bluuebunny/crossref_metadata_2025 huggingface dataset:
A133 GASTRIC ESD: PRELIMINARY EXPERIENCE IN A TERTIARY CENTER IN QUEBEC
Authors: Maillet D , Desilets E , Maniere T
Published: March 2021

Background

Endoscopic submucosal dissection (ESD) is an endoscopic procedure developed in Asian countries to treat early gastric cancer (EGC). Western countries have less experience with this challenging technique.

Aims

The goal of this study is to evaluate the effectiveness of ESD as a preliminary experience.

Methods

This is an unicentric retrospective study of all consecutive gastric ESD for adenomas or EGC from 07/2017 to 08/2020. The primary endpoints were en bloc and R0 resection rates.

Results

Nineteen patients (mean age 74.2 (54–88), sex ratio 3F/16M) and 23 lesions were included. Mean diameter was 25 mm (10–90). Treatment was previously performed in 7 cases (30.4%), by ESD (5) or EMR (2). The procedure, performed under general anaesthesia, lasted on average 148 minutes (45–412). En bloc resections were performed in 16 cases (69.6%); 5 cases (21.7%) were converted to P-EMR and there was a failure to resect the lesion because of deep invasion or perforation in 2 cases (8.7%). Pathologic examination demonstrated 2 low-grade dysplasia, 4 high-grade dysplasia and 15 adenocarcinomas: intramucosal (8), sm1 (2), sm2 (2), sm3 (1) or sm deep (2). R0 and curative resection rates were 43.5% and 39.1% respectively. The complication rate related to the procedure was 30.4% including 5 perforations and 2 delayed bleeding: all were managed endoscopically. Five patients (21.7%) underwent subsequent gastrectomy for non-curative resection (4) or failed resection (1); 3 had no residual disease on final pathology, 1 had high grade dysplasia and 1 had intramucosal adenocarcinoma. One patient went to palliative care because he was unfit for surgery. Follow-up endoscopy was completed in all 17 patients who underwent endoscopic resection (mean 10 months (2–24)). Recurrence occurred in 23.5% (4/17); all were successfully treated by another ESD.

Conclusions

In our preliminary experience, the rate of en bloc and R0 resection were 70% and 44%. Compared to other studies, these low en bloc and curative resection rates may be explained by technically difficult lesions during the learning curve and might improve with experience. Nevertheless, surgery has been avoided in 13/19 patients (68%) with endoscopic intervention.

Funding Agencies

None
A140 OUTCOMES OF ENDOSCOPIC ABLATIVE THERAPY AND SURGICAL MANAGEMENT IN BARRETT’S ESOPHAGUS: DEVELOPMENT OF A MULTIDISCIPLINARY DATABASE
Authors: Wilson H A , Blakely P , Sun W , Dang J , Karmali S , Wong C
Published: March 2021

Background

Barrett’s Esophagus (BE) is a precancerous condition in which epithelial cells of the esophagus undergo metaplasia from stratified squamous to simple columnar. This metaplasia predisposes the epithelial cells to a stepwise progression of dysplasia, and ultimately esophageal adenocarcinoma. The risk for developing malignancy increases with greater degrees of dysplasia; therefore, current intervention is focused on reducing the incidence and progression of dysplasia. There is good evidence that endoscopic therapies, such as resection and ablation, are effective at treating dysplasia in BE; however, the optimal modality to reduce recurrence is unclear. While proton pump inhibitors (PPI) remain the mainstay of medical treatment, fundoplication may be indicated for failure of medical therapy and patients with anatomical defects such as hiatal hernias. There is currently a lack of guidelines for optimal combined medical and surgical treatment for patients with BE who have received endoscopic treatment.

Aims

Our aim is to create a novel multidisciplinary database of endoscopically treated patients with BE that will allow us to monitor long-term outcomes and disease progression.

Methods

A systematic review on the impact of fundoplication on the progression of BE to dysphagia and adenocarcinoma is underway. Using an existing database as a foundation, we developed a prospective database of patients with BE using RedCAP, a secure cloud-based database. Feedback from specialists in both Gastroenterology and General Surgery contributed to a database that is to our knowledge, the first to combine medicine and surgery.

Results

As proof of concept, we entered seven participants’ information into the database. The majority of participants had risk factors for BE, including caucasian ethnicity, male gender, age > 50 years, and elevated BMI. Five came from the endoscopic ablation program and two were referred by surgery. Four patients underwent laparoscopic Nissen fundoplication, of which three had concurrent hiatal hernia repairs. Two have been seen for post-surgical surveillance. One remained dysplasia free PPI dose was reduced. The other demonstrated a reduction of BE, but continued the same dose of PPI and is scheduled to receive ablation therapy.

Conclusions

Our preliminary results indicate our database can successfully monitor both medical and surgical parameters of patients with BE. With additional participants and longitudinal data, we are positioned to provide evidence-based guidelines to treat and monitor endoscopically treated patients with BE from both a medical and surgical perspective.

Funding Agencies

None
A156 SERUM TUMOUR NECROSIS FACTOR-α ANTAGONIST DRUG CONCENTRATIONS IN PATIENTS WITH PYODERMA GANGRENOSUM ASSOSCIATED WITH INFLAMMATORY BOWEL DISEASE
Authors: Mikail M , Wilson A
Published: March 2021

Background

The utility of therapeutic drug monitoring for guiding the dosing of tumor necrosis factor-α antagonists (TNFAs) in luminal inflammatory bowel disease (IBD) is well-established and well-accepted. TNFAs, specifically infliximab and adalimumab, have become integral to the management of the rare, neutrophilic dermatosis, pyoderma gangrenosum (PG) in IBD. Little is known regarding the target serum TNFA concentrations to guide dosing to achieve resolution of PG in IBD.

