Evidence Of Colitis Research Articles

Modelling a Western Lifestyle in Mice: A Novel Approach to Eradicating Aerobic Spore-Forming Bacteria from the Colonic Microbiome and Assessing Long-Term Clinical Outcomes.

The environmentally acquired aerobic spore-forming (EAS-Fs) bacteria that are ubiquitous in nature (e.g., soil) are transient colonisers of the mammalian gastro-intestinal tract. Without regular exposure, their numbers quickly diminish. These species of bacteria have been suggested to be essential to the normal functioning of metabolic and immunogenic health. The modern Western lifestyle restricts exposure to these EAS-Fs, possibly explaining part of the pathogenesis of many Western diseases. To date, the only animal studies that address specific microbiome modelling are based around germ-free animals. We have designed a new animal model that specifically restricts exposure to environmental sources of bacteria. A new protocol, termed Super Clean, which involves housing mice in autoclaved individually ventilated cages (IVCs), with autoclaved food/water and strict ascetic handling practice was first experimentally validated. The quantification of EAS-Fs was assessed by heat-treating faecal samples and measuring colony-forming units (CFUs). This was then compared to mice in standard conditions. Mice were housed in their respective groups from birth until 18 months. Stool samples were taken throughout the experiment to assess for abundance in transiently acquired environmental bacteria. Clinical, biochemical, histological, and gene expression markers were analysed for diabetes, hypercholesterolaemia, obesity, inflammatory bowel disease, and non-alcoholic fatty liver disease (the "diseases of the West"). Our results show that stringent adherence to the Super Clean protocol produces a significantly decreased abundance of aerobic spore-forming Bacillota after 21 days. This microbiomic shift was correlated with significantly increased levels of obesity and impaired glucose metabolism. There was no evidence of colitis, liver disease or hypercholesterolaemia. This new murine model successfully isolates EAS-Fs and has potential utility for future research, allowing for an investigation into the clinical impact of living in relative hygienic conditions.

Immune checkpoint inhibitor-induced gastrointestinal injury: prevalence of cytomegalovirus, adenovirus and Epstein-Barr virus

AimsWidespread use of immune checkpoint inhibitors (ICIs) for treatment of advanced malignancies led to an increase in number of immune-related adverse events such as ICI gastrointestinal (GI) injury (ICIGI). The...

Gut Immunomodulation with Vedolizumab prior to Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients with Inflammatory Bowel Disease

Inborn errors of immunity (IEI) are often associated with inflammatory bowel disease (IBD). IEI can be corrected by allogeneic hematopoietic stem cell transplantation (HSCT); however, peritransplantation intestinal inflammation may increase the risk of gut graft-versus-host disease (GVHD). Vedolizumab inhibits the homing of lymphocytes to the intestine and may attenuate gut GVHD, yet its role in preventing GVHD in pediatric patients with IEI-associated IBD has not been studied. Here we describe a cohort of pediatric patients with IEI-associated IBD treated with vedolizumab before and during allogeneic HSCT. The study involved a retrospective chart review of pediatric patients with IEI-associated IBD treated with vedolizumab at 6 weeks, 4 weeks, and 1 week before undergoing HSCT. The conditioning regimen consisted of treosulfan, fludarabine, and cyclophosphamide with rabbit antithymocyte globulin, and GVHD prophylaxis included tacrolimus and steroids. Eleven patients (6 females) with a median age of 5 years (range, .4 to 14 years) with diverse IEI were included. IBD symptoms were characterized by abdominal pain, loose stools, and blood in stools. Four patients had developed a perianal fistula, and 1 patient had a rectal prolapse. One patient had both a gastrostomy tube and a jejunal tube in situ. Treatment of IBD before HSCT included steroids in 11 patients, anakinra in 2, infliximab in 4, sulfasalazine in 2, mesalazine in 2, and vedolizumab. IBD symptoms were considered controlled in the absence of abdominal pain, loose stools, or blood in stools. Graft sources for HSCT were unrelated donor cord in 5 patients (2 with a 5/8 HLA match, 2 with a 7/8 match, and 1 with a 6/8 match), peripheral blood stem cells in 5 patients (2 haploidentical, 1 with a 9/10 HLA match, and 2 with a 10/10 match), and bone marrow in 1 patient (10/10 matched sibling donor). The median number of vedolizumab infusions was 4 (range, 3 to 12) before HSCT and 1 (range, 1 to 3) after HSCT, and all were reported to be uneventful. All patients had engrafted. Acute GVHD occurred in 4 patients and was limited to grade I skin GVHD only. Chronic GVHD occurred in 1 patient and again was limited to the skin. There was no gut GVHD. Three patients experienced cytomegalovirus viremia, and 2 patients had Epstein-Barr virus viremia. At the time of this report, all patients were alive with no evidence of IBD at a median follow-up of 15 months (range, 3 to 39 months). Administration of vedolizumab pre- and post-HSCT in pediatric patients with IEI-associated IBD is well tolerated and associated with a low rate of gut GVHD. These findings provide a platform for the prospective study and use of vedolizumab for GVHD prophylaxis in pediatric patients with known intestinal inflammation as a pre-HSCT comorbidity.

