bluuebunny/crossref_metadata_2025_split huggingface dataset:
A145 UNDERWATER EMR FOR LARGE FLAT DYSPLASTIC COLORECTAL LESIONS IN PATIENTS WITH CHRONIC ULCERATIVE COLITIS
Authors: Yu R , Barclay R 
Published: February 2024

Abstract

Background
Patients with chronic ulcerative colitis are at increased risk of colorectal cancer, in part due to increased prevalence of dysplastic lesions. To reduce CRC risk, endoscopic resection is preferable to surgery if feasible. However, large flat lesions can be challenging to remove endoscopically. We report our experience with underwater EMR for large, flat ulcerative colitis-associated dysplastic lesions.

Aims
To evaluate the safety and efficacy of UEMR for treatment of flat/sessile colorectal lesions with dysplasia, without overt signs of invasive cancer. To analyze rates of complications and outcomes for patients undergoing UEMR and compare to alternative methods of treatment for similar lesions.

Methods
We reviewed our IBD patient database from 2021 to 2023 for ulcerative colitis patients referred for large (≥ 20 mm diameter) flat/sessile colorectal lesions without overt signs of invasive cancer, who subsequently underwent underwater EMR. The procedure was performed by an endoscopist with extensive experience in UEMR for large colorectal lesions.

Results
Eleven de novo lesions in 8 patients (4 female; age 58 ± 14) were successfully treated with single-session UEMR. Mean lesion size was 42 ± 22 mm (range 20 to 80 mm); all morphologically flat (Paris IIa or IIb). Three cases were resected en bloc; the remainder piecemeal. Pathology showed tubulovillous adenoma, N=4 (36%); tubular adenoma, N=5 (45%); traditional serrated adenoma, N=1 (9%); sessile serrated lesion, N=1, (9%); high-grade dysplasia, N=1 (9%). There were no cases of invasive cancer. Endoscopic follow-up available for 5 patients over 10.4 ± 2 months showed benign diminutive recurrent/residual lesions in 2 cases, both amenable to UEMR. There were no procedural complications.

Conclusions
In this series of large, flat dysplastic CUC-associated lesions, UEMR was safe and effective, obviating surgery and endoscopic submucosal dissection.

Funding Agencies
None
A148 OSTEOSARCOMA GASTROINTESTINAL METASTASIS: A RARE ENTITY IN ADULTS
Authors: Alabdulkarim B , Habal F 
Published: February 2024

Abstract

Background
Osteosarcoma is highly aggressive and is the most common primary bone malignancy for both children and adults with a bimodal age distribution. The first peak coincides with pubertal growth spurt and the second is in the seventh and eighth decade of life. They frequently metastasize to the lungs. Metastasis to the gastrointestinal tract is extremely rare and to our knowledge, there have only been 15 cases reported in the literature since 1987, of those only three in the second peak.

Aims
Describe a case of 61-year-old female with periampullary metastatic osteosarcoma. Describe the demographics of osteosarcoma patients who develop gastrointestinal metastasis.

Methods
Search Pubmed using the terms: ("Osteosarcoma"[MeSH Terms] OR "Osteosarcoma"[Title/Abstract]) AND ("Gastrointestinal Tract"[MeSH Terms] OR "Gastrointestinal Tract"[Title/Abstract] AND "Case Reports"[Publication Type]. 113 articles were identified and screened by title. 15 articles were further screened by abstract or full text. 7 articles were identified. the remainder 7 articles were located by screening the references of the previously identified articles.

Results
A 61-year-old woman with a medical history significant for metastatic Osteosarcoma was referred to Gastroenterology clinic July 2023 for anemia investigation. Her Osteosarcoma was first diagnosed in the left femur in 2009. She was known for extensive bilateral lung metastasis, subcutaneous metastatic deposits, and distant bone metastasis. She had undergone over 37 surgeries and multiple sessions of radiotherapy. Aside from neoadjuvant and adjuvant chemotherapy for the primary tumor and the first occurrence of lung metastasis, she refused to undergo further cycles of chemotherapy. She had a 60 mg/dl hemoglobin drop from a previous one in December 2023 and intermittent melena. On gastroscopy, she was found to have a 2 cm bleeding mass in the periampullary area. The pathology report of the biopsies was consistent with metastatic osteosarcoma. It showed fragments of ampullary mucosa incorporating a malignant spindle cell neoplasm with a fascicular growth pattern, including scattered osteoclast-like giant cells, morphologically consistent with the known history of metastatic osteosarcoma.
Of the 15 cases published, 9 were in patients 27 years old and younger, 3 were in patients 50 and older, and 3 were only available as titles. 50% of cases presented with intussusception while the rest had anemia or melena. The site of metastasis was the jejunum in the majority of patients (58%). Other sites included the ileum, stomach, colon, and esophagus. Only one other patient had periampullary metastasis. All patients had lung metastasis.