Aims

To describe the serum TNFA concentrations (infliximab or adalimumab) associated with the resolution of PG lesions in patients with IBD.

Methods

Patients with IBD and associated PG treated with one of infliximab or adalimumab (collectively known as TNFAs) seen at two academic hospitals affiliated with Western University were identified. Serum TNFA concentrations were assessed at the time of PG treatment.

Results

Nine patients were identified. All patients had IBD-associated PG. Seven patients were treated with infliximab and 2 patients were treated with adalimumab. All patients received standard dosing. Eight patients had complete resolution of their PG, while one had near complete resolution at the time of last follow-up. A median serum infliximab concentration of 3.00 (IQR, 3.52) µg/ml at week 14 and a median serum adalimumab concentration of 2.02 (IQR, 0.98) µg/ml at week 12 were seen at the time of PG treatment.

Conclusions

Herein, we report low serum TNFA concentrations despite PG healing in a cohort of IBD patients. This is lower than what is in patients for successful TNFA treatment in luminal and fistulising IBD.

Funding Agencies

NoneNone.
A173 INNOVATIVE CARE FOR INFLAMMATORY BOWEL DISEASE PATIENTS DURING THE COVID-19 PANDEMIC: USE OF BEDSIDE INTESTINAL ULTRASOUND TO OPTIMIZE MANAGEMENT
Authors: Novak K L , Ma C , Kheirkhahrahimabadi H , heatherington j , Ingram R , Martin M , Panaccione R , Kaplan G G , Devlin S , Seow C , Chan M , Lu C
Published: March 2021

Background

The COVID-19 pandemic has led to significant alterations in the ability to deliver outpatient care to patients with inflammatory bowel disease (IBD) including endoscopic evaluation. This has highlighted the need for alternative, accurate, non-invasive strategies to safely assess disease activity.

Aims

The aim of this study is to describe the impact of point of care intestinal ultrasound (IUS) in a university-based tertiary care IBD urgent access clinic.

Methods

We prospectively evaluated a comprehensive care pathway which incorporated outpatient sigmoidoscopy and intestinal ultrasound with the purpose of directing further ambulatory clinical care and avoiding hospitalization or hospital-based investigations including endoscopy during the COVID pandemic for patients with established IBD with symptoms suggestive of a disease flare, or those at high risk of a new diagnosis of IBD. Non-invasive markers C Reactive Protein (CRP) and fecal calprotectin (fCal) were collected where available. Patients were pre-screened for influenza-like illness, as COVID-19 testing was not available for this population during the study period. Substantial management changes were defined as addition of any medications, biologic switch/ optimization, and or referral for surgical consultation.

Results

Between March 15th and June 30th 2020, a total of 72 patients were seen in the urgent access clinic. All patients were seen within 7 days of referral. The majority were female 57% (41/72) and/ or had Crohn’s disease 65.5% (47/72) (Table 1). Of these, 84.7% (61/72) underwent a substantial management change based on features of active inflammation detected by either IUS alone (53% 38/72) sigmoidoscopy alone (12.5% 9/72) or combination IUS with in-clinic sigmoidoscopy (32% 23/72) in addition to CRP and fCal. Three new diagnoses of IBD were made: one colonic Crohn’s and 2 with ulcerative colitis. One pregnant patient avoided all acute care utilization. Five patients were referred to colorectal surgery for urgent resection including two patients admitted directly for emergent operations. No patients required visits to the emergency department. Furthermore, there have been no unscheduled hospitalizations occurred in this cohort since inception March 23, 2020 til November 15th 2020.

Conclusions

The implementation of IUS in a centralized, urgent access clinic pathway resulted in efficient and meaningful changes in IBD management while sparing the need for acute care services including ER visits, need for in-hospital endoscopy, and hospitalization. The pandemic highlights the utility of this patient-center tool and supports expansion of wider IUS adoption.

Funding Agencies

None
A184 INCIDENCE OF VENOUS THROMBOTIC EVENTS AND RISK FACTORS IN CHILDREN HOSPITALIZED WITH INFLAMMATORY BOWEL DISEASE: A RETROSPECTIVE, CASE-CONTROL STUDY
Authors: Ding Z , Sherlock M , Zachos M
Published: March 2021

Background

Limited research has been published to describe the incidence of venous thromboembolism (VTE) and relevant risk factors in Canadian children with inflammatory bowel disease (IBD).

Aims

The present study aimed to investigate the incidence of VTE amongst hospitalized pediatric IBD patients over a 10-year period and identify risk factors for the development of VTE.

Methods

A retrospective, matched case-control study was performed at McMaster Children’s Hospital. Hospitalized pediatric patients with IBD (<18 years old) from September 2009 to August 2020 were selected. Inpatient data was extracted from the medical record database, including baseline demographic data, thromboembolic events and potential risk factors for VTE.