A166 STEROID-REFRACTORY ILEITIS FOLLOWING RITUXIMAB THERAPY: A CASE REPORT AND LITERATURE REVIEW

Abstract Background Rituximab, an anti-CD20 monoclonal antibody commonly used in treatment of hematologic and rheumatologic disease is generally well-tolerated from a gastrointestinal perspective however rare reported side effects include diarrhea and enterocolitis. Aims We describe a case of steroid-refractory ileitis presenting in a woman with follicular lymphoma post Rituximab therapy. Methods A case report and literature review were performed. Results A 73-year-old woman presented with a 4-week history of fevers, bloody diarrhea and abdominal pain. She had a known history of stage IV follicular lymphoma treated with six cycles of Bendamustine and Rituximab followed by four doses of maintenance Rituximab, with the last dose ending 4 weeks prior to her presentation. On examination, she had multiple peri-anal round ulcers. An abdominal CT revealed circumferential mural thickening involving the distal terminal ileum. On colonoscopy, there were multiple discrete ulcers and nodularity in the terminal ileum. Pathology showed evidence of chronic active ileitis with no signs of malignancy, lymphoproliferative disorders, or granulomas. AFB smear and cultures were negative. She was given IV steroids for 1 week and then placed on a Prednisone taper scheduled to finish in 9 weeks. 4 weeks later she presented again with fevers and abdominal pain. Inflammatory markers were elevated, and a repeat CT abdomen showed ongoing multifocal ileitis. She was put back on IV steroids and monitored. She continued to have persistent abdominal pain and fevers, and then underwent a repeat colonoscopy after 9 days of IV steroids which showed an interval increase in the size of her ileal ulcers. Pathology showed granulation tissue and reactive changes with no evidence of malignancy, lymphoma, granulomas, inclusion bodies or other viral cytopathic effects. Repeat AFB smear was negative. CMV PCR in blood was negative. She was assessed for Behcet’s disease (BD) given her peri-anal ulcers however she lacked other findings needed to fulfill the diagnostic criteria for BD. Steroids were continued with plans to initiate biological therapy. A review of literature revealed rare reports of rituximab-associated ileocolitis and development of de novo inflammatory bowel disease post rituximab therapy. Among patients who received Rituximab and underwent Colonoscopy, 4% had evidence of colitis. Rituximab-associated colitis appears to be usually mild presenting with diarrhea and requiring supportive care only, but in rare cases can lead to fulminant colitis and bowel perforation. Conclusions Rituximab-associated enterocolitis remains an under-reported entity and can lead to significant morbidity and treatment-associated challenges requiring prolonged courses of steroids and considerations for biological therapies. Important differentials to consider include malignancy, lymphoma, Tuberculosis, Bechet’s disease, and CMV enterocolitis. Ulcer in terminal ileum and ileocecal valve - Pre steroids (Left), Post steroids (Right) Funding Agencies None

