bluuebunny/crossref_metadata_2025_split huggingface dataset:
A120 METHYLGLYOXAL (MGO) AS A SUBSTRATE FOR LACTYLATION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Hamilton M , Douchin J , Fréchette M , Giroux V 
Published: February 2025

Abstract

Background
Esophageal squamous cell carcinoma (ESCC) is deadly with a 5-year survival rate of only 15%. With frequent relapse observed in patients, it is known that exposure to treatment can select for certain types of cells known as cancer stem cells (CSC). Considering that, our laboratory established ESCC cell lines with prolonged exposure to anticancer treatments (radiotherapy, 5-FU chemotherapy and combined therapy). As expected, long-term anticancer treatments result in an increase in CSC proportion. Moreover, metabolic alterations were observed, such as enhanced intracellular lactate concentration. Since 2019, lactate has been linked to a new post-translational modification (PTM) called lactylation. This PTM can affect protein-protein interaction or gene expression regulation but little is known about lactylation in ESCC. In addition to lactate, methylglyoxal (MGO), mainly produced through glycolysis, can also be used as a substrate for this type of modification.

Aims
Investigate the role of lactylation in ESCC.

Methods
Three ESCC cell lines (TE11, TE5 and HCE4), an immortalized normal esophageal cell line (STR) and esophageal organoids derived from a chemically-induced ESCC mouse model were used. Cells were treated with lactate or MGO to increase lactylation. Lactylome was determined by mass spectrometry of peptides pulled down using L-lactyllysine (KLA) beads. Western blot (WB) and immunofluorescence (IF) were also performed with KLA specific antibodies.

Results
ESCC and normal cell lines are more sensitive to MGO than lactate to induce lactylation. Interestingly, when compared to normal samples, tumor organoids and ESCC cell lines show increased Glo1 and LDHA expression, 2 conversion enzymes important to produce lactylation substrates. Lactylome analysis of TE11 cells treated or not with MGO showed an increase in several lactylated proteins such as ACTB and CTNNA1. Treatment with MGO also modulated enrichment in biological processes, shifting from hits related to chromatin assembly and mRNA regulation to metabolic processes such as RNA, peptides and glycolytic metabolic processes. Interestingly, the predicted localization of proteins was more cytosolic in MGO-treated cells vs untreated, which was more nuclear. IF with a KLA antibody confirmed those predictions. Finally, lactylation can occur on multiple lysines of proteins. For example, lactylation could be detected on 21 and 16 lysines for NCL or HISTH1B, respectively. Interestingly, lactylation could be detected up to 5 times on the same peptides, for example on CHD5 and CNGA1, which could severely affect the function of that protein domain.

Conclusions
Our results showed that esophageal cells are sensitive to MGO as a substrate of lactylation and that MGO can induce the lactylation of proteins located in the cytoplasm, hence the difference in localization and associated biological processes.

Funding Agencies
CAGCIHR, TRIANGLE, Chaires de recherche du Canada, CRCHUS, Université de Sherbrooke
A125 DOES AI INFLUENCE ADENOMA DETECTION RATES IN FIT-POSITIVE PATIENTS
Authors: McGrath B S , Borgaonkar M , McGrath G S 
Published: February 2025

Abstract

Background
The Fecal Immunochemical Test (FIT) is a screening tool that identifies patients more likely to harbor adenomas or colorectal cancer (CRC). Rates of adenoma detection during colonoscopy can vary significantly among endoscopists. Artificial Intelligence (AI) has been shown to improve adenoma detection during colonoscopy.

Aims
To assess if AI assistance during colonoscopy can improve adenoma detection in FIT-positive patients.

Methods
In October and November of 2023, AI was utilized during colonoscopy for FIT-positive patients at Eastern Health, Newfoundland. The 61 FIT-positive patients who had colonoscopy with AI assistance were compared to 61 FIT-positive age, gender, and endoscopist-matched controls who had colonoscopies performed without AI assistance during the preceding 6 months. Demographic data were collected on all patients as well as colonoscopy findings, including CRC detection, polyp detection, and histology. The primary outcome was the proportion of patients with adenomas in the two groups. Secondary outcomes included advanced adenoma detection rate and sessile serrated lesion detection rate. Sample size was one of convenience as only 61 FIT-positive patients had colonoscopies with AI assistance while AI was temporarily available at our institution. Data were entered in SPSS version 17 for analysis. A chi-squared test was used to compare proportions. The study received approval from the local Health Research Ethics Board.