Results

There were 890 hospitalizations of IBD patients during the study period. 15 (1.69%) were diagnosed with a VTE, including 4 males and 11 females (mean age 13.4±2.9 years old). 12 ulcerative colitis (UC) (80%) and 3 Crohn’s disease (CD) (20%) hospitalizations were comprised in the VTE group. There was a significant difference in VTE rate between females (2.7%) and males (0.8%) (P = 0.03). The VTE rate in the UC group (4.2%) was significantly higher than in the CD group (0.6%) (P = 0.001). The incidence of VTE amongst hospitalized IBD patients did not vary over the 10-year period (P = 0.496). Length of stay in hospital, albumin level and central venous catheter were shown to be significantly different, although they were not identified as independent risk factors (P >0 .05). Of the 15 hospitalizations with VTE, 6/15 (40%) were superficial VTEs in the extremities and 9/15 (60%) had a deep vein thrombosis (DVT) including 6 in the extremities and 3 in the abdomen. VTEs were associated with a peripheral line in 7 patients and with a PICC line in 4 hospitalizations. 2 of 9 (22%) with extremity DVT developed symptomatic pulmonary embolism. An inherited thrombotic condition was identified in 2 of 15 with VTEs. 12/15 (80%) with VTEs were symptomatic and all VTE related symptoms happened in patients with extremity thrombosis and pulmonary embolism. 7 of 15 (47%) VTEs were treated with anticoagulation therapy for 1–6 months. VTE related symptoms and repeat imaging tests significantly improved, and no patient developed a bleeding complication as a result of treatment.

Conclusions

The VTE rate in pediatric IBD patients was relatively low at McMaster Children’s hospital. Children with VTE were disproportionately females with ulcerative colitis compared with children with no VTE. Central venous line insertion may be correlated with the risk for VTE in children with IBD. Most VTEs and related symptoms happened in patients with extremity thrombosis and secondary pulmonary embolus. Anticoagulation therapy in children with IBD with active disease appears to be safe.

Funding Agencies

Kids Dig Health Funding from McMaster Children’s Hospital, McMaster University
A185 THE IMPACT OF PRIOR SURGERY ON ADVERSE PREGNANCY OUTCOMES IN PREGNANT PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Chis R , Tandon P , Huang V W
Published: March 2021

Background

During the course of inflammatory bowel disease (IBD), approximately 20% of patients with ulcerative colitis (UC) and 80% of Crohn’s disease (CD) patients will require surgery. The most common operation is total proctocolectomy and ileoanal pouch anastomosis (IPAA) for UC patients and ileocecal (IC) resection for CD. In pregnant IBD patients, guidelines name the presence of IPAA as a relative indication for Cesarean section (C-section). The effect of prior IBD-related surgery on mode of delivery and pregnancy-related outcomes remains unknown.

Aims

To describe pregnancy-related outcomes in pregnant women with IBD who have undergone prior IBD-related surgery.

Methods

We performed a retrospective cohort study of pregnant women with IBD including those with prior IBD-related surgeries including IPAA, IC resection, total or partial colectomy and ileostomy formation who delivered an infant at our medical center from 2016 to 2020. We assessed the mode of delivery, delivery characteristics (emergency vs. planned C-section) and maternal and neonatal outcomes

Results

Fifty-six UC patients and 64 CD patients were included in the analysis, of which 10 and 24 had undergone prior IBD-related surgery, respectively. The mean age at conception was 34.10 years in the surgical UC group and 30.30 years in the surgical CD group.

Mode of delivery: C-section rates were higher in post-surgical compared to non-surgical UC patients (70% vs. 30.4%, p = 0.02). Similar numbers of C-sections were performed emergently in the surgical compared to non-surgical UC group (10% vs. 18%, p = 0.53). Comparatively, there was no significant difference in C-section rates in post -surgical compared to non-surgical CD mothers (50% vs. 40%, p = 0.44), with 13% performed emergently in both groups.

Maternal outcomes: Gestational diabetes developed in 10% of surgical UC and 4.5% of surgical CD patients. Premature rupture of membranes developed in 10% of surgical UC and 9.1% of surgical CD patients. There was no difference in pre-eclampsia rates in the surgical and non-surgical CD groups (9.1% vs 13.2%, p = 0.64).

Neonatal outcomes: There was no significant difference in pre-term birth rates in post-surgical compared to non-surgical UC mothers (10% vs. 15.2%, p = 0.67) or in surgical compared to non-surgical CD mothers (13.6% vs. 5.1%, p = 0.29). Neonatal Intensive Care Unit (NICU) requirements were higher in infants born to post-surgical CD compared to non-surgical CD mothers (18.2% vs. 2.7%, p = 0.04). More low birth weight (LBW) infants were born to post-surgical CD vs non-surgical CD mothers (13.6% vs. 0%, p = 0.02).

Conclusions

Women with IBD who have had prior IBD-related surgery may be at increased risk of developing adverse gestational and neonatal outcomes. Women with surgical UC have an increased incidence of Cesarean delivery.

Funding Agencies

None
A195 A RARE CAUSE OF SEVERE REFRACTORY DIARRHEA IN A PATIENT WITH COMMON VARIABLE IMMUNE DEFICIENCY ASSOCIATED INTESTINAL ENTEROPATHY
Authors: Markandey B , Beyak M J , Perez S , Manley P , Ropeleski M
Published: March 2021

Background

CVID is the most common type of severe antibody deficiency. Gastrointestinal manifestations affect approximately 20–50% of patients. Boland et al. described in a case series that 2/3 CVID patients were able to achieve clinical and endoscopic remission with Vedolizumab. This α4β7 integrin antagonist inhibits intestinal T cell translocation by blocking integrin interactions with mucosal vascular addressin cell adhesion molecule 1, reducing lymphocyte mediated inflammation. However, despite its novel use for this indication, limited data is available on the consequences of this therapy in patients with CVID.