P1139 Lymphocytic Colitis: A large case series in the United Kingdom

Abstract Background Lymphocytic colitis, a type of microscopic colitis, was previously thought to be a rare condition. It is a histological diagnosis characterised by chronic loose stools and normal findings on endoscopy. It is now thought that it could be implicated in up to 10% of people with chronic diarrhoea, and has traditionally been associated with certain medications. We conducted a retrospective case analysis of patients diagnosed with the condition on histology between January 2018 till December 2022. Methods A list of patients who had undergone colonoscopy and biopsy for chronic diarrhoea, with no evidence of inflammatory bowel Disease (IBD), was generated. The patient’s electronic health records were then manually analysed, and data was collected using certain parameters including presence of autoimmune disease, faecal calprotectin levels/QFIT, smoking status, medication use (NSAIDS, PPI, Statins or SSRIs), colonoscopy findings, treatment choice and treatment outcomes. 121 patients were eligible based on histopathology consistent with a diagnosis of lymphocytic colitis. Results The median age was 63, with a 3:2 split of female to male patients. 63% reported painless, chronic diarrhoea lasting more than 6 weeks. 10.7% had painless and bloody diarrhoea, 23% had diarrhoea with abdominal pain. 25.4% had evidence of autoimmune disease. 43% were taking a PPI, 6.6% and NSAID, 41% a statin and 25.6% an SSRI. 27% were active smokers at the time of presentation. 62.8% of patients had a normal colonoscopy report, with the rest having ‘’abnormal reports” due to polyps. Faecal calprotectin levels ranged from 20-954. QFIT was positive in 35% of patients. 34% of patients were treated under a gastroenterologist. Of those who received budesonide only: 46% recovered with no relapse, 20% had relapsed in under 6 months, 16% relapsed after 6 months, 16% did not present again. Of the patients who received loperamide only, 66% reported resolution of symptoms. All histology demonstrated lymphocytosis in the lamina propria, 16% had expansion of the subepithelial collagen band, often termed ‘incomplete Microscopic colitis’. Conclusion Use of PPIs, statins and SSRIs are highly represented in the data, compared with general population usage. Treatment with either budesonide or loperamide generally lead to better symptom control, indicating patients should be referred to gastroenterology upon diagnosis. Clinicians should judiciously prescribe the above medications with clear indication and avoid prescribing indefinitely.

S2711 Biologic Therapies for Isolated Recurrent, Persistent Complex Perianal Fistulas Without Luminal Crohn's Disease

