The incidence of esophageal squamous cell carcinoma (ESCC) is very high among the Turkmen population of Iran. Family studies suggest a genetic component to the disease. Turkmen are ethnically homogenous and are well suited for genetic studies. A previous study from China suggested that BRCA2 might play a role in the etiology of ESCC. We screened for mutations in the coding region of the BRCA2 gene in the germline DNA of 197 Turkmen patients with ESCC. A nonsense variant, K3326X, was identified in 9 of 197 cases (4.6%) vs 2 of 254 controls (0.8%) (OR ¼ 6.0, 95% CI ¼ 1.3-28; P ¼ 0.01). This mutation leads to the loss of the C-terminal domain of the BRCA2 protein, a part of the region of interaction with the FANCD2 protein. We observed nine other BRCA2 variants in single cases only, including two deletions, and seven missense mutations. Six of these were judged to be pathogenic. In total, a suspicious deleterious BRCA2 variant was identified in 15 of 197 ESCC cases (7.6%).

Objectives: To determine whether MK801, an NMDA receptor antagonist, blocks glutamate excitotoxicity directly or via other mechanisms such as improving blood supply at the injury site in a rat model of spinal cord injury (SCI). In the present study, the e ects of pre-and posttreatment with MK801 on axonal function, spinal cord blood¯ow (SCBF) and cord water content were studied after acute SCI in rats. Methods: Somatosensory evoked potentials (SSEPs) and cerebellar evoked potentials (CEPs) were used to quantify electrophysiological function, and the hydrogen clearance technique and wet-dry weight measurements were used to measure SCBF and cord water content, respectively. Twenty rats received a 21 g clip compression injury of the cord at T1, and were then randomly and blindly allocated to either MK801 or saline groups. Each rat received an intravenous infusion of drug or saline four times during the experiment (16 min/infusion) with the ®rst infusion (MK801 3 mg/kg) beginning 8 min pre-injury, and the other infusions (MK801 1.5 mg/kg) at 1 h intervals after injury. Control experiments on uninjured rats were performed in 10 rats using the same procedure as above except the clip compression injury of the cord was omitted. Results: In the MK801 groups with or without SCI, the amplitude of the evoked potential peaks, especially the SSEPs, was signi®cantly lower than in the saline group. There were no di erences in SCBF or cord water content between the MK801 and saline groups. Conclusion: Pre-and posttreatment with MK801 inhibits evoked potentials, but does not improve SCBF or cord edema after acute compression SCI in rats. For the ®rst time it has been shown that MK801 produced a blockade of glutamate excitatory transmission in a erent pathways after SCI. Further work is required to determine whether this inhibition is reversible and related to neuroprotection and functional recovery after SCI.

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Background Pancreatic cystic lesions are increasingly identified in persons undergoing abdominal imaging. Serous cystic neoplasms (SCNs) have a very low risk of malignant transformation. Resection of SCNs is not recommended in the absence of related symptoms. The accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) to identify SCNs is not known and may impact clinical care. Aims To evaluate the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) for the diagnosis of SCN. To see how this can impact the decision to resect suspected SCNs. Methods Retrospective cohort study of patients from the University Health Network with suspected SCNs from 2017–2020 who underwent either a CT or MRI of the abdomen. Reports noting pancreatic cystic lesions were identified and reviewed. Only cases with suspected SCNs were included. Clinical (age, sex, symptoms, treatment) and radiographic (type of imaging, reported cyst characteristics) data was collected. Pathology was reviewed for all cases where the cysts was biopsied or resected during follow-up. The gold standard for the diagnosis for SCN was pathology of resected specimen or EUS-guided biopsy cytopathology showing no evidence of a mucinous lesion, CEA level below 10ug per L and amylase level below 50 U/L. Results 163 patients were included in the study. 99 (61%) were female and 98 (60%) underwent CT scan. EUS-guided biopsy was performed in 24 (15%) of patients and 8 (5%) had surgical resection. Multidisciplinary review was performed in 6 of the 8 cases that went to surgery. Of the resected specimens, 5 (63%) were SCN, 1 was a mucinous cystic lesion, 1 was a neuroendocrine tumor and 1 was a carcinoma. Two patients underwent EUS evaluation prior to surgical resection. In one case SCN was resected when EUS reported an undetermined cyst type. Reasons for surgical resection were: the diagnosis of serous cyst was not definitive (n=5), symptoms (n=2), and high-risk mucinous cystic neoplasm identified on EUS (n=1). Of 30 patients with pathology available, 15 (50%) were confirmed to have a SCN. CT and MRI had a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 25%, 52% and 80%, respectively. Conclusions Surgical resection for SCN lesions is driven by diagnostic uncertainty after cross-sectional imaging. Multidisciplinary review and EUS evaluation may improve diagnostic accuracy and should be considered prior to surgical resection of possible SCN lesions. Funding Agencies None