Results
122 colonoscopies performed by 13 endoscopists (7 General Surgeons, 6 Gastroenterologists) were included. Sixty-eight patients (55.7%) were female and fifty-four patients (44.3%) were male with an average age of 64 (SD = 6.729). Of the patients who underwent AI-assisted colonoscopies, 73.8% had adenomas. Of the patients who underwent colonoscopy without AI assistance, 63.9% had adenomas. There was a non-significant trend toward higher adenoma detection in the patients who had a colonoscopy with AI (x^2=5.165, p=0.076). AI-assisted colonoscopies found advanced adenomas in 44.3% of patients compared to 29.5% in the no AI group (x^2=3,020, p=0.221). In the AI group, 8.2% of patients had sessile serrated lesions (SSL), compared to 1.6% in the standard procedure group (x^2=2.805, p=0.094).

Conclusions
This study showed a trend toward higher adenoma, advanced adenoma, and SSL detection with AI assistance in FIT-positive patients. Repeating this study with a larger sample size might clarify the effect of AI assistance during colonoscopy in FIT-positive patients

Funding Agencies
None
A126 SIGNET-RING CELL CARCINOMA OF THE GALLBLADDER: A CASE REPORT OF UNIQUE BRAIN METASTASIS.
Authors: Alfaraj Z , Grin A , Rai M 
Published: February 2025

Abstract

Background
Signet-ring cell carcinoma (SRCC) is a rare and aggressive subtype of gallbladder adenocarcinoma, representing 1-3% of all gallbladder cancer cases. Diagnosis is established through histopathological examination, which reveals mucin-filled cells that push the nucleus to the periphery. This characteristic contributes to its aggressive nature, leading to local invasion and distant metastases. Diagnosis can be challenging due to its insidious onset, being detected incidentally after cholecystectomy for conditions, such as cholecystitis or cholelithiasis, or after only metastatic symptoms arise. While the most common metastatic sites are abdominal organs, this report presents a unique case of significant brain metastasis, underscoring its aggressiveness.

Aims
To describe a patient with poorly cohesive SRCC of the gallbladder, which exhibited exceptionally rare brain metastasis.

Methods
Case report and literature review.

Results
A 46-year-old male with no significant medical or surgical history presented with abdominal pain and jaundice lasting one week. An MRCP revealed a large gallbladder mass with multiple liver metastasis. Endoscopic ultrasound confirmed the gallbladder mass, and a fine needle biopsy established the diagnosis of poorly cohesive signet-ring cell carcinoma [Figure 1]. Staging images revealed multiple metastatic large brain lesions with mass effect, confirmed by MRI. A multidisciplinary team, including gastroenterology, medical oncology, and radiation oncology, developed a management plan. Due to the poor prognosis linked to brain metastases, the approach included palliative chemotherapy with cisplatin, gemcitabine, and durvalumab, alongside palliative radiotherapy to the brain and a tapering course of dexamethasone. Following the first cycle of chemotherapy, the patient reported significant relief from abdominal pain.

Conclusions
Treatment of SRCC of the gallbladder has not been well studied due to its rarity. For cases without metastasis, a combination of cholecystectomy and chemotherapy may enhance patient outcomes, though the roles of radiotherapy and immunotherapy remain unclear. Unfortunately, many patients present at advanced stages with metastasis, leading to a poor prognosis. This underscores the necessity for further research to identify risk factors and improve early detection. Additionally, more studies are needed to clarify diagnostic and therapeutic approaches to optimize treatment and improve patient outcomes.

Funding Agencies
None
A130 EVALUATING PLACEBO RATES IN EOSINOPHILIC ESOPHAGITIS RANDOMIZED CONTROLLED TRIALS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Ahmed N S , Rivas A , Yuan Y , Qasim A , O’Gorman D , Feagan B , Jairath V , Bredenoord A , Dellon E S , Ma C 
Published: February 2025

Abstract

Background
Eosinophilic esophagitis (EoE) is a chronic inflammatory and progressive fibrotic condition of the esophagus. There are limited treatment options for EoE and a substantial unmet need for effective and safe medical therapies. Drug development in EoE has been hampered by heterogeneous placebo response rates and uncertainty regarding appropriate endpoint configurations. Accurate characterization of placebo response in EoE randomized controlled trials (RCTs) will help inform more future efficient trial designs.