Aims

To report on a case assessing the efficacy and outcomes of Vedolizumab for the treatment of CVID associated autoimmune enteropathy.

Methods

We present the case of a 50-year-old male presenting with severe refractory diarrhea and malnutrition. A colonoscopy demonstrated patchy ulceration and biopsies revealed ulcerated active colitis, negative for CMV. He was treated with Vedolizumab and Total Parental Nutrition (TPN). His diarrhea resolved, he gained 20 kg and he was weaned off TPN. In 2019, he re-presented with severe diarrhea. Subsequently endoscopic evaluation revealed patchy edematous colonic mucosa and biopsies demonstrated minimally active colitis, negative for CMV. He again responded to Vedolizumab re-induction, however shortly after, his diarrhea returned aggressively. CT enterography demonstrated active jejunal inflammation. Subsequently, an EGD revealed multiple duodenal ulcers and luminal narrowing. Biopsies of the small bowel were sent to histopathology.

Results

CMV superinfection was diagnosed on pathology (image 1). This patient’s diarrhea completely resolved with IV Gancyclovir and he was discharged on maintenance treatment with oral Valganciclovir.

Conclusions

This represents the first reported case of CMV enteritis secondary to Vedolizumab for the treatment of CVID associated autoimmune enteropathy. In this case, clinical and endoscopic remission was observed with Vedolizumab, however subsequently hampered by CMV reactivation. Hommel et al., published a positive correlation in a single centre retrospective cohort study of CMV reactivation in patients with ulcerative colitis treated with Vedolizumab. A large retrospective review of data from a multicenter consortium database of over 1000 Vedolizumab treated IBD patients reported CMV colitis in only 4 patients. CMV reactivation appears to be an exceptionally rare but important event in patients treated with Vedolizumab. Based on this report, patients with CVID associated enteropathy and refractory diarrhea should be carefully screened for CMV when treated with Vedolizumab. Further prospective data assessing the incidence of CMV reactivation in patients with Vedolizumab therapy is required to further define these findings.

Funding Agencies

None
A196 MORE MICROSCOPIC THAN WAS THOUGHT: A RARE CASE OF ISOLATED LYMPHOCYTIC ILEITIS WITHOUT MICROSCOPIC COLITIS
Authors: Singh K S , Yanofsky R , Haegert D , Gao Z , Bessissow T
Published: March 2021

Background

Microscopic colitis (MC) is a chronic inflammatory disease of the colon characterized by lymphocytic infiltration with (collagenous colitis) or without (lymphocytic colitis) the expansion of collagen fibres, and the normal macroscopic appearance of the mucosa on ileocolonoscopy. Recent studies have shown that the ileum may be involved in MC, occurring concurrently with colonic disease, however there is sparse literature on isolated lymphocytic ileitis without colitis.

Aims

We describe the case of isolated small bowel lymphocytosis without evidence of lymphocytic colitis to highlight the utility of random biopsies of the terminal ileum in cases where microscopic colitis is a diagnostic consideration.

Methods

A 70-year-old female known for cutaneous mastocytosis presented with six weeks of abdominal pain, non-bloody diarrhea, intolerance to oral intake and significant weight loss. Computed-tomography showed evidence of possible mesenteric panniculitis. Colonoscopy revealed a normal colon and normal-appearing mucosa of the terminal ileum. Random mucosal biopsies were taken to assess for microscopic colitis, with terminal ileal biopsies revealing significant lymphocytic infiltration consistent with lymphocytic ileitis. Biopsies throughout the colon revealed normal colonic mucosa without evidence of concurrent microscopic colitis. Gastroscopy was macroscopically unremarkable and random biopsies in the stomach and duodenum were negative for Helicobacter pylori and lymphocytosis. Immunostaining of the gastric, duodenal, terminal ileal and colonic biopsy specimens were negative for CD25, CD117 and tryptase, indicating the absence of gastrointestinal mastocytosis.

Results

The patient was diagnosed with lymphocytic ileitis and given the known response of MC to budesonide, she was treated with eight weeks of budesonide with clinical improvement leading to remission of her symptoms.

Conclusions

This case illustrates a rare incidence of isolated ileal microscopic ileitis without colitis that responded well to standard MC treatment, thereby underscoring the utility of random biopsies in the terminal ileum and throughout the colon when microscopic colitis is on the differential diagnosis.

Funding Agencies

None
A201 UNDERSTANDING THE INFECTION DYNAMICS OF MYCOBACTERIUM PARATUBERCULOSIS (MAP)
Authors: Baruta G M , Zhang H , Alston L , Hirota S A
Published: March 2021

Background

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease (JD) in ruminants. Following infection, JD may present as enteritis, leading to wasting, often causing premature culling of livestock. Beyond veterinary medicine, several mycobacterium species, including MAP, have been implicated in human gastrointestinal disease. While MAP has been incriminated in causing Crohn’s disease (a claim that has yet to be substantiated), there are confirmed cases of MAP infection in immunocompromised individuals, causing profuse diarrhea, fever, and drastic weight loss. Given the economic burden associated with MAP infection, considerable efforts have sought to understand its dynamics. However, these processes have not been completely characterized, hindering our ability to generate novel anti-infective agents. While the current paradigm suggests that MAP travels to the small intestine, gaining entry through the epithelium, the exact cellular tropism and the mechanism(s) of entry are not well defined. Therefore, we have developed an ex vivo enteroid-based system to visualize invasion of MAP in distinct cells of the intestinal epithelium using a GFP-expressing MAP strain. With this, we sought to test the hypothesis that MAP invasion occurs via M cells through receptor-mediated transcytosis.

