanchez M , Armstrong D , Bercik P , Verdu E
Published: February 2024

Background

Celiac disease (CeD) is an autoimmune condition driven by gluten in individuals expressing celiac-specific genes (HLA-DQ2 and/or DQ8). A strict gluten-free diet (GFD) is currently the only treatment. 30-40% of celiac patients exhibit persistent symptoms despite following a GFD ampersand:003E1 year and are considered non-responsive. Tryptophan is an essential amino acid metabolized by gut microbiota to produce indoles that activate aryl hydrocarbon receptor (AhR), contributing to intestinal barrier homeostasis. Our previous study showed CeD patients have altered tryptophan metabolism and limited AhR activation, only partially improving with a GFD. In healthy volunteers, oral tryptophan supplementation improved AhR activation in the small intestine, thus, indicating its feasibility as adjuvant to the GFD in non-responsive CeD.

Aims

The study aims were to: 1) determine whether tryptophan supplementation improves celiac specific symptoms in non-responders; and 2) if tryptophan supplementation modifies gut microbiota composition, intestinal indole production and AhR activity.

Methods

The study is a double-blind, randomized, placebo-controlled trial with the aim to recruit 50 adults from the McMaster University Celiac Clinic. At visit 1, consented participants are randomized 1:1 to L-tryptophan (3g/day) or placebo and receive intervention capsules to be taken for 3 weeks after Visit 2. At Visits 2 and 3, participants complete dietary and symptom questionnaires, provide blood, stool, and urine samples, and undergo endoscopy. The primary outcome, improvement in symptoms, is assessed using the Celiac Symptoms Index (CSI); general GI symptoms by Gastrointestinal Symptoms Rating Scale (GSRS); mood symptoms by Hospital Anxiety and Depression Scale (HADS); quality of life by Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life questionnaire (PAGI-QoL).

Results

To- date we have recruited 10 participants. We will present blinded results from participants that have completed the study at the time of presentation based on responses to questionnaires pre, and post tryptophan/placebo intervention. At the time of analysis of this abstract, 5 participants had completed the study showing reduced CSI scores post intervention. The GSRS was also significantly reduced post intervention however, no change was observed in HADS and PAGI-QoL.

Conclusions

As all these results are currently blinded, we cannot attribute the symptom improvement to either tryptophan or the placebo effect. After unblinding the data, we will analyze the data to determine the extent of symptom reduction in relation to tryptophan metabolites (from urine, stool and duodenal aspirates) and AhR activation (from duodenal biopsy samples).

Funding Agencies

Weston Family Foundation
A177 AUTOIMMUNE ENTEROPATHY – AN UNCOMMON CAUSE OF MALNUTRITION
Authors: Minhas G S , Bukhari A , Tse F
Published: February 2024

Background

Autoimmune Enteropathy is a rare condition characterized by clinical symptoms of intractable diarrhea, vomiting, and weight loss that often results in malnutrition. It is associated with other autoimmune conditions from primary sclerosing cholangitis to type 1 diabetes and autoimmune thyroid disease. The epidemiology of AIE in adults is not well described. It is detailed more in the pediatric population, particularly early in life, the incidence is estimated at less than 1 in 100,000 infants.

Aims

Aims: To review a case of malnutrition secondary to Autoimmune enteropathy seen at our centre, and review the limited literature for treatment.

Methods

We did a case report presentation on an inpatient seen at our Tertiary care center in Hamilton, Ontario

We reviewed the limited literature regarding treatment of autoimmune enteropathy in adults and modelled our treatment based on this.

Results

We describe the case of a 63-year-old male in Ontario, Canada whereby he was initially diagnosed with ulcerative colitis, but did not respond to therapy – with the final diagnosis being autoimmune enteropathy. He was first consulted to Gastroenterology with colonoscopy consistent with mayo III disease, and biopsies showing chronic active colitis. He did not improve despite 5-ASA compounds, oral steroids, and trials of IV steroids. He underwent multiple admissions for chronic watery diarrhea, and subsequent treatment with IV steroids. He was started on an Infliximab biosimilar with little to no clinical response, and subsequently referral to our centre for evaluation of worsening malnutrition. Our patient’s symptoms mirrored much of what was initially described in the literature in 1985 with significant unremitting diarrhea, and dependence on TPN due to malabsorption. He underwent an EGD which demonstrated villous blunting, and apoptotic bodies – reviewed by a GI-specialized pathologist who found it was consistent with autoimmune enteropathy. His serology testing revealed a weakly positive TTG, HLA testing was completed showed a HLA DQ2 positivity and a gluten free diet was reccomended. His symptoms improved drastically from 10-12 bowels movements daily, to 1-2 daily within two weeks of treatment.