Aims
To conduct a systematic review and meta-analysis to characterize symptomatic, endoscopic, and histologic placebo response rates in placebo controlled EoE RCTs.

Methods
We updated a Cochrane systematic review and meta-analysis, searching MEDLINE, EMBASE, and CENTRAL to January 1, 2024, to identify placebo-controlled RCTs evaluating medical therapies for patients with EoE. Studies were screened independently by 2 reviewers, and full texts were then reviewed for eligibility; all data extracted in parallel. Primary outcome: pooled proportion of clinical, endoscopic, and histologic responders and remitters randomized to placebo, using an intention-to-treat approach and random-effects model. Potential sources of heterogeneity were explored using meta-regression.

Results
A total of 25 RCTs were included. The pooled proportion of clinical response was 40.9% [95% CI: 29.7%-52.8%] with substantial heterogeneity (I2=74.9%). On meta-regression, older age and a higher probability of being randomized to placebo reduced the likelihood of clinical response to placebo. The pooled proportion of histologic remission defined as a peak eosinophil count [PEC] ≤6 eosinophils per high power field [HPF] or ≤1 eos/HPF was 4.3% [95% CI: 2.6%-6.2%] (I2=23.6%) and 1.3% [95% CI: 0.5%-2.5%] (I2=0%), respectively. The mean difference in the EoE Endoscopic Reference score to placebo was -0.56 [95% CI: -0.91, -0.21].

Conclusions
Over 1/3 of patients in EoE trials clinically respond to placebo and this is associated with trial design factors such as randomization ratio and trial population. Objective endoscopic and histologic measures are associated with lower placebo responses. These findings highlight the need to re-evaluate clinical trial endpoint configurations in EoE
Table 1. Pooled proportion of placebo patients achieving response

Abbreviations: CI confidence interval; eos eosinophils; hpf high power field

Figure 3. Association between mean age of trial participants (A) and probability of receiving placebo (B) with proportion of clinical responders to placebo

Funding Agencies
None
A132 PREDICTIVE VALUE OF ENDOSCOPIC EVALUATION IN EOSINOPHILIC ESOPHAGITIS
Authors: Stukalin I , Kota M , Gonsalves N , Gupta M , Ma C 
Published: February 2025

Abstract

Background
Clinical trials for eosinophilic esophagitis (EoE) currently use the peak eosinophil count (PEC) and patient-reported outcomes as coprimary endpoints for determining therapeutic efficacy. Although the PEC reflects histological activity in EoE, it has not been consistently correlated with symptoms nor endoscopic appearance and the prognostic value of endoscopy relative to the PEC is unclear.

Aims
We evaluated the Endoscopic Reference Score for EoE (EREFS) as a predictor of clinically relevant endpoints.

Methods
We evaluated a retrospective prevalent cohort of adults (&gt;18) with EoE undergoing upper endoscopy between 2010 and 2023 from two tertiary care institutions. The EREFS total score, individual components, inflammatory and fibrostenotic subscores were assessed. The primary endpoint was a composite outcome of food bolus impaction (FBI), requirement for esophageal dilation, and hospitalization for EoE within 12 months of the baseline endoscopy. Logistic regression was used to assess the association between EREFS and the composite endpoint.

Results
A total of 350 patients were included (225 [64.3%] male, mean age at presentation 35.0 years [SD 13.6], 299 [85.4%] presenting with predominantly dysphagia). Mean EREFS at baseline was 4.3 (SD 1.8), with a mean inflammatory subscore of 2.3 (SD 1.3) and fibrostenotic subscore of 2.0 (SD 1.0). Most patients had a baseline stricture (269/350, 76.9%) and 135 (38.6%) underwent dilation at baseline to a mean diameter of 14.3 mm (SD 2.4). The mean baseline PEC was 44.3 eos/HPF (SD 35.1). Baseline EREFS was significantly associated with the composite primary outcome (OR 1.32 [95% CI: 1.16, 1.50], p&lt;0.001) whereas the PEC was not associated (OR 1.03 [95% CI: 0.97, 1.10], p=0.30 for each 10 eos/HPF increase). The baseline fibrostenotic EREFS (OR 2.04 [95% CI: 1.58, 2.64], p&lt;0.001) and presence of stricture (OR 6.12 [95% CI: 3.28, 11.43], p&lt;0.001) were significantly associated with the composite primary endpoint, even when patients with baseline dilation were excluded.