Aims

1) Characterize experimental system and visualize MAP invasion 2) Determine cellular tropism 3) Uncover mechanisms underlying MAP invasion

Methods

Enteroids (2D and 3D) were generated and M cell differentiation induced via addition of RANKL. Confluent ileal monolayers were exposed to GFP-expressing MAP strain (K10 pWES4). Confocal microscopy was performed, and barrier function was measured via transepithelial electrical resistance (TEER).

Results

We generated 3D enteroids and confluent enteroid-derived monolayers with functional M cells capable of transcytosis. MAP was detected mainly within M cells. We further confirmed this finding using a human in vitro M cell model, the Caco-2/Raji-B co-culture system. Furthermore, alterations in TEER following MAP exposure in monolayers cultured with RANKL, triggering M cell differentiation, suggest the existence of a novel mechanism by which MAP disrupts the barrier to invade the mucosa.

Conclusions

Our results suggest that MAP translocates across the epithelium predominantly via M cells, as shown both in a human and murine model. This newly optimized approach provides an experimental system that will enable us to better characterize M cell-MAP interactions, with the hopes of identifying new therapeutic targets to prevent the spread of MAP and reduce economic impact of JD. Beyond MAP infection, this novel ex vivo system has potential to elucidate other host-pathogen interactions.

Funding Agencies

Natural Sciences and Engineering Research Council of Canada (NSERC)
A211 SPONTANEOUS HBV REMISSION AFTER HBV REACTIVATION FOLLOWING TREATMENT WITH SOFOSBUVIR AND VELPATASVIR IN A PATIENT WITH HCV AND HBV CO-INFECTION: CASE REPORT
Authors: Chiang A , Tsoi K
Published: March 2021

Background

In co-infected patients with hepatitis B (HBV) and hepatitis C (HCV), the treatment of HCV with direct-acting antiviral agents (DAA) can cause HBV reactivation. However, there are no clear guidelines on the timing of treatment initiation, especially in the absence of clinical signs of flare.

Aims

Here we discuss the case of a 34-year-old female with HBV and HCV genotype 3 who had HBV reactivation following HCV treatment, but did not require nucleos(t)ide therapy.

Methods

She initially presented with chronic inactive hepatitis B and chronic hepatitis C with HBV DNA level of 67.5 IU/mL and HCV RNA level of 3.33 x 106 IU/mL. She completed a 12 week course of sofosbuvir and velpatasvir for HCV and achieved sustained virologic remission, but subsequently developed reactivation of her HBV with HBV DNA peaking at 3.41 x 104 IU/mL twelve weeks post-treatment. She did not develop any signs of hepatitis and a decision was made to monitor her clinically.

Results

Two years later, she spontaneously went into remission with her HBV DNA levels being <10 IU/mL.

Conclusions

The significance of this case is to illustrate HBV reactivation following treatment of HCV with DAAs may not necessitate immediate treatment, especially if there are no signs of flare. There have been similar reported cases, but larger prospective studies are required to determine the appropriate clinical context where monitoring may be acceptable instead of immediate treatment.

Funding Agencies

None
A215 MDR3 DEFICIENCY MIMICKING WILSON DISEASE
Authors: Flanagan M , Little R , Siddiqui I , Jones N , Ng V
Published: March 2021

Background

The chronic phenotype of ALF includes a broad differential diagnosis. Class III multi-drug resistance P-glycoprotein 3 (MDR3) deficiency, also referred to as progressive familial intrahepatic cholestasis type 3, is an autosomal recessive genetic disorder. It is caused by a defect on the ABCB4 gene located on chromosome 7, which encodes MDR3. MDR3 is responsible for transporting phosphatidylcholine across the canalicular membrane, thereby allowing it to be incorporated into bile micelles. MDR3 deficiency results in increased levels of free bile acids and detergent bile. Progressive cholangiopathy ensues from this detergent bile and indirectly leads to cholestasis and liver failure in severe cases. Significantly increased urinary and hepatic copper (Cu), which are hallmarks of Wilson disease, have also been reported in patients with acute hepatitis and cholestasis including patients with MDR3 deficiency

Aims

We report a case of a girl who presented with a chronic phenotype of PALF, who had multiple features of Wilson disease and so was treated as such until genetic analysis confirmed MDR3 deficiency