Conclusions
Gastrointestinal metastasis of osteosarcoma remains a rare occurrence. Our case report describes the second case reported in the literature of periampullary metastasis and the first case reported in older patients

Funding Agencies
None
A152 THE RISK OF UNFAVORABLE HISTOLOGIC FEATURES, LYMPH NODE METASTASIS AND METACHRONOUS ADVANCED NEOPLASIA IN PATIENTS WITH COLORECTAL INTRAMUCOSAL CARCINOMA
Authors: Medawar E , Popescu Crainic I , Djinbachian R , Zarandi-Nowroozi M , Taghiakbari M , Marques P , Kaufman D , von Renteln D 
Published: February 2024

Abstract

Background
Very few studies have described the risk of unfavorable histologic features (UHFs), lymph node involvement (LNI), distant metastasis (DM) and metachronous advanced neoplasia (MAN) after the detection of colorectal intramucosal carcinoma (IMC).

Aims
This study aimed to determine the risk of UHFs, LNI, DM and MAN in patients with IMC, compared to high-grade dysplasia (HGD) or T1 colorectal cancer (CRC).

Methods
A retrospective cohort study was conducted. Through a pathology database search, we identified all consecutive patients with HGD (epithelial) (n=908) or either IMC (lamina propria or muscularis mucosa) or T1 CRC (submucosa) (n=496) diagnosed between 2010 and 2019 at the University of Montreal Hospital Center. We excluded patients with age ampersand:003C40 or ampersand:003E90, IBD, hereditary CRC or post-neoadjuvant therapy. Primary outcome was the risk of UHF, LNI and DM in IMC vs T1. Secondary outcome was the risk of MAN (metachronous advanced adenoma or advanced serrated lesion or CRC) in the IMC group, compared to HGD and T1. Files were reviewed for demographics and index and follow-up findings. The metachronous analysis excluded follow-ups ampersand:003C6 months, no follow-up or previous CRC. Follow-up continued until MAN or last colonoscopy within 10 y. Variables were compared between groups using ANOVA, chi-squared tests or Kruskal-Wallis tests, followed by post-hoc tests. We performed multivariate Cox regressions, adjusting for age, sex, family history of CRC, main lesion location, villous histology, adenomas ≥10 mm, and number of adenomas.

Results
The primary cohort included 90 patients with IMC (mean age 69.4 y., 44.4% female) and 207 with T1 CRC (mean age 69.8 y., 43.5% female), as well as 797 with HGD. The rates of lymphatic invasion, vascular invasion, intermediate differentiation/grade and mucinous histology were 2/90, 1/90, 7/90 and 4/90 in the IMC group compared to respectively 30/207 (2.2% vs 14.5%, pampersand:003C0.01), 15/207 (1.1% vs 7.2%, p=0.06), 68/207 (7.7% vs 32.9%, pampersand:003C0.01) and 15/207 in the T1 group (4.4% vs 7.2%, p=0.52). No other UHFs were present. No patients with IMC had LNI or DM.
In the metachronous outcomes analysis, 464 patients were eligible (mean age 67.1 y., 42.2% female, median follow-up 3.0 y.): 274 with HGD, 58 with IMC and 132 with T1 CRC. Compared to HGD, patients with IMC had a lower likelihood of MAN (HR 0.46, 0.22-0.96), and T1 CRC had a similar likelihood of MAN (HR 0.65, 0.41-1.02). Compared to IMC, T1 CRC had a similar likelihood of MAN (HR 1.39, 0.63-3.09).

Conclusions
Patients with colorectal IMC have a small risk of UHFs, but LNI and DM were not identified in this cohort study and have not been reported. Patients with IMC and T1 CRC do not have an increased risk of MAN compared to patients with HGD.

Funding Agencies
None
A157 ASSOCIATION OF SUBMUCOSAL INVASION WITH THE PARIS CLASSIFICATION OF POLYPS IN THE LOWER GASTROINTESTINAL TRACT
Authors: Scaffidi M , Bechara R 
Published: February 2024

Abstract

Background
Endoscopic evaluation of the colorectum allows for diagnosis of colorectal cancer (CRC) and advanced polyps. In particular, polyps can be described in terms of gross morphology using the Paris classification. Previous work has demonstrated that submucosally invasive (SMI) cancer may correlate with the Paris classification subtypes.

