bluuebunny/crossref_metadata_2025_split huggingface dataset:
A145 ENDOSCOPICALLY NON-VISIBLE INTERVAL COLONIC ADENOCARCINOMA DESPITE HIGH-QUALITY SURVEILLANCE.
Authors: Vu D C , Busca A , Lee R 
Published: March 2021

Abstract

Background
Colonoscopy remains the gold-standard for screening and surveillance of colorectal cancer (CRC). Regular colonoscopy with polypectomy has been associated with reduced CRC incidence and mortality. However, interval CRC, defined as cancer diagnosed between initial screening and subsequent surveillance colonoscopies, occurs at rates of 2–14%. Identified risk factors for interval cancers include patient-related factors (older age, diverticular disease, proximal CRC), endoscopy-related factors (colonoscopy by non-gastroenterologists or in an outpatient setting; endoscopists with low rates of completion, adenoma detection or polypectomy) and biologic factors (microsatellite instability (MSI), CpG island methylation). We report a patient with interval metastatic ileo-cecal adenocarcinoma despite multiple, high-quality surveillance colonoscopies, not endoscopically visible as no visible intra-luminal mucosal component was present.

Aims
To describe a case of an interval CRC without an endoscopically visible intra-luminal component.

Methods
Case description and literature review.

Results
A 69-year-old male, with a history of multiple advanced colonic polyps requiring multiple surveillance colonoscopies and polypectomies, presented with symptoms of bowel obstruction. An abdominal CT scan revealed findings of terminal ileitis and upstream small bowel obstruction. Colonoscopy was performed, revealing obstruction of the ileo-cecal valve with a firm cecal submucosal lesion without abnormal overlying mucosal abnormalities. Exploratory laparoscopy revealed a mass at the ileo-cecal valve with associated peritoneal deposits. A right hemicolectomy was performed, and pathological examination demonstrated metastatic invasive adenocarcinoma involving the cecum, the terminal ileum and ileo-cecal valve without extension into the lumen or formation of an overt polypoid mass. The tumour extended into the wall of the distal ileum in a circumferential fashion, involving the immediate deep serosa, but with only minimal, focal mucosal ileal involvement and no overt polypoid mass. An independent review of the case and resection specimen by a second pathologist confirmed absence of significant ileal or colonic mucosal involvement and no obstructing intraluminal component.

Conclusions
This case illustrates a rare presentation of an interval CRC that was not identified despite several high-quality surveillance colonoscopies, as only minimal mucosal involvement was present. As endoscopy remains the gold-standard for early detection and removal of pre-malignant lesions and early malignancy, the patient’s presentation with interval malignant bowel obstruction and metastatic disease, despite adequate quality surveillance, demonstrates an inherent limitation of colonoscopy. To our knowledge, this is only the third documented case of endoscopically non-visible interval CRC.

Funding Agencies
NoneNone
A146 EVALUATION OF A COLONOSCOPY REFERRAL FORM IN QUEBEC: WHICH INDICATIONS CARRIES A HIGHER RISK OF ADVANCED NEOPLASIA?
Authors: Chennouf A , Delisle M , Martel M , Ménard C 
Published: March 2021

Abstract

Background
Patients referral for colonoscopy in the province of Quebec are organized through a standardized triage sheet that includes all indications categorized in 5 hierarchal scheduling priorities. In the context of a restricted access to colonoscopy, exacerbated by the COVID-19 pandemic, postponed elective endoscopies lead to potential diagnostic and therapeutic delays in patients with colorectal neoplasia. There is currently an important need to evaluate available tools to improve patients prioritization.

Aims
This study aims to determine CRC and advanced adenomas (AA) rates associated with indications of priority 3 (P3 fig.1). The secondary objective is to regroup and compare indications with higher and lower rate of CRC and AA.

Methods
This retrospective study included all adult patients who underwent a single diagnostic colonoscopy from March 2013 to March 2016 following a single FIT test in a tertiary teaching hospital. A literature review informed the adopted definition of higher-risk of CRC and AA according to P3 colonoscopy indications. These include: Positive FIT test (IN5), hematochezia in ≥ 40 years old patients (IN4), unexplained iron deficiency anemia (IN6) and symptoms suspicious of occult colorectal cancer (IN18). Lower risk P3 indications were defined as: suspicion of IBD (IN3), recent change in bowel habits (IN7), polyp viewed on imaging (IN17), inadequate bowel preparation (IN19), and diverticulitis follow-up (IN20). Higher and lower risk indications findings were analyzed.