Introduction: Isolated complex perianal fistulas are abnormal connections between the epithelial surfaces of the anal canal and the perianal skin, meeting criteria for complex perianal fistula but without evidence of inflammatory bowel disease (IBD). While over half of patients with Crohn’s disease (CD) have perianal fistulas, isolated perianal CD is rare. Here we discuss five cases of patients presenting with isolated recurrent complex perianal fistula, and we describe their diagnostic evaluation, attempted therapies, and outcomes. Case Description/Methods: Five adults (3 women, 2 men; mean age 38 years old) with no prior GI symptoms/diseases initially presented with perianal pain (3/5), perirectal mass (2/5), diarrhea (1/5), and abdominal pain (1/5) (Table). All patents underwent exam under anesthesia (EUA) with incision and drainage (I&D) of perirectal abscesses, and setons were placed in perianal/rectal fistulas in 4/5 cases. Each patient had colonoscopy without evidence of inflammation on endoscopy or histology. Radiographic imaging (MRIs, MREs, and CT) revealed fistulas and abscesses but no evidence of luminal inflammation. All patients were treated with antibiotics and 4/5 received biologic therapy (Adalimumab, Infliximab, or Ustekinumab). Despite surgical and medical management, complex perianal fistulas were persistent in all patients at follow-up after an average of 45 months. Discussion: For patients who develop recurrent complex fistulas, a presumptive diagnosis of CD is often made. However, patients who present with complex perianal fistulas in the absence of the luminal inflammation characteristically found in CD are said to have isolated perianal disease (IPD). It is unclear whether IPD represents truly isolated severe cryptoglandular fistulas or early presentation of undiagnosed CD, which renders the best treatment approach a clinical dilemma. IPD is classically treated with antibiotics and local surgical intervention, whereas perianal CD treatment is more complex, incorporating the use of immunosuppressive therapy. The cases described in our cohort reveal the importance of a multimodal approach when treating IPD in the absence of luminal findings of CD. While classic medications for CD are unlikely to succeed when used alone for IPD, their incorporation into the treatment regimen may be critical in achieving eventual resolution of perianal disease. Given the similarity in management, it is important to consider CD in the differential for IPD patients even in the absence of luminal findings. Table 1. - Patient Summary PT # Initial Presentation Diagnostic Evaluations Subsequent Diagnosis Medical Therapies Attempted Surgical Procedures Ultimate Diagnosis and Plan (1) 39F Painful perianal mass, presumed to be an abscess or hemorrhoids Flexible sigmoidoscopyColonoscopy with bxMRIEUA Refractory perirectal and rectovaginal fistula with abscess IBD medications: AdalimumabMethotrexate Non-IBD medical therapies: CiprofloxacinMetronidazoleAmoxicillin-Clavulanic acidPrednisone I&DSeton placementFistulectomy with sphincterotomyDiverting sigmoid colostomyFistulotomy Non-healing cryptoglandular anal fistula complicated by surgery Discontinue IBD therapySurgical f/u with consideration for clinical trial of stem cell injection or transperitoneal repair (2) 34M Abdominal pain, diagnosed with sigmoid diverticulitis Colonoscopy with bxMRIMRECT scanEUA Refractory perianal fistula with abscess IBD medications: InfliximabUstekinumabTacrolimusAzathioprine Non-IBD medical therapies: MetronidazoleCiprofloxacin I&DSeton placement Isolated perianal disease in the setting of presumed CD Chronic treatment with chronic, cyclical abx (Ciprofloxacin or Amoxicillin-Clavulanic acidIBD-directed therapy (Azathioprine + Infliximab; will consider Upadacitinib once approved by the FDA)Planning for surgical f/u (3) 43M Painful perianal mass, presumed to be a rectal abscess Colonoscopy with bxMRIEUA Refractory perianal abscess Non-IBD medical therapies: Amoxicillin-Clavulanic acid I&D Isolated cryptoglandular abscess with potential hemorrhoids No need for chronic antibioticsSitz baths and PrepH as neededIf symptoms worsen will plan for EUA and surgical f/u (4) 24F Perianal pain, diagnosed as perianal abscess with fistula Colonoscopy with bxMRIEUA Refractory perianal abscess, inflammatory arthropathy IBD medications: AdalimumabInfliximabAzathioprine Non-IBD medical therapies: CiprofloxacinMetronidazole I&DSeton placement Presumed CD with perianal disease and inflammatory arthropathy IBD-directed therapy (Azathioprine + Infliximab)Planning for surgical f/u (5) 50F Diarrhea and rectal ulcers, presumed to have CD Colonoscopy with bxMRICTEUA Refractory perianal fistula with abscess IBD medications: Infliximab Non-IBD medical therapies: ColchicinePrednisone I&DSeton placementPerineal debridementLay open fistulotomy Presumed CD with perianal disease IBD-directed therapy (Infliximab) Abbreviations: Bx = biopsies. CD = Crohn’s disease. EUA = exam under anesthesia. F = female. F/U = follow up. I&D = incision and drainage. IBD = inflammatory bowel disease. M = male. MRE = magnetic resonance elastography. MRI = magnetic resonance imaging