Background Endoscopic submucosal dissection (ESD) has become the established standard for endoscopic removal of large gastrointestinal (GI) lesions and early GI malignancies, with improved outcomes compared to traditional endoscopic techniques and offers an alternative to surgery. However, ESD is technically challenging and requires significant healthcare infrastructure. As such, its adoption in Canada was slow relative to Asia and Europe. Thus far, the practice of ESD has been limited to a small number of tertiary centers. Currently, the availability and practice of ESD across Canada remains unclear. Aims To provide a descriptive overview of the training pathways and practice trends of endoscopists performing ESD in Canada. Methods ESD practitioners across Canada were identified from internal networks and by contacting respective endoscopy units. All endoscopists currently accepting ESD referrals were invited to participate in a cross-sectional survey that was distributed via SurveyMonkey. Results 27 ESD practitioners were identified; current survey response rate was 44% although is expected to increase. Median years of independent ESD practice was 5 (IQR 2.75). All practitioners underwent international ESD training of some type. 92% attended short-term training courses. 50% pursued international ESD fellowship training. 92% received training on animal models. 58% and 33% performed hands-on human upper and lower GI ESD respectively prior to independent practice. In practice, 67% of practitioners noted an increase in number of ESD procedures performed per year from 2015 to 2019. 67% rated the awareness of appropriate ESD indications by referring physicians to be “not so aware” or lower. 75% of practitioners report a patient wait time for ESD of 1–3 months. 67% and 75% rated the difficulty of securing endoscopy time and anesthesia support for ESD respectively to be “difficult” or “very difficult”. 75% were “dissatisfied” or “very dissatisfied” with their institution’s healthcare infrastructure to support ESD. 25% perceived their institution as supportive in expanding the practice of ESD. Conclusions A number of challenges exist for the adoption of ESD in Canada. Training pathways are highly variable, with no set standards and most practitioners pursue international training. In practice, the majority of practitioners express dissatisfaction with their access to necessary infrastructure for performing ESD and feel poorly supported by their centers in expanding its practice. As ESD is becoming the accepted standard in allowing for the minimally invasive treatment of indicated GI lesions; greater collaboration between practitioners, institutions, and healthcare systems is crucial to standardize ESD training and to ensure improved patient access. Funding Agencies None

Background Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the primary method of sampling pancreatic cystic lesions with reported specificity near 100% for diagnosing malignancy. Discrepant positive malignant cytopathology with final surgical pathology of pancreatic cystic lesions has not previously been described. Aims To present a case series and review the literature regarding the implications of positive malignant cytology with discrepant surgical pathology for high risk pancreatic mucinous cystic lesions. Methods Patient demographics, clinical history, procedure details, pathology evaluations and follow-up were collected. A thorough literature review was performed. Results Three patients with high-risk pancreatic cystic lesions on cross-sectional imaging underwent EUS-FNA evaluation. None of these patients had a history of pancreatitis. Cytology was reported as positive for adenocarcinoma in all patients by separate gastrointestinal cytopathologists. All patients underwent surgical resection. The pathology for all resected specimens were reported as intraductal papillary mucinous neoplasm. The resected cysts for two patients demonstrated foci of high-grade dysplasia and the third noted low grade dysplasia. All surgical pathology underwent consensus review by three separate gastrointestinal pathologists. None of the patients were treated with adjuvant chemotherapy. All patients have been followed post-operatively with surveillance magnetic resonance imaging with no evidence of recurrence to date (median follow-up time 239 days, range 133 – 447 days). Conclusions This phenomenon sheds light on the potential for variable interpretations of EUS-FNA cytopathology and surgical resection pathology for high risk pancreatic cystic neoplasms. EUS-FNA may identify foci of adenocarcinoma that is not seen on surgical pathology specimens. Further research is required to examine the long-term outcomes of these patients. Funding Agencies None

Background Endoscopic mucosal resection (EMR) allows for safe and effective removal of large non-pedunculated colon polyps. However, prior studies have shown significant recurrence rates between 10–30% after EMR, which have led to recommendations for close endoscopic follow-up and the use of techniques such as snare tip soft coagulation (STSC) to EMR margins to prevent recurrence. Models such as the Size/Morphology/Site/Access score (SMSA) have been developed to aid in identifying polyp complexity and patients at high risk of recurrence. Numerous individual risk factors for recurrence have previously been reported, however the significance of these factors have varied between studies, with limited data from Canadian centres. Aims To evaluate predictors of recurrence for large non-pedunculated polyps following EMR. Methods Consecutive patients between April 1, 2017 to March 1, 2019 who underwent EMR were retrospectively identified from endoscopy unit administrative records. Patients with non-pedunculated colorectal polyps ≥ 2 cm that were removed by EMR were included if follow-up endoscopy data were available. Polyps found to contain invasive adenocarcinoma on histology and/or were referred for surgical resection were excluded. Patient demographic, pre-procedural, intra-procedural, and post-procedural data to time of first follow-up colonoscopy were extracted. Recurrence was defined as a positive pathology specimen from the EMR scar at follow-up. Adjunctive techniques were defined as the use of any non-snare resection or ablation technique for removal of visible adenoma at the time of the EMR. Chi-square and multivariate regression analyses were conducted for variables of interest. Results 517 patients underwent large polyp EMR during the study time period with 265 patients satisfying inclusion criteria. Median age of patients was 67 years (IQR 14); 48% were female. STSC was performed to EMR margins in 94% of cases. 30.9% and 69.1% of polyps were SMSA grade 3 and grade 4 respectively. Adjunctive removal techniques were utilized in 31% of patients, 95% of which was hot avulsion. 15% of patients had recurrence on follow-up endoscopy. Higher SMSA grade was associated with the use of adjunctive techniques (20% vs. 37%, p=0.006). The use of adjunctive removal techniques (OR 2.92, p=0.007) and male gender (OR 3.45, p=0.002) were the only factors found to be significantly predictive of recurrence on multivariate analysis. Conclusions Male gender and the use of adjunctive removal techniques, particularly hot avulsion, are independently predictive of recurrence after EMR of large complex colorectal polyps. Male patients and those who require hot avulsion may be considered high risk for recurrence and warrant closer follow-up. Funding Agencies None