Conclusions
The fibrostenotic EREFS subscore is significantly associated with the requirement for future dilation and food bolus impaction, with prognostic value beyond that of the PEC alone.

Funding Agencies
None
A134 TRANSITION FROM PEDIATRIC TO ADULT CARE WITH EOSINOPHILIC ESOPHAGITIS: A PATIENT EXPERIENCE SURVEY
Authors: Hoang T T , Avinashi V , Ko H 
Published: February 2025

Abstract

Background
Healthcare transition for pediatric patients with chronic gastrointestinal diseases is a coordinated process that requires multidisciplinary collaboration to improve an otherwise challenging time for patients and their families. While this process has been explored in other areas such as inflammatory bowel disease, the transition experience has not been well characterized in eosinophilic esophagitis (EoE).

Aims
To better understand and characterize the experiences and attitudes of patients transition from pediatric to adult care with EoE in British Columbia.

Methods
We conducted an online, anonymous, self-administered, 10–15-minute survey of adult patients who had recently transitioned to adult care. EoE patients age ≥ 19 who were discharged from the EoE clinic at BC Children’s Hospital within the past three years and referred to adult gastroenterology at the Digestive Disease’s Centre in Vancouver, British Columbia were invited to participate. The survey included demographics and questions assessing patients’ pre-transition readiness based on a modified Transition Readiness Assessment Questionnaire (TRAQ), and post-transition challenges via a 5-point Likert scale. Free text entries were included to allow for qualitative thematic analysis of patients’ responses.

Results
Of the twenty patients identified who met inclusion criteria, eleven (55%) completed the survey. Only four (36.3%) patients at the time of transition felt prepared to graduate into adult care. While six (54.5%) reported feeling satisfied with the transition process, four (36.3%) felt that the process was more challenging than expected. Seven (63.6%) patients felt that communication between their pediatric and adult physicians was inadequate. Moreover, four (36.3%) patients felt they lost access to non-gastroenterology specialists such as allergists and pediatricians, as well as allied health care members after transition into adult care. Thematic analysis of patients’ free-text responses revealed that disjointed communication between healthcare teams, new therapeutic relationships, and loss of access to medical experts were three concerning themes for transitioning patients. Ten (90.9%) patients agreed a joint clinic between pediatric and adult gastroenterology would have improved their transition experience.

Conclusions
These preliminary data from our ongoing study highlight the challenges associated with EoE pediatric-to-adult transition. Given the identified unifying themes of inadequate communication between care providers, a joint transition EoE clinic between pediatric and adult physicians would be a potential solution to significantly streamline this process.

Figure 1: Patient attitudes regarding (A) pretransition readiness using a modified Transition Readiness Assessment Questionnaire (TRAQ) and (B) post-transition experience.

Funding Agencies
None
A137 A CANADIAN PILOT STUDY: UNSEDATED TRANS-NASAL ENDOSCOPY AND BIOPSIES IN ADOLESCENTS WITH EOSINOPHILIC ESOPHAGITIS WITH VIRTUAL REALITY DISTRACTION
Authors: Avinashi V , Greeley B , Greaney E , Bush J , Jacob J 
Published: February 2025

Abstract

Background
Esoinophilic Esophagitis (EoE) is a chronic condition that requires endoscopy and biopsies for diagnosis and treatment evaluation. In pediatrics, anaesthesiology OR based sedation is standard practice, but it is resource intense, requires full fasting, and involves some risk. Trans-Nasal Endoscopy (TNE) with virtual reality (VR) distraction has successfully been used and evaluated at multiple Children’s Hospitals in the US. It uses thin endoscopes to obtain esophageal biopsies. This service is not available in Canada.

Aims
Demonstrate that unsedated TNE:
- can be done safely in adolescents with EoE
- can be done reasonably comfortably
- tissue samples are adequate for histopathologic evaluation

Methods
A pilot was launched spring 2024 at BC Children’s Hospital offering TNE with VR for EoE patients.
All TNE procedures were evaluated for any complications. Comfort / tolerability, was described using patient surveys including self-reported pain (Faces Pain Scale), worst pain during the procedure; anxiety (Visual Analogue Scale), VR and overall satisfaction from patients, caregivers, and staff. Heart rate was measured throughout. Biopsy samples were reviewed by a pathologist regarding size and quality.