Pyoderma Gangrenosum in Systemic Lupus Erythematosus: An Uncommon Association

Pyoderma gangrenosum (PG) is a type of neutrophilic diseases and is an uncommon, idiopathic, ulcerative dermatosis. On the contrary, systemic lupus erythematosus (SLE) is a chronic, autoimmune, multisystem, progressive disease that causes widespread inflammation in joints, skin, blood vessels, and several other organs. The rash of SLE is usually on photo-distributed areas, especially the face. PG-like ulceration was previously reported with antiphospholipid antibody syndrome; however, the association of PG and SLE is rarely observed. We report a rare manifestation of SLE presenting as ulcerative PG in a 46-year-old female who was diagnosed with SLE with no evidence of inflammatory bowel disease, rheumatoid arthritis, chronic active hepatitis, monoclonal gammopathies, and hematological malignancies. She developed a skin lesion on her right breast region which was later diagnosed to be PG following biopsy and was managed with corticosteroids and appropriate wound management.

Inflammatory bowel disease manifestations in spondyloarthritis: considerations for the clinician

ABSTRACT Introduction Spondyloarthropathies (SpA) are a group of inflammatory arthritis that can involve the spine and/or peripheral joints. Extra-articular manifestations, such as inflammatory bowel disease (IBD), are frequently observed within the clinical manifestations of SpA and are part of the SpA classification criteria. Evidence of IBD is observed in about 6–7% of SpA patients, and a silent, microscopic gut inflammation, could be present in up to 50% of patients. From a pathogenetic point of view, dysregulated microbiome and migration of T lymphocytes and other cells from gut to the joint (‘gut-joint’ axis) has been recognized, in the context of a common genetic background. Areas covered The aim of this paper is to narratively review the recent evidences on the epidemiology, classification, clinical findings, pathogenesis, diagnosis, and treatment of IBD in patients with SpA and to provide advices for both rheumatologist and gastroenterologist in the management of IBD in SpA. Expert opinion IBD manifestations in SpA frequently increase the burden of the disease and represent a clinical challenge, especially for the diagnosis, assessment, and treatment of patients affected by those conditions. New treatment strategies targeting both articular and intestinal manifestations are now available and may lead to a better outcome.

AKAP12/Gravin is over-expressed in patients with ulcerative colitis

The gene of A-kinase anchor protein 12 (AKAP12) regulates cell cycle progression, cell motility, and morphology through its multiple scaffolding domains. However, the role of AKAP12 expression in ulcerative colitis (UC) patients has not been yet described. The aim of the study was to describe the gene and protein of AKAP12 expression in patients with UC and its association regarding the disease severity. We included a total of 40 patients with confirmed diagnosis of UC and 25 controls without endoscopic evidence of colitis or neoplasia. The relative quantification of the gene expression was performed by real-time PCR for AKAP12. Kruskal-Wallis was used to test differences among groups, and Spearman correlation to assess the relationship between AKAP12 gene and clinical outcomes. The extent of disease was evaluated using total colonoscopy, and biopsies were taken from rectum segments. The AKAP12 gene expression was increased in colonic mucosa from patients with active UC when compared with UC remission and control group. The overexpression of AKAP12 in patients with UC was associated with the presence of extensive colitis (p = 0.04, RM = 12, IC = 1.29-186.37). AKAP12/CD16 double positive cells were higher in submucosa (p = 0.04), muscular (p < 0.001), and cells from serosa (p < 0.001) in patients affected by UC in comparison to controls. The overexpression of AKAP12 was associated with the extent of disease. This is the first report about the role of AKAP12 in patients with UC suggesting that this gene and its protein could be involved in the modulation of the disease.