The limited literature surrounding treatment of autoimmune enteropathy was reviewed and the patient was started on oral budesonide in a tapering dose with significant clinical improvement as described in a retrospective case-control study in 2017.

Conclusions

Autoimmune enteropathy is a rare cause of malnutrition in adult patients. It is often associated with other autoimmune conditions, withsmall bowel histology showing villous atrophy, villous blunting, apoptotic bodies, and a relatively low amount of lymphocytic infiltration. The literature on treatment is limited, our patient responded to initial treatment of gluten removal for underlying celiac disease combined with oral budesonide.

Funding Agencies

None
A179 UNDERSTANDING THE NEED FOR A ZINC DIET TO TREAT ZINC DEFICIENCY IN PATIENTS WITH CELIAC DISEASE
Authors: Tandon S , Graham K , Russell L , Morgan J , Armstrong D , Pinto-Sanchez M
Published: February 2024

Background

Nutritional deficiencies in celiac disease (CeD) are caused by delayed intestinal healing and a nutrient-lacking gluten-free diet (GFD). At our specialized adult celiac clinic, zinc (Zn) was the most common deficiency present in patients and is clinically treated through Zn supplementation. However, Zn supplements in excess may cause inhibition of other minerals, and gastrointestinal side effects. Alternatively, a Zn diet may be a sustainable option to treat zinc deficiency, however patient preference regarding this treatment method is unknown.

Aims

To understand patient preference of zinc supplementation compared to a zinc diet to treat Zn deficiency in CeD. We also aim to determine the tolerability and effectiveness of Zn supplements to reduce gastrointestinal and extraintestinal symptoms in the CeD population.

Methods

This observational prospective pragmatic study was conducted from March 2022-September 2023. Eligible participants had bloodwork indicating plasma Zn levels ampersand:003C 9.4 μ/mol . All participants were prescribed 25 mg per day of Zn gluconate supplements throughout the study. Patients were provided a RedCap link where they completed questionnaires at Visit 1 and at their next clinic appointment in 3-6 months (Visit 2). These surveys included; Celiac Symptom Index (CSI) Questionnaire 2) Extraintestinal Symptoms Visual Analogue Scale (ES-VAS) and 3) Patient Perception Survey (PPS). Continuous data are expressed as Mean (SD), and categorical data is reported as frequencies (%). The Wilcoxon test was used to assess changes in symptoms.

Results

A total of 42 participants completed the Visit 1 survey, of which 17 participants had their follow up clinic appointment (Visit 2). Out of these 17 participants, 15 were female (88.2%) and the mean age was 33.7 years (+/- 10.6). The mean CSI score at Visit 1 was 35.3 (+/- 10.3) and 33.7 (+/- 13.0) at Visit 2, indicating moderate disease symptoms (p=0.552). The most common extraintestinal symptoms was anxiety (ES-VAS: 5.7), foggy mind (ES-VAS: 4.1), fatigue (ES-VAS: 4.1) and depression (ES-VAS: 3.5). There were no significant changes in extraintestinal symptoms between clinic visits. Out of 42 participants, 15 (35.7%) prefer to treat their Zn deficiency through diet, 26 (59.5%) through supplement, and 1 (2.4%) of participants had no preference. Additionally, 35 (85.4%) participants indicated that they were “likely” to comply to a Zn-diet treatment.

Conclusions

CeD patients did not experience improvement in gastrointestinal or extraintestinal symptoms on Zn supplementation. However, a portion of CeD patients prefer to treat and are likely to comply with a Zn diet to treat their deficiency. Based on this knowledge, further studies should investigate the efficacy of a Zn diet compared to supplements CeD patients.