Aims
To determine whether the Paris classification is associated with SMI in a Canadian setting.

Methods
We conducted a retrospective single-centre study using data from 2016 to 2023 of patients with colorectal lesions that were referred for endoscopic submucosal dissection (ESD). Using the Paris classification, we classified polyps as either protruding type (0-I) or flat type (0-IIa, 0-IIb, 0-IIc, 0-III) lesions. Protruding type lesions were further classified as sessile (0-Is), pedunculated (0-Ip) and pseudo-pedunculated (0-Isp) subtypes. Mixed lesions, with two concomitant subtypes, were categorized using the higher classification subtype. We categorized polyps as: protruded lesions, including any mixed lesions with a flat lesion; isolated flat elevated lesions; and flat lesions, both mixed and isolated lesions. We also recorded polyp location, prior endoscopic mucosal resection (EMR), previous biopsy, and polyp diameter (in cm), age, sex, and American Society of Anesthesiology (ASA) class. The primary outcome was SMI as identifed on histopathology. We used logistic regression with backward stepwise entry, Fisher exact test with relative risk (RR) and 95% confidence interval (95% CI), and independent samples t-test. Statistical tests were two-tailed and significant at Pampersand:003C0.05.

Results
In our sample of 130 patients, the mean age was 69.2 years (standard deviation [SD] 10.4), most were male (n=78, 60%), and typically had an ASA score of 3 (n=77, 59.2%). Most polyps occured in the rectum (n=65, 50%) with a mean length was 4.5 cm (SD 2.2 cm). The most common subtype was IIa (n=59, 45.4%). Starting with the covariates of age, sex, ASA, prior EMR, prior biopsy at the same, and length of polyp, the logistic regression model reduced them to three: prior EMR, prior biopsy at the same site, and length. Univariate analysis of these three variables found that there was no significant difference with polyp length and SMI (P=0.147) and no significant association with prior EMR on SMI (RR=0.8 [95% CI 0.3 to 1.9]. The presence of prior biopsies at the same site of the lesions was significantly associated with SMI (RR=2.4 [95% CI 1.2 to 4.7])

Conclusions
We did not find that the Paris classification for type of polyp lesion did not correlate with the presence of submucosal invasion, nor did prior EMR, age, sex, or length of polyp. The presence of a prior biopsy, however, did in fact tend to predict submucosal invasion. Future work should aim to incorporate mortality data and response to treatment into the above analysis.

Funding Agencies
None
A158 DEVELOPMENT OF MODELS TO SUDY THE INTERACTION BETWEEN CANCER STEM CELLS AND THE MICROENVIRONMENT IN COLON CANCER
Authors: Sedeuil M G , Gonneaud A , Giroux V 
Published: February 2024

Abstract

Background
Colon cancer affects 1 in 15 people and is the 3rd deadliest cancer worldwide. The standard of care consists of surgical resection combined with 5-fluorouracil (5-FU) chemotherapy. However, relapses remain frequent due to a partial or complete loss of sensitivity to treatment, also known as chemoresistance. Over the last decades, studies have revealed the importance of intratumoral heterogeneity in this phenomenon, and in particular of two components: cancer stem cells (CSCs) and the microenvironment. CSCs are cells with a high capacity of self-renewal, potency (ability to give rise to different cell types) and resistance to anti-cancer treatments. The microenvironment, for its part, comprises all the components surrounding tumour cells, such as cancer-associated fibroblasts (CAFs). Although their respective importance in resistance has been well studied, it is important to better understand their respective modulation during resistance as well as their interactions.

Aims
Identify the specific changes occurring in CSCs and CAFs, as well as their interactions, during the induction of 5-FU resistance in colon cancer.

Methods
To achieve this goal, we are establishing 5-FU resistant models using organoid lines from colon cancer patients. First, we validated that parental organoids maintain their expected cellular heterogeneity by immunofluorescence. We also confirmed that our parental organoids are sensitive to 5-FU by measuring the survival through a WST1 assay.