Results
In our cohort of 2226 patients, indications for colonoscopy referral according to the standardized form were available for 1806 patients (10 P1, 69 P2, 1056 P3, 56 P4 and 615 P5). In our studied group of P3 indications, the mean age was 62.6±11.3 years, 54.1% were female and 173 (16.4%) patients had a significant finding of CRC or AA (table 1). Patients referred for higher risk indications had a significantly increased rate of CRC and AA (19.3% vs 5.1% p≤ 0.01) compared to patients referred for lower risk indications.

Conclusions
A standardized colonoscopy referral tool may be adapted to improve prioritization of patients at risk of advanced neoplasia. These findings are especially relevant in the context of limited access to colonoscopy like during a pandemic.

Funding Agencies
None
A147 PRIMARY COLONIC MANTLE CELL LYMPHOMA: A RARE ENTITY
Authors: Donaldson K , Nassiri S , Chahal D , Byrne M F 
Published: March 2021

Abstract

Background
Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL), often diagnosed at later stages with secondary gastrointestinal (GI) involvement. Primary GI MCL is rare and is not often discussed in the literature.

Aims
To increase awareness of a rare condition that is likely to be encountered but can be challenging to diagnose.

Methods
Case report and review of the literature.
Results

Case Report
A 78-year-old man with multiple untreated vascular risk factors including atrial fibrillation and type 2 diabetes presented with acute onset left hemiplegia, dysarthria, and imaging consistent with a left pontine stroke. As part of his workup he underwent a CT abdomen/pelvis identifying an 11 x 5 cm intraluminal mass in the transverse colon.
Previous screening colonoscopies, for family history of colon cancer, were notable for tubular adenomas without high-grade dysplasia at 13, 12, 10, 7, and 2 years prior to admission. The patient had 16 pounds of weight loss without other constitutional symptoms, change in bowel habits or evidence of GI bleeding. Bloodwork was notable for microcytic anemia (Hemoglobin 91 g/L, MCV 75 fL), from a normal baseline one year prior, without other cytopenias. C-reactive protein (44 mg/L) and GGT (164 U/L) were elevated. Other liver enzymes, lactate dehydrogenase, and electrolytes were normal.
Colonoscopy revealed numerous polypoid lesions throughout the entire colon and a large non-obstructive mass with submucosal appearance in the transverse colon. Biopsies were taken from the large mass and one of the smaller polypoid lesions. Histology showed a sheet-like infiltrate of small lymphocytes within the lamina propria. Immunohistochemical staining was positive for CD20, BCL2, Cyclin D1, equivocal for CD5, and negative for BCL6 and CD3. Ki67 index approached 30%. A diagnosis of colonic MCL was made.

Literature Review
Primary MCL of the GI tract is rare, accounting for only 1 to 4% of all GI malignancies. There is a male and Caucasian predominance with a median age of 68 years at diagnosis. Presenting complaints may include abdominal pain, anorexia, and GI bleeding. Typical endoscopic features are small nodular or polypoid tumors, between 2mm and 2 cm in size, along one or more segments of the GI tract referred to as multiple lymphomatous polyposis (MLP). A single colonic mass is infrequently seen, highlighting the importance of endoscopy for diagnosis, as subtle findings may be missed on radiographic evaluation. Biopsies for immunohistochemistry are essential to distinguish MCL from other NHLs, as almost all cases express cyclin D1. Despite aggressive immunochemotherapy, prognosis is often poor due to MCL’s rapid progression and early relapse.

Conclusions
Primary GI MCL is a rare entity. Awareness is essential as evaluation and management differ from lymphoma at other sites, and other GI malignancies.