Methods

Results

A 6 year old girl presented to the ED with a 1mth history of epistaxis and a 1wk history of abdominal pain and distension, facial edema, pallor and fever. Her family history was significant for parental consanguinity and maternal itch during pregnancy. On examination she had clubbing, scleral icterus and a distended abdomen with hepatosplenomegaly. Her bloodwork showed bicytopenia (HGB 53 & Plts 63) along with liver dysfunction (INR 2.9, albumin 25, conjugated bilirubin 9) and raised liver enzymes (transaminases & GGT >10xULN). Her total serum bile acids were raised at 134. An US showed hepatosplenomegaly with multiple hyperechoic nodules and perisplenic varices. She was extensively worked up for malignancy, autoimmune and metabolic disease. Serum ceruloplasmin was reduced, ophthalmology examination showed no KF rings and her 24hr urinary Cu was 10xULN. Liver Cu quantification was markedly raised at 40xULN. Liver biopsy showed cirrhosis with fibrosis related minimal non-specific portal and septal inflammation. Additionally, complete loss of canalicular staining on immunohistochemistry for MDR3 protein was noted, suggestive of MDR3 deficiency. Based on the Cu levels, a provisional diagnosis of Wilson disease was made and Cu chelation therapy was commenced pending genetic testing. A cholestatic gene panel subsequently showed homozygous pathogenic variant for the ABCB4 gene. Trientine was stopped and she was commenced on ursodeoxycholic acid. Though biochemically she remains largely unchanged, she is clinically stable whilst awaiting a liver transplant

Conclusions

This case highlights the diagnostic difficulties associated with Cu test result interpretation in patients with chronic cholestatic liver disease and urges a thorough consideration of alternative diagnoses of PALF

Funding Agencies

None
A216 CLINICAL MANIFESTATIONS OF LYSOSOMAL ACID LIPASE DEFICIENCY (LAL-D): THE INTERNATIONAL LAL-D REGISTRY
Authors: Francis M , Balwani M , Balistreri W , D’Antiga L , Fang S , Jones S , Ros E , Abel F , Wilson D
Published: March 2021

Background

Lysosomal acid lipase deficiency (LAL-D) is a rare, autosomal recessive disease caused by pathogenic variants in the LIPA gene. Lysosomal accumulation of cholesteryl esters and triglycerides leads to cirrhosis and dyslipidemia across a clinical spectrum, and affect both infants and children/adults.

Aims

An international registry (NCT01633489; Alexion Pharmaceuticals, Inc.; 2013–ongoing) was established to better understand the natural history of lysosomal acid lipase deficiency (LAL-D) and to evaluate long-term treatment outcomes.

Methods

Baseline findings for patients enrolled through July 1, 2019 are presented. Of 190 patients enrolled, 35 were excluded from this analysis (LIPA carrier, deceased at enrollment, unconfirmed LAL-D diagnosis); 155 patients with confirmed LAL-D diagnosis were included (12 infants, 143 children/adults). LAL enzyme activity analysis was performed for 145/154 patients (94%) and genetic testing for 128/154 patients (83%).

Results

Of 105 children/adults with reported LIPA mutations, 39 were homozygous and 34 were compound heterozygous for the common LIPA mutation E8SJM (c.894G>A); 6 infants with reported LIPA mutations were homozygotes and 2 were compound heterozygotes. Of the 155 patients, 62% were <18 years, 52% were male, and 85% were white. Median (range) age at clinical onset was 0.2 years (0.0–0.7) among infants and 6.0 years (0.0–41.3) among 133 children/adults with data; median (range) age at diagnosis was 0.2 years (−0.1 to 1.2) among infants and 10.8 years (0.2–53.6) among 135 children/adults with data. Manifestations that raised suspicion of LAL-D were reported in 149/155 patients. Infants (12 with data) presented predominantly with hepatomegaly (75%), splenomegaly (58%), nausea/vomiting (58%), and diarrhea (50%), and 50% had a known family history of LAL-D. Children/adults (n=143) presented predominantly with elevated alanine aminotransferase levels (67%), hepatomegaly (66%), and elevated aspartate aminotransferase levels (65%). Of 74 children/adults with baseline liver biopsy, 58% had microvesicular steatosis, 16% had micro- and macrovesicular steatosis, and 32% had lobular inflammation. Of the 155 patients, 6% had a medical history of cirrhosis. Analyses exploring the genotype-phenotype relationship will be presented.

Conclusions

Registry data of >150 LAL-D patients demonstrate early symptom onset, variable clinical manifestations, and a significant diagnostic delay in children/adults.

Funding Agencies

Alexion Pharmaceuticals, Inc.
A229 PROMOTION OF COLONIC ANASTOMOTIC HEALING WITH PERIOPERATIVE SUPPLEMENTATION WITH OLIGOSACCHARIDES
Authors: Hajjar R , Oliero M , Cuisiniere T , Fragoso G , Calve A , Djediai S , Annabi B , Richard C , Santos M M
Published: March 2021

Background

Colorectal resection is a standard procedure in the management of colorectal cancer (CRC) and inflammatory bowel disease. Anastomotic leak (AL) is a major complication in colorectal resections, and the gut microbiota may play a role in the healing and development of AL. Short-chain fatty acids (SCFAs), namely butyrate, have been involved in anastomotic healing when administered into the bowel via enema. Due to the mechanical stress associated with enemas after the confection of a fresh and fragile anastomosis, other butyrate-increasing strategies are required.

Aims

To promote anastomotic healing and prevent AL by using inulin and galacto-oligosaccharides (GOS) supplementation to modulate the microbiota toward a butyrate-producing profile.

Methods

Mice were fed diets supplemented with inulin, GOS or cellulose, as a non-fermentable control, for two weeks and underwent a proximal colonic anastomosis under general anesthesia. Healing of the anastomosis, both macroscopically and microscopically, was assessed six days after surgery. Epithelial proliferation, mucus production and integrity of the gut barrier were assessed.