A19 HEALTH CARE UTILIZATION DIFFERENCES BETWEEN FIRST NATIONS AND THE GENERAL POPULATION WITH INFLAMMATORY BOWEL DISEASE IN SASKATCHEWAN

Abstract Background Indigenous patients with inflammatory bowel disease (IBD) have expressed concerns about barriers to access IBD care. The limited evidence of IBD among Indigenous people highlights the need for studies evaluating access to IBD care in this population. Aims We aimed to compare health care utilization between First Nations (FNs) and individuals from the general population (GP) diagnosed with IBD in Saskatchewan (SK). Methods A population-based retrospective cohort study was conducted using administrative health databases of SK from 1998 to 2017 fiscal years. As a patient-oriented research initiative, outcomes of interest were chosen in collaboration with Indigenous patients and family advocates. A validated algorithm requiring multiple health care contacts was applied to identify incident IBD cases. The self-declared FN status variable was used to divide IBD cases between FNs and the general population (GP). To balance the groups, 1:5 age and sex matching was applied. Cox-proportional models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CI). Stratified analysis was completed for those diagnosed before and after 2008 (pre- and post-biologic eras). Results A matched cohort with 696 IBD incident cases was created (FN=116, GP=580). Comparing health care utilization of FNs and individuals from the GP with IBD, there were no statistically significant differences in outpatient gastroenterology visits (FNs=81.0%, GP=83.6%), colonoscopies (FNs=91.4%, GP=86.9%), and surgeries for IBD (FNs=31.0%, GP=33.5%). We observed differences in prescription claims for any medication for IBD (FNs=79.3%, GP=89.3%) and 5-aminosalicylic acid (5-ASA) claims (FNs=75.9%, GP=81.4%). The HRs adjusted by rural/urban residence and diagnostic type showed differences in prescription claims for any IBD medication (HR=0.52, 95%CI 0.41–0.65) and 5-ASA (HR=0.57, 95%CI 0.45–0.72). In the pre-biologic era, FNs had a lower risk of having a prescription claim for any IBD medication (HR=0.32, 95%CI 0.23–0.45) and 5-ASA (HR=0.33, 95%CI 0.24–0.47), respectively. These differences were not significant in the post-biologic era. Conclusions Our study identified an inverse association between FN status and having prescription medication claims for IBD in SK. We considered multiple confounding variables when evaluating this association but could not control by disease severity. Thus, this association might reflect a barrier to access IBD medications or that FNs with IBD might present a milder disease. Further studies should continue evaluating access to IBD care, medication use, and disease severity among FNs living with IBD. Funding Agencies Saskatchewan Centre for Patient-Oriented Research (SCPOR), Saskatchewan Health Research Foundation (SHRF), and College of Medicine, University of Saskatchewan.

URINARY BLADDER NECROSIS - AN EXTRAINTESTINAL MANIFESTATION OF INFLAMMATORY BOWEL DISEASE IN A PEDIATRIC PATIENT

Abstract Extraintestinal manifestations are common in inflammatory bowel disease (IBD), and genitourinary complications are known, including nephrolithiasis, fistulas, and ureteral obstruction. Bladder involvement is less common, and limited to cystitis including xanthogranulomatous cystitis. Bladder necrosis has not been previously described in association with IBD. Here, we describe an unusual case of IBD associated with total bladder necrosis at the time of initial diagnosis. An 8-year-old female with a history of chronic microcytic anemia presented with 1 week of hematochezia, hematuria, and fever with associated abdominal pain. Her exam was significant for mild lower quadrant abdominal tenderness including the suprapubic area, but was otherwise unremarkable. Blood work showed microcytic anemia and mild thrombocytopenia, elevated inflammatory markers, and hypoalbuminemia. Infectious workup was unremarkable. Upon admission, she developed oliguria and hypertension and rapidly progressed to renal failure requiring dialysis catheter placement and renal replacement therapy. A kidney biopsy revealed acute tubular injury but showed no glomerular involvement and had no evidence of hemolytic uremic syndrome or vasculitis. Imaging obtained including CT of her abdomen showed a thickened transverse colon and a thickened bladder wall with dilation of the renal collecting system, worse on the left. Bladder biopsy showed full-thickness necrosis of unclear etiology and had negative staining for microorganisms. She had bilateral nephrostomy tubes placed for drainage of her kidneys and her renal function subsequently returned to normal. MR imaging also revealed necrosis and confirmed complete bladder involvement. Her renal failure was presumed to be a secondary to ureterovesical junction obstruction from the bladder necrosis. She underwent esophagogastroduodenoscopy (EGD) and colonoscopy due to persistent hematochezia. The EGD was unremarkable. Her colonoscopy was grossly abnormal with evidence of colitis from the cecum to the rectum. Biopsies revealed both active and chronic inflammation with sparing of the terminal ileum, and immunohistochemical staining for infection was negative. Capsule endoscopy was largely unremarkable. She was diagnosed with ulcerative colitis and started on steroids and sulfasalazine. Her abdominal pain and stool consistency improved and her bloody stools resolved. Steroids were tapered and she continued sulfasalazine as maintenance therapy. This case presents a novel association of IBD and bladder necrosis. Vascular obstruction secondary to a hypercoagulable state might explain such an event, but this seems less likely given the diffuse nature of bladder involvement. A clinical index of suspicion for bladder involvement and/or necrosis is warranted in patients with IBD who present with obstructive urinary symptoms or hematuria.