Results
7 teenage males have undergone and completed TNE, without complication. Mean procedure time was 9.6 minutes.
TNE resulted in some pain, which returned to baseline levels (Table 1). Patients’ (range = 5-6), caregivers’ (range = 6-7), and staffs’ (range = 6-7) scores demonstrated satisfaction with the overall procedure. All involved were very likely to recommend VR for the same procedure (range 9-10). All patients reported that they would do TNE with VR again.
Mean HR was elevated from baseline (68 BPM) compared to when the scope was inserted (78 BPM) and stayed elevated (74 BPM).
Mean # of biopsies obtained was 5.7. Average biopsy size in TNE was 0.16 cm (range: 0.1-0.4) compared to the patients’ historical EoE procedures of 0.22 cm (range: 0.1-0.6). One pathologist noted that orientation in one TNE sample was poor, due to small size. Pathologists felt the need to ink the tissues to ensure embedding. No samples were lost. All pathologists found TNE samples were sufficient for evaluation with eosinophil counts reported.

Conclusions
Unsedated TNE with VR distraction at this early junction seems to be safe, reasonably well tolerated, and able to provide adequate specimens. Further research is needed to understand its feasibility in a more diverse sample.

Funding Agencies
Health Innovation Pathway Program: Minstry of Health BC; Equipment by Amacon(R)
A138 EVALUATING THE ACCEPTABILITY AND EFFICACY OF CYTOSPONGE FOR BARRETT’S ESOPHAGUS: A SINGLE CENTRE CROSS-SECTIONAL STUDY
Authors: AlQattan A , Ten-Pow M , T’ien L , Choi M , Chan B , Galorport C , Enns R 
Published: February 2025

Abstract

Background
Barrett’s Esophagus (BE) is a pre-malignant condition defined by the presence of metaplastic columnar epithelial cells above the gastroesophageal junction. Once metaplasia is present, there is a 0.5% annual risk of progression to dysplasia and ultimately adenocarcinoma. Cytosponge is a new device and technique to diagnose BE. Furthermore, this test has a strong safety profile. Research showed increased patient tolerance for the Cytosponge compared to endoscopy; however, this has not been demonstrated in a Canadian setting. Ideally, patient acceptability of Cytosponge device should be evaluated before its integration in a Canadian context.

Aims
To assess patient acceptability, tolerability and integration of Cytosponge in the diagnosis of Barrett’s Esophagus in a Canadian healthcare setting. We also assessed the ease of use and familiarity with Cytosponge.

Methods
A single-centre, prospective cross-sectional study was conducted to evaluate the acceptability and comfort of patients undergoing Cytosponge procedure. Outpatients referred for EGD for Barrett’s Esophagus at St. Paul’s Hospital between 03/21-08/24 were included. 74 patients with BE have been enrolled in this project. Acceptability was evaluated through Visual Analogue Scale (VAS), Spielberger State Trait Anxiety Inventory (STAI), and Impact of Events Scale (IOES) on the day of procedure, day 7, and day 90 post-procedure. Data from health care providers administering the Cytosponge were collected using the System Usability Scale (SUS). One-way ANOVA and Tukey’s Honestly Significant Difference tests were completed to assess score differences between follow-ups.

Results
A total of 74 patients met the inclusion criteria and consented. 89.2% were successful in swallowing Cytosponge, 10.8% were unsuccessful. ANOVA test were statistically significant in VAS scores between day 0 and day 7, day 0 and day 90 with a p-value 0.006 and 0.00005 respectively. Average STAI scores pre- and post-Cytosponge were 41.7 (SD 3.1) and 40.7 (SD 4.4), ANOVA analysis of STAI scores between groups showed no statistical significance. The average IOES score at day 0 was 1.7 (SD 3.4), day 7 1.1, and day 90 0.7. There was no statistically significant difference in IOES scores at follow-up.

Conclusions
Our results demonstrate that Cytosponge is well tolerated in a Canadian healthcare setting. Average STAI and IOES scores were comparable at follow up. Additionally they were not statistically significant suggesting that patients found Cytosponge an acceptable. A score of 68 and above is above average on SUS which measures usability of Cytosponge. The average SUS score in this sample was 55.2 this suggests that there is a learning curve for healthcare providers to become familiar with Cytosponge. There were no complications with Cytosponge in this sample.

Expanded and retrieved Cytosponge device

Funding Agencies
Gastroenterology Institute of Research Institute