Funding Agencies

CIHR
A182 EXPLORING THE LINK BETWEEN SPECIFIC MICROBIAL STRAINS AND ANXIETY AND DEPRESSION IN PATIENTS WITH ULCERATIVE COLITIS
Authors: Chiew B A , Haskey N , Lewis A , Nadeem H , Gold S L , Taylor L M , McCoy K , Ohland C , McGregor K , Raman M
Published: February 2024

Background

Anxiety and/or depression (A/D) have been identified as significant co-morbidities of ulcerative colitis (UC), and even considered as extraintestinal manifestations, with emerging evidence to support the role for gut microbial dysbiosis in the natural history for both UC and A/D. However, there is a paucity of knowledge regarding the specific attributes of the gut bacteriome in individuals with UC with concomitant A/D.

Aims

To explore the connection between the gut bacteriome and A/D in a cohort of patients with UC.

Methods

This cross-sectional study included 29 participants diagnosed with UC either in remission or with mild to severe disease. To test for depression and anxiety, participants completed the Patient Health Questionnaire-8 (PHQ-8) and General Anxiety Disorder-7 (GAD-7) respectively. Participants provided a stool sample for microbiome analysis and the fecal bacteriome was assessed using metagenomic shotgun sequencing.

Results

Among the 29 patients, 55% were female (n=16) and 45% were male (n=13), 34.5 % (n=10) had a Partial Mayo Score over 5 indicating moderate-severe disease activity (median 3, IQR 1-6). Mean age was 38.3 years (± 12.2 years). Sixty-nine percent were on 5-ASA, 42.9% on steroids, 31.0% on Anti-TNF, and 20.7% on immunomodulators. Mean FCP was 976.4 μg/g (± 1589.2). Forty-four percent (n=12) screened positive for anxiety with a median GAD-7 score of 5.0 (IQR: 1-8), while 26% screened positive for depression with a median PHQ-8 of 3 (IQR: 3-10). Principal Coordinate Analysis (PCoA) reveals distinct clustering between UC patients with or without A/D (Figure 1). Regarding the microbial analyses, the log fold change of Firmicutes bacterium CAG:424, Holdemanella biformis, Blautia hansenii, Bifidobacterium pullorum, Anaerostipes caccae, and Ruminococcus gnavus exhibited positive associations with both A/D, whereas Roseburia sp. CAG:303, Prevotella copri, and Bacteroides stercoris demonstrated negative associations. Uniquely, Faecalicoccus pleomorphus and Lachnospira pectinoschiza showed negative associations only with the PHQ-8.

Conclusions

Our research affirms the presence of anxiety and depression in a cohort of UC patients. The severity of A/D measured by the GAD-7 and PHQ-8 were linked to the levels of specific fecal microbes. We introduce several novel species that warrant further examination in UC patients with and without A/D. As this was an exploratory study, the findings need replication in a larger sample size.

PCoA results reveal distinct bacterial clustering patterns between individuals with minimal anxiety/depression (absence) versus those with mild/moderate/severe anxiety and depression as measured by GAD-7 and PHQ-8.

Funding Agencies

None
A183 SECRETIONS OF LACTIC ACID BACTERIA AS ANTI-HELICOBACTER PYLORI AGENTS
Authors: Creuzenet C , Carroll D , Takougoum J M , mohiuddin m , Auger J , McAlister J , Geddes-McAlister J , Bronner S , Binda S
Published: February 2024

Background

Helicobacter pylori (HP) colonizes chronically 50% of the world population, leading to gastric ulcers or cancers in 2-10 % of infections. Due to rising antibiotic resistance, curtailing HP-induced diseases requires the identification of new anti-HP molecules that can reduce HP viability or virulence. Several studies suggest that oral lactic acid bacteria (LAB) supplementation can enhance HP eradication treatment efficacy, suggesting that some LAB produce bioactive molecules with anti-HP properties. We previously found that 18 LAB secrete molecules with activity against two HP strains. The LAB secretions inhibited HP growth and reduced its urease activity, motility and ability to induce the pro-inflammatory cytokine IL-8 from gastric cells. This is important since gastric inflammation is the hallmark of HP infection.

Aims

We aim to elucidate the mechanism of action involved using 5 LAB strains commercialized by Lallemand Health Solutions, including 2 from their Lacidofil® probiotic formulation. Our goal is to harness the potential of the LAB-secreted molecules as novel alternatives to antibiotics or anti-inflammatory agents to curtail HP-induced gastric disease and concentrated cocktails of LAB secretions may synergize with antibiotics.