Results

Inulin and GOS supplementation increased SCFAs in the colon and were associated with better postoperative weight recovery and macroscopic anastomotic healing. Microscopically, mucosal continuity was promoted by inulin and GOS. Mucus production was found to be similar in all groups. The gut barrier was found to be improved with inulin and GOS as shown by less bacterial translocation.

Conclusions

Inulin and GOS may prevent AL and promote anastomotic healing. This effect appears to be mediated by improved mucosal proliferation.

Funding Agencies

CIHRNatural Sciences and Engineering Research Council of Canada; Institut du cancer de Montréal; Fonds de recherche du Québec en santé
A230 ISOMALTODEXTRIN DOSE-DEPENDENTLY REDUCES COLITIS DEVELOPMENT IN HLA-B27 RAT COLITIS MODEL WITH ASSOCIATED CHANGES TO GUT MICROBIOME COMPOSITION AND SHORT CHAIN FATTY ACID PRODUCTION
Authors: Premraj N , Valcheva R , Dieleman L A
Published: March 2021

Background

Inflammatory bowel disease (IBD) is characterized by altered intestinal microbiome (i.e. dysbiosis), described by reduced strict butyrate-producing anaerobes versus increased facultative anaerobes. Data from preclinical studies and clinical trials show prebiotic inulin-type fibers can prevent and reduce colitis. However, other dietary fibers (e.g. resistant starches, RS) are understudied and it is unknown if RS-induced microbial shifts are protective in experimental colitis.

Aims

Assess efficacy of isomaltodextrin (IMD), a novel RS, to reduce intestinal inflammation in HLA-B27 transgenic (TG) rat colitis model and identify protective mechanisms associated with gut microbial composition and function.

Methods

4 week old HLA-B27 TG rats were fed standard chow supplemented with: 7.5% IMD (low dose, LD), 15% IMD (high dose, HD), negative control (15% cellulose, NC), or positive control (15% fructooligosaccharides, PC) for 12 weeks. Body weight and food intake were measured. Cecal and colonic inflammation assessed by weight/length ratio, macroscopic scoring and mucosal IL-1β secretion. Changes in microbial energy metabolism evaluated by measuring short chain fatty acid (SCFA) production in stool and cecal contents. Endpoint fecal and cecal microbiota composition differences assessed by 16S rRNA gene sequencing (Illumina MiSeq platform).

Results

IMD showed dose-dependent effect on cecal inflammation, measured by macroscopic tissue scoring, weight/length ratio and IL-1β secretion. HD rats had significantly lower cecum IL-1β concentration compared to NC (q=0.01), while LD showed only a trend (q=0.09). HD had significantly higher cecal amounts of Bacteroidaceae and Allobaculum spp. and lower amounts of Peptostreptococcaceae, Eubacterium and Barnesiella spp. versus the LD and NC. HD was associated with significantly higher total SCFA compared to NC (q<0.01) and showed a trend of higher total SCFA than LD (q=0.06). Analysis of SCFAs revealed propionate, isobutyrate and valerate ratios were significantly lower in HD than LD and NC. HD showed a trend of higher ratio of butyrate + acetate compared to NC. This suggests increased carbohydrate fermentation by acetate-producing and -converting microbial groups. Correlation analysis confirmed IL-1β concentrations were positively associated with isobutyrate (r=0.52, q<0.01), valerate (r=0.54, q<0.01), and propionate (r=0.48, q<0.01), suggesting their use as chronic inflammation markers in HLA-B27 models.

Conclusions

IMD was dose-dependently effective in reducing chronic cecal inflammation in experimental colitis. Benefits were associated with specific shifts in gut microbiome composition and SCFA production. Results from this preclinical study warrant future microbiota-altering intervention trials using IMD in clinical IBD.

Funding Agencies

Hayashibara Co., Ltd.
A234 EVALUATING THE EFFECT OF STOOL SUPERNATANTS FROM IBS PATIENTS AND HEALTHY CONTROLS ON THE EXCITABILITY OF DRG NEURONS
Authors: Neary E , Jiménez-Vargas N N , Osman S , Reed D E , Vanner S , Lomax A E
Published: March 2021

Background

Abdominal pain is commonly described in chronic disorders such as irritable bowel syndrome (IBS), but the underlying mechanisms are currently unclear. The stool metabolomic and microbiota profiles of IBS and healthy patients have shown distinct differences. Additionally, IBS stool supernatants have previously been demonstrated to induce hypersensitivity of nociceptive nerves in the ex vivo mouse colon, suggesting that mediators in the stool can sensitize nociceptors. However, the effects of healthy control (HC) or IBS patient stool supernatants on the excitability of DRG neurons have not been clarified.

Aims

To evaluate the effect of HC and IBS supernatant on DRG neurons.

Methods

HC (n=8 patients) or IBS (n=10 patients) stool was collected, dissolved and homogenized with bicarbonate-buffered Krebs solution at 37°C in a 1/10 dilution. DRG neurons from C57BL/6 mice were dissociated and incubated overnight with HC or IBS supernatant in a Krebs dissolution. Changes in DRG neuronal excitability were recorded using perforated patch-clamp techniques to measure the rheobase (amount of current needed to elicit an action potential). The effect of the IBS and HC stool supernatants on the resting membrane potential (RMP) was also recorded.