Funding Agencies
None
A148 DESMOID FIBROMATOSIS DIAGNOSED IN A 27-YEAR-OLD MALE AFTER BEING MISTAKEN FOR A GASTRIC GIST
Authors: Albino L G , Guo Y , Dieleman L A 
Published: March 2021

Abstract

Background
The gastrointestinal tract can be affected by both epithelial and non-epithelial tumors. When considering non-epithelial tumors, gastrointestinal stromal tumors (GISTs) are the most common with an incidence of 7–15 cases per million per year. Fibroblastic desmoid tumors, originating from mesenchymal cells, are rarer with an incidence of 2–4 cases per million per year. Despite being distinct lesions, these tumors may appear similar on imaging when they involve the stomach wall or bowel. As a result, they may be confused with one another when initially diagnosed.

Aims
This report aims to present a case where a desmoid tumor was mistaken for a gastric GIST despite extensive investigation prior to laparotomy.

Methods
Retrospective review of one patient.

Results
A 27-year-old gentleman presented with acute left-sided abdominal pain and postprandial fullness that began 2 days prior. A CT-abdomen/pelvis demonstrated a large exophytic mass arising from the lesser sac of the stomach, in keeping with an aggressive gastrointestinal stromal tumor (GIST). He was admitted and was further investigated with an endoscopic ultrasound, which demonstrated an exophytic hemorrhagic mass arising from the muscularis propria of the gastric wall. Again, this was most consistent with a GIST and urgent surgical resection was recommended. An exploratory laparotomy was organized the following day. There were no signs of a GIST intraoperatively, but rather a soft tissue tumor of the left mesentery of the transverse colon. This mass was resected, and a biopsy of the peritoneum was collected. Pathology identified a low-grade spindle cell tumor, CD117/CD34 negative with patchy cytoplasmic and nuclear β-catenin staining, in keeping with desmoid fibromatosis.

Conclusions
This case illustrates how GISTs and desmoid tumors are often mistaken for one another when associated with the stomach wall or bowel. Despite morphologic features of both tumors outlined in the literature, pathology, with focus on specific staining patterns, is necessary in many cases to distinguish the two. This distinction is paramount for appropriate prognostication and management, including timely investigation for associated diseases such as Familial Adenomatous Polyposis in patients with desmoid tumors.

Funding Agencies
None
A149
TRP53 LOSS IN KRT15+ INTESTINAL STEM CELLS SEVERELY AFFECTS SECRETORY CELL FATE AND SELF-RENEWAL
Authors: Dubey A , Gonneaud A , Giroux V 
Published: March 2021

Abstract

Background
Intestinal epithelium homeostasis is maintained by two main populations of stem cells: Lgr5+ and reserve stem cells. Under injury, cell plasticity has been observed in progenitor and differentiated cells. We recently reported that Krt15+ cells are present in small intestinal and colon epithelia, and harbor self-renewal, multipotent and regenerative capacities. As in Lgr5+and reserve stem cells, hyperactivation of Wnt/b-catenin pathway in Krt15+ stem cells lead to tumor formation in the intestinal epithelium. While these intestinal stem cell populations can act as tumor-initiating cells in sporadic colon cancer, little is known about the cell-of-origin of colitis-associated colon cancer (CAC). TP53 alteration is reported as an early event in CAC. Therefore, we hypothesize that Trp53 loss specifically in Krt15+ stem cells will perturb the epithelial homeostasis and lead to tumor formation.

Aims
Identify if Krt15+ cells may act as the cell-of-origin in colitis-associated colorectal cancer

Methods
To induce Trp53 loss specifically in Krt15+ cells, we generated Krt15-CrePR1;Trp53fl/fl (Krt15△Trp53) mice, induced Cre recombination by injecting RU486 (PR agonist) and euthanized the mice at different time points following recombination.
Results

Results
Twelve-month following Cre recombination, adenoma formation was observed in a small proportion of Krt15△Trp53 mice. Though, Trp53 loss in Krt15+ cells severely perturbed the small intestinal morphology in every mouse studied. Increased crypt length and villi width was observed in Krt15△Trp53 vs control mice without any changes in cell proliferation. We also observed an increased number of Tuft cells and goblet cells in the villi of experimental mice. In the crypt, higher number of Paneth cells and aberrant presence of goblet cells were noted in Krt15△Trp53mice. Interestingly, we also observed crypt cells expressing goblet and Paneth cell markers and decreased Notch pathway activation suggesting dysregulation of secretory cell fate. Krt15△Trp53 mice display higher number of fibroblasts in the villi and the submucosa, as well as thickening of the muscularis layer. Interestingly, similar observations (accumulation of secretory cells and fibrosis) have been reported in IBD patients, supporting the possible role of Krt15+ cells in CAC. Furthermore, crypts isolated from Krt15△Trp53 mice rapidly die when seeded as organoids vs crypts from control mice, suggesting that the alterations observed in vivo in Paneth cells might interfere with the stem cell niche and therefore reduce self-renewal of Krt15+ cells.