Methods

This work uses knockout mutagenesis, exposure assays, RNA-Seq, promoter reporter assays and ELISA.

Results

We showed that signals from LAB secretions are transduced by 2 histidine sensor kinases and RNA-Seq analysis was performed on gastric cells and on LAB-exposed HP in stomach-mimicking conditions to identify the pathways that lead to reduced bacterial virulence and reduced inflammation. Also, the effect of LAB on HP adherence to and invasion of gastric cells was investigated, and LAB-specific transcriptional effects are being investigated via luminescence reporter assays. Finally, using metabolomics and proteomics we identified candidate active molecules, which will be validated using commercial compounds and knockout mutagenesis, along with fractionation of the most active LAB secretions

Conclusions

This work highlights the variability between LAB strains and provides mechanistic insights to explain the benefits of well-characterized probiotics such as Lacidofil® in anti-HP treatment or prophylaxis. Adjuvant LAB secretions could benefit the ~6 million patients who develop gastric ulcers or cancers each year worldwide due to HP infection, also saving billions of annual health care costs.

Funding Agencies

CIHRWestern University and MITACS
A185 A GUT MICROBIOME TRANSITION: THE JOURNEY FROM INDIA TO CANADA
Authors: D'Aloisio L D , Haskey N , Abulizi N , Barnett J , Shetty V , Bhaumik U , Ballal M , Ghosh S , Gibson D
Published: February 2024

Background

Young Indian immigrants and Indo-Canadians face a significantly higher risk of inflammatory bowel disease (IBD) in westernized countries. While the etiology of IBD remains unclear, a gut microbiome that is no longer symbiotic with its host is a key player. However, Indians are underrepresented in microbiome research, therefore we cannot accurately assess the role of their gut microbiome in IBD. To understand why Indians are at a greater risk for IBD in Canada, we must first characterize their gut microbiome.

Aims

This study explores how immigration to Canada impacts the gut microbiome of Indian populations, potentially elevating their risk to IBD.

Methods

Stool samples from healthy volunteers (ages 17-53) were collected from Indians in India, Indo-Immigrants, Indo-Canadians, Euro-Canadians and Euro-Immigrants. DNA was extracted for 16S sequencing on the Illumina MiSeq platform and shotgun sequencing on the Illumina NovaSeq platform. Dietary data was processed in ESHA.

Results

Weighted Unifrac revealed distinct clusters of Indian and Indo-Immigrant samples from the westernized cohorts. The most pronounced difference was between Indian and Euro-Canadians with a pseudo-F value of 49.18 (q = 0.00125). Indian versus Indo-Immigrants resulted in a pseudo-F value of 7.707 (q = 0.00125), and Indian versus Indo-Canadian had a pseudo-F value of 15.95 (q = 0.00125). BugBase estimated a significantly higher stress tolerance in the Indian gut, with Proteobacteria driving this phenotypic prediction. Compared to Euro-Canadians, a significantly higher pathogenic potential was predicted in Indians (pFDR= 1.04e-11) and Indo-Immigrants (pFDR= 1.41e-04), driven mainly from Proteobacteria and Bacteroidetes. Multiple comparisons with LDA revealed Prevotella was over 5 times more abundant in Indians residing in India. The gut microbiome in Indians were also enriched with taxa associated with a plant-based diet. Dietary data showed that 59% of Indians do not consume meat, and they also had the lowest consumption (12% caloric intake) of group 4 ultra-processed food (UPF), whereas the highest consumption of UPF was in Indo-Canadians (61% caloric intake) (pbonf ampersand:003C 0.0001). A frequent trend was observed in Indians living in Canada, which was a reduction in key nutrients including soluble fiber, zinc, iron, and folate, some of which are commonly found in plant-based foods.

Conclusions

Overall findings reveal that a loss of Prevotella abundance was observed in Indo-Immigrants and Indo-Canadians, which was associated with a reduction in key nutrients that are common to a plant-based diet, indicating a transition away from their traditional diet. Their dietary changes may be a driver to the displacement of Prevotella and other taxa commonly found in the Indian gut microbiome.

Funding Agencies

NSERC, Killam