Results
Indeed, we showed the presence of CSCs (ALDH1+) and proliferative cells (Ki67+), among others. With a baseline IC50 of 5µM, we concluded that they can be used to generate a 5-FU resistant line. In addition, our initial findings suggest that the conditioned media of CAF cultures decreases the sensitivity of parental organoids to 5-FU, emphasizing the need to study deeper the interaction between these two tumor components

Conclusions
In summary, our preliminary results suggest that the interaction between tumor cells and CAFs modulates the response to chemotherapy. We are currently exploring whether CSCs are particularly involved in this phenomenon. In addition, we are developing patient-derived xenograft models (PDX) sensitive or resistant to 5-FU in order to study in vivo the interactions between CAFs and CSCs. At the end, this project will provide a better understanding of the changes required for resistance, paving the way for new targeted therapies

Funding Agencies
Canada foundation for innovation, Canada Research Chairs
A159 MALIGNANT PERITONEAL MESOTHELIOMA: A CASE OF MISTAKEN IDENTITY
Authors: Seeraj A A , Cheung A 
Published: February 2024

Abstract

Background
In the Western hemisphere, cirrhosis is the most common cause of ascites. One of the least common causes is malignant peritoneal mesothelioma (MPM), which occurs in one in one million cases. MPM can be a diagnostic challenge due to its rarity and features that mimic other causes of ascites.

Aims
To describe a complex case of MPM, highlighting the diagnostic dilemma stemming from the subtleties of presentation, confounders in ascites diagnostic criteria, and indeterminate testing.

Methods
We performed a detailed retrospective chart review of a patient who presented with ascites. He was initially given the diagnosis of decompensated cirrhosis and eventually was diagnosed with MPM. He provided his consent for this case report.

Results
A 37-year-old male presented with progressive ascites and peripheral edema. He had no known exposure to asbestos and consumed 6 standard drinks a day for 2 years; with a prior history of 10 standard drinks a week for over 3 years. His physical examination was unremarkable for cardiac, renal or liver disease. His transthoracic echocardiogram and urinalysis were normal. Abdominal ultrasound showed features of liver cirrhosis with large-volume ascites and a FIB-4 score of 0.34, excluding advanced fibrosis Laboratory investigations including liver tests were normal; with a platelet count of 568 x 109/L. Viral, metabolic and autoimmune liver disease were excluded. A diagnostic paracentesis demonstrated a serum albumin-ascites gradient (SAAG) of 1.3 g/dL. Due to his history of alcohol misuse, imaging findings and high SAAG, he was diagnosed with alcohol-related cirrhosis.
His repeat abdominal ultrasound showed multiple liver nodules. Magnetic resonance imaging was done to investigate for hepatocellular carcinoma; revealing diffuse peritoneal carcinomatosis, cirrhosis and large-volume ascites. Investigations to identify the primary malignancy included a computed tomography chest, colonoscopy and EGD. His EGD was the only positive test; showing a 2cm submucosal gastric lesion with normal gastric mucosa pathology. An endoscopic ultrasound (EUS) with fine needle aspiration was then performed; the lesion appearance in keeping with a gastrointestinal stromal tumor (GIST). Pathology favored a diagnosis of poorly differentiated gastric carcinoma. Cytology was positive for malignancy, with the differential being mesothelioma or adenocarcinoma and a repeat SAAG was 1.0 g/dL. Given the discordances, an ultrasound-guided core biopsy was performed of the peritoneal lesions. Pathology revealed features of poorly differentiated epithelioid mesothelioma. A subsequent review of his gastric biopsies revealed similar cells in retrospect were in keeping with mesothelioma.

Conclusions
The presentation of MPM is not easily distinguishable from other causes of ascites. There must be a high degree of suspicion for malignant ascites in the face of inconsistent clinical and diagnostic findings.

Funding Agencies
None
A162 DEFINING INNATE IMMUNE CELL MECHANISMS UPON HELICOBACTER PYLORI MEDIATED TUMORIGENESIS
Authors: Supreme T , Kim T 
Published: February 2024

Abstract

Aims
Hypothesis: H. pylori interacts with eosinophils to inhibit degranulation, alter eosinophil gene expression and promote gastric tumorigenesis
Aim 1: Elucidate the mechanisms underlying the interactions between eosinophils and H. pylori.
Aim 2: Determine the role of eosinophils during H. pylori mediated gastric tumorigenesis.

Methods
Histological and immunofluorescent staining. Hemotoxilin and eosin staining is important to analyze gastric gland structure and parietal cell loss. Immunofluorescent staining is used to detect and localize specific antigens present in cells and cell membranes.
Gastric organoids: Gastric organoids are an important tool for modelling dissease. Gastric organoids generated from adult stem cells from gastric glands depend on growth factors that mimic tissue regeneration.
Bone marrow derived eosinophils: Bone marrow progenitor cells isolated from murine femur and tibia are easily converted into maturer eosinophils with the addition of cytokine interleukin-5.