Conclusions
Trp53 loss specifically in Krt15+ cells impaired cell fate decision, induced secretory cell hyperplasia, affected self-renewal ability, and initiated adenoma formation supporting the possible role of Krt15+ cells in gut inflammation and cancer.

Funding Agencies
Canada Research Chair, Cancer Research Society, CFI
A151 COMPARABLE NEONATAL AND PREGNANCY-RELATED OUTCOMES BETWEEN EARLY AND LATE DISCONTINUATION OF BIOLOGICS IN PREGNANT WOMEN WITH INFLAMMATORY BOWEL DISEASE
Authors: Tao J J , Tandon P , Huang V W 
Published: March 2021

Abstract

Background
Inflammatory bowel disease (IBD) disease activity during pregnancy is related to adverse neonatal and pregnancy-related outcomes. Biologics are used to suppress disease activity, however, since there is known transplacental passage, the American Gastroenterology Association (AGA) recommends timing the final dose with drug-specific half-lives although there is little evidence demonstrating adverse outcomes.

Aims
We aim to assess the safety of early versus late discontinuation of biologics according to drug-specific half-lives by comparing various neonatal and pregnancy-related outcomes.

Methods
This is a REB approved single-center retrospective cohort study on all patients with IBD ≥18 years of age on a biologic agent prior to conception, have a documented final dose during pregnancy, and were seen at Mount Sinai Hospital from 2016–2019. Neonate and pregnancy-related outcomes were compared amongst the two groups (Table 1) using the student’s t-test (birthweight, gestational age, Apgar scores) and Fischer’s exact test (NICU admission, congenital anomalies, GBS, chorioamnionitis) analyzed in SPSS Version 27. The level of significance was set at p&lt;0.05.

Results
We identified 53 patients on biologics pre-conception. 26 patients had a documented final dose (19 early cohort, 7 late cohort) and were included in the analysis. Aside from mean birthweight (3014 vs 3561 g, p=0.036), there were no statistically significant differences between the early and late cohorts for gestational age (37.4 vs 39.0 weeks, p=0.20), 1- and 5-min Apgar scores (7.8 vs 8.8, p=0.37 and 8.5 vs 9.0, p=0.49), NICU admissions (p=0.54), congenital anomalies (p=1.00), GBS (p=0.55), and chorioamnionitis (p=1.00).

Conclusions
Overall, our study suggests that early and late discontinuation of biologics have comparable safety profiles based on various neonatal and pregnancy-related outcomes. In fact, we see significantly higher birthweights in the late cohort along with a consistent (non-statistically significant) trend of later gestational ages, and higher Apgar scores. Further, no cases involving NICU admissions, congenital abnormalities, GBS, or chorioamnionitis were seen in the late cohort. Next, we hope to verify our findings by conducting a prospective cohort study with a larger study population and more comprehensive data collection. This will provide higher statistical power and allow for additional subgroup analyses based on objective disease activity (FCP levels) and therapeutic drug monitoring (serum drug levels).

Funding Agencies
None
A152 INVESTIGATING THE ROLE OF NOVEL NUDT15 VARIANT IN AZATHIOPRINE-RELATED MYELOTOXICITY
Authors: Wang Q , Wilson A 
Published: March 2021

Abstract

Background
Azathioprine (AZA), an immunosuppressant, has classically been used to treat patients with inflammatory bowel disease (IBD). AZA inhibits purine synthesis, and its metabolism occurs via a pathway involving thiopurine methyltransferase (TPMT). While standard TPMT genetic screening is conducted for IBD patients initiating AZA treatment to minimize adverse drug effects (ADE), a majority of patients experiencing ADE have wildtype TPMT. Another gene, NUDT15, has been found to be associated with AZA-related myelotoxicity

Aims
In this study we report two novel variants in NUDT15 and aim to evaluate the impact of NUDT15 variation on its gene expression. We hypothesize that the mutations found within novel NUDT15 variant are detrimental either to the gene’s expression levels or its translation process, resulting in a lower amount of NUDT15 product present and hence translating to AZA-related myelotoxicity observed clinically.