Results

Overnight incubations with supernatant of HC stool diluted in Krebs solution (n=28 neurons) did not significantly decrease the rheobase compared to control neurons (n=22) (62.7 ± 3.9 pA vs 64.2 ± 2.7 pA). In a parallel experiment, we evaluated the effect of IBS stool supernatants diluted in Krebs (n=52 neurons) and found that they significantly decreased the rheobase compared to the supernatant of HC diluted in Krebs and control neurons (52.3 ± 2.3; p<0.05). The data were analyzed with a one-way ANOVA and Tukey’s test. Incubations with IBS supernatant decreased the RMP compared to HC supernatant (-42.6 ± 0.6 mV vs. -46.0 ± 0.9 mV; p<0.01), which was calculated with an unpaired t-test.

Conclusions

These findings suggest that mediators in IBS stool increase the excitability of DRG neurons compared to HC stool supernatant, and thus may contribute to pain signaling in IBS patients.

Funding Agencies

CIHR
A242 THE AIR BETWEEN US: A CASE OF PSEUDOCYST PERFORATION POST-ENDOSCOPIC CLIPPING OF A BLEEDING PANCREATIC-COLONIC FISTULA
Authors: Sedarous M , Balubaid I , Basden A , Rahman A
Published: March 2021

Background

Pancreatic fistula is an uncommon complication of pancreatitis and is associated with increased morbidity. We discuss a case of pancreatic-colonic fistulization followed by the first reported case of pseudocyst perforation post-colonoscopy.

Aims

Case

Methods

A 51 year-old female with decompensated alcoholic cirrhosis admitted with hepatic encephalopathy developed large volume hematochezia during admission. Past medical history includes pancreatic pseudocyst, GERD and remote hernia repairs. For the hematochezia, she was investigated with an EGD and colonoscopy. In the distal descending colon, a bleeding lesion was identified and treated with clips and epinephrine injection (Figures 1 and 2). Five hours post-procedure, she developed abdominal distention. CT abdomen pelvis revealed large volume of free air and simple fluid within the abdominal cavity likely secondary to rupture pseudocyst rupture. The previously visualized pseudocyst was filled with gas plastered against the descending colon. She remained medically stable with conservative management.

Results

Discussion

Conclusions

Pancreatic-colonic fistula is an uncommon but potentially life-threatening complication of acute pancreatitis associated with high risk of complications. They are found in 4% of admitted inpatients with acute pancreatitis. There are three proposed mechanisms for their development: firstly, inflammation and activated pancreatic lytic enzymes; secondly, pressure necrosis from a contiguous mass; thirdly, localized portal hypertension. Classically, pancreatic-colonic fistulas present with diarrhea, fever and hematochezia. Gastrointestinal bleeding occurs in 60% of cases. The source of bleed has been described to be originating most commonly from the splenic artery and to a lesser extent, the margin of the fistula or, rarely, erosion of splenic parenchyma. Reported therapeutic management strategies include: hemoclippings and Greenplast sprayings, endoscopic pancreatic stent, transgastric nasocystic drainage catheter placements, injection of N-butyl-2-cyanocrylate and transpapillary nasopancreatic drainage.

Pseudocysts arise in 25% of patients with chronic pancreatitis. Pseudocysts may regress through a variety of mechanisms: spontaneously after inflammation from pancreatitis resolves, natural drainage through the pancreatic duct into the duodenum, or through a complicating fistulous tract connecting to the gastrointestinal tract. Rarely, the pseudocyst can resolve as it leaks or perforates into the abdominal cavity. Pancreatic pseudocysts may perforate spontaneously into the free peritoneal cavity, stomach, duodenum, colon, portal vein, pleural cavity, or through the abdominal wall. We report the first case, to our knowledge, of pancreatic pseudocyst perforation post-clipping of bleeding pancreatic-colonic fistula.

Funding Agencies

None
A243 A RETROSPECTIVE REVIEW OF THE RADIOGRAPHIC DIAGNOSIS AND SURGICAL RESECTION RATES OF PANCREATIC SEROUS CYSTS
Authors: Monachese M , Li S , Salim M , Guimaraes L , James P D
Published: March 2021

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
Subterranean Termite (Coptotermes gestroi(Blattodea: Rhinotermitidae)) Colony Elimination Through Exposure to a Novaluron CSI Bait Formulation in Laboratory
Authors: Chouvenc Thomas
Published: March 2021

The development of baits for subterranean termite control over the past 25 yr has provided cost-effective alternatives to liquid termiticide treatments. Current bait products use one of the few available benzoylurea chitin synthesis inhibitors (CSIs) labeled for subterranean termites. These insecticides are used because of their nonrepellency, their slow-acting mode of action, and their dose-independent lethal time. Although many studies have provided ample evidence of the efficacy of CSI baits for subterranean termite colony elimination, most have focused on hexaflumuron and noviflumuron. However, bait products using alternative CSIs have not received the same level of scrutiny, limiting the amount of evidence proving their efficacy. One such compound is novaluron, the active ingredient currently used in the Trelona ATBS—Advance Termite Baiting System bait product. The current study independently tested the efficacy of this commercially available bait formulation against whole colonies of Coptotermes gestroi (Wamann) (~63,910 workers) in the laboratory, using an extended experimental setup to simulate a 15-m foraging distance from the central part of the nest to the bait, while having access to alternative food sources. Treated colonies progressively ceased to feed on wood items within 45 d after being provided access to the novaluron bait formulation, with a subsequent progressive collapse of the population, leading to colony elimination by 91 d. This study therefore confirms the efficacy of novaluron baits against subterranean termites, and currently remains one of the few CSIs that can be applied for the successful control of Coptotermes infestations.