Results
Addition of mouse derived eosinophils to gastric organoids significantly increases number of organoids.
To understand the relationship between eosinophils and gastric epithelial cell (GEC) growth, I designed a co-culture experiment that involved incubating mature eosinophils with gastric glands in an extracellular matrix. These findings revealed a significant increase in the number of gastric organoids per well when eosinophils were present compared to the gastric organoids without eosinophils. This observation supports the hypothesis that eosinophils may play a crucial role in promoting gastric tumorigenesis.
Exposure of mouse derived eosinophils to H. pylori significantly increases gastric organoid proliferation.
To explore the impact of stimulating eosinophils prior to incubation with GECs I incubated the eosinophils with H. pylori. As expected, there was a significant increase in the number of organoids per well with the addition of uninfected eosinophils. Interestingly, when H. pylori incubated eosinophils were added to the gastric glands, there was a significant increase in the number of gastric organoids per well compared to uninfected eosinophils.

Conclusions
My preliminary findings have indicated that eosinophils can promote gastric epithelial stem cell proliferation. These results led me to ask how treatment of eosinophils with H. pylori subsequently impacts gastric organoid growth and gastric stem cell proliferation. Interestingly, I found H. pylori treated eosinophils increase growth and gastric stem cell proliferation. These results support my hypothesis as increased proliferation is considered a hallmark of tumorigenesis. There little known about resident and inflammatory GI eosinophils and the role of eosinophils during tumorigenesis in unknown. A better understanding of the role eosinophils play can uncover novel mechanisms to be targeted for therapeutic intervention.

Funding Agencies
CIHR
A164 OPTIMIZING A PROVINCIAL SCREENING PROGRAM FOR DETECTION OF LYNCH SYNDROME
Authors: Winter R , Liu Y , Stone J , Rothenmund H , Chodirker B , Kim C , Klein J , Singh H 
Published: February 2024

Abstract

Background
Up to 30% of those with colorectal cancer (CRC) have an affected family member. Lynch syndrome (LS) is the most common inherited condition predisposing patients to CRC. LS is an autosomal dominant condition associated with microsatellite instability (MSI) and mutations in DNA mismatch repair (MMR) genes, and screening CRC cases ≤ age 70 can identify LS in a cost-effective manner. Manitoba launched Canada's first provincial reflex screening program for all CRC cases diagnosed ≤ age 70 using MMR immunohistochemistry (MMR-IHC) in 2017. Our prior 2022 study evaluating the program showed compliance rates of 89.4% for MMR-IHC reflex testing and a 75.8% overall referral rate of screen-positive cases to genetics. However, only 50% were referred directly by pathologists. Several modifications have since been implemented to enhance the program. These included providing feedback to pathologists, creating an “additional testing comment section” on synoptic pathology reports, and regular review of the pathology reports by a pathology assistant. Information materials were developed to encourage genetic testing among relatives.

Aims
Assess whether modifications to Manitoba’s universal screening protocol improved LS patient outcomes and determine any remaining factors to optimize. We specifically aimed to identify current compliance rates for MMR-IHC testing, the overall referral rate of screen-positive cases to genetics, uptake of genetic referrals and genetic testing as well as rate of cascade testing among relatives.

Methods
Data has been obtained by searching the provincial pathology database for “adenocarcinoma” in the colorectal specimen pathology reports. All specimens from 2022 and Q1/Q2 of 2023 were reviewed, meeting the criteria of: a) specimen from colon biopsy/excision containing the term “adenocarcinoma”, b) patient age ≤70 years, and c) missing MMR centralized by the IT/Pathology department.
Additionally, a random sample of cases categorized as “MMR performed” will be audited. We are in the process of reviewing genetic referrals, genetic uptake and the frequency of reminders triggered to each pathologist.

Results
Currently, a total of 1,308 colonic adenocarcinoma specimens (811 from 2022, 497 for 2023) have been reviewed. Appropriate MMR testing was missed in only 1.5% of cases (13/811 =1.6% missed in 2022, 7/497= 1.4% missed in 2023).

Conclusions
Current MMR testing rates for colonic adenocarcinoma specimens within the Manitoba LS screening program have reached a current compliance rate of 98.5%, a substantial improvement from the prior audit (89.4% previously). Further data collection and analysis is ongoing and will also be presented. The reported rates of compliance are the highest that have been reported from any jurisdiction. This study highlights the sustained efforts required to improve detection of LS.

Funding Agencies
None