Methods
IBD patients experiencing AZA-related myelotoxicity were recruited for this study. Patients were then genotyped and the NUDT15 variants were replicated through site-directed mutagenesis. The NUDT15 variants were subsequently transformed into mammalian cell lines then E. coli cells. DNA products were isolated, and transcription levels were assessed through RT-PCR.

Results
Patient cohort consisted of 27 AZA-exposed IBD patients who developed myelotoxicity despite their TPMT wildtype genotype. Two novel NUDT15 variants were found. The mutation in one of the variants was placed in 3’ UTR, and hence further research was not pursued. Further analysis was conducted for the variant with mutation in coding region. RT-PCR was conducted to assess and compare gene transcription levels between wildtype and variant NUDT15. Wildtype NUDT15 had a relative gene expression level of 0.8x107, whereas variant NUDT15’s relative gene expression level was at 1.1x107. The two groups were not significantly different in terms of gene expression.

Conclusions
Contrary to our initial hypothesis, it appears that the mutation in the start codon for variant NUDT15 gene does not significantly impact its gene expression as compared to the wildtype gene. We are currently pursuing protein expression analysis studies to assess for translational deficits possibly present in the novel NUDT15 variant.

Funding Agencies
SRTP - Schulich School of Medicine
A154 PROTEOMIC IDENTIFICATION OF INFLAMMATORY AND FIBROSTENOTIC BLOOD SERUM BIOMARKERS IN CROHN’S DISEASE
Authors: Mainoli B , Filyk A K , Lu C , Dufour A 
Published: March 2021

Abstract

Background
Crohn’s disease (CD) is an incurable relapsing-remitting inflammatory bowel disease (IBD) where patients may experience bowel damage with symptoms such as abdominal pain, chronic diarrhea, extraintestinal manifestations and life-long disability. CD is heterogeneous with three distinct phenotypes including a stricturing phenotype marked by intestinal fibrosis. This fibrotic morphology is generally more unresponsive to drug treatment; delaying a patient’s remission, control of the disease and often requiring surgical intervention. Thus, early and accurate identification of fibrostenosis in CD is important to optimize patient treatment and predict response to therapy.

Aims
The aim of our study is to distinguish inflammatory and intestinal fibrostenosis in CD patients using serum protein biomarkers.

Methods
Blood sera from 17 inflammatory and 17 fibrostenotic CD patients were collected. The phenotypic classification was confirmed by intestinal ultrasound and endoscopy. Samples were subjected to Shotgun Proteomics, an unbiased proteomics approach that allows for relative protein quantification. Proteins from each condition were isotopically labelled with formaldehyde (light +28 Da and heavy +34 Da), pooled and digested with trypsin. Following liquid chromatography and tandem mass spectrometry, peptides were then identified by MaxQuant software with a false discovery rate of 1%. Excel (Microsoft), Prism (Graphpad) and Metascape software were used for data filtering and analysis.

Results
Proteomic processing allowed for the identification of novel protein biomarkers in the inflammatory and stricture CD phenotypes. Inflammation was correlated with activation of the complement pathway and fatty acid metabolism; marked by increased levels of immunoglobulin gamma 4 chain (IGHG4), mitochondrial creatinine kinase (CKMT1), apolipoprotein A (LPA) and glutathione peroxidase 3 (GPX3) proteins. Fibrostenosis showed no distinct metabolic pathway, but an elevated expression of SWI/SNF-related matric associated actin (SMARCA5), haptoglobin related protein (HPR), immunoglobulin kappa and immunoglobulin heavy constant proteins.

Conclusions
Our data indicate that inflammation and strictures in CD may be driven by distinct signaling pathways. We identified specific protein signatures for the two phenotypes, which may aid in predicting those who are at risk of developing strictures and in the development of phenotype-specific treatment for CD patients. Future validation of these proteins will be performed to assess this unique protein profile.

Funding Agencies
McCaig Institute for Bone and Joint Health