729. Real World Efficacy of Bezlotoxumab for Prevention of Clostridioides Difficile Recurrence in Immunosuppressed Patients

BackgroundBezlotoxumab has been shown to prevent recurrent episodes of C. difficile infection (CDI) in high risk patients. Current studies define therapeutic efficacy within the first 12 weeks when the risk of recurrence is greatest. However, the risk of recurrent CDI can occur beyond the 12-week window in the immunosuppressed population. Given that bezlotoxumab has detectable serum levels for up to 24 weeks after infusion, the primary endpoint is to determine overall efficacy in immunosuppressed patients with recurrent CDI at 4 weeks, 12 weeks, and 24 weeks after initial infusion. Secondary endpoints consist of risk factors for recurrent CDI, treatment of CDI, and antibiotics usage before and after bezlotoxumab.MethodsThis analysis included immunosuppressed patients at high risk for CDI recurrence who received bezlotoxumab from February 2017 to December 2019. Patients were excluded if they were not immunosuppressed, had no follow-up appointments, and/or without a C. difficile positive test. High risk antibiotics included fluoroquinolones, beta lactamase inhibitors, third generation cephalosporins, or carbapenems.ResultsTwenty-seven bezlotoxumab doses were given to 26 patients. Baseline characteristics for CDIs prior to bezlotoxumab is reported in Table 1. The overall CDI recurrence rate at all intervals after bezolotoxumab was 4 (15%), one recurrent CDIs occurred at < 4 weeks, two recurrent CDIs occurred at 5-12 weeks, and one recurrent CDI at 13-24 weeks. High risk antibiotics were given in 2/4 (50%) of CDIs recurrences and 22/75 (29%) in the non-recurrence group. Of the four CDI recurrences, all were mild to moderate in disease severity given no evidence of colitis was seen on CT scan and a median Zar score of 1 (range 0-1) due to age > 60 years.Table 1: Baseline Characteristics ConclusionIn immunosuppressed patients with CDI, bezlotoxumab is effective at reducing CDI episodes up to 24 weeks. Additionally, this highly antibiotic exposed population continued to receive benefit up to 24 weeks after bezlotoxumab.Disclosures All Authors: No reported disclosures

Segmental Diffuse Inflammatory Pseudopolyps Associated With Diverticulitis

Abstract Introduction/Objective Inflammatory pseudopolyps (IPs) often develop in response to chronic active inflammation in patients with inflammatory bowel disease (IBD). IPs can be diffuse and numerous in severe IBD. IPs can also occur from other chronic active injuries, such as ulcers, persistent infection, ischemic colitis, anastomotic site and diverticulitis. IPs arising from diverticulitis is uncommon and generally few in numbers. We report a rare case of a patient with segmental diffuse IPs associated with diverticulitis in the absence of IBD. Methods A 59-year-old male patient with a history of sigmoid diverticulitis presented with abdominal pain and was treated with antibiotics. Three months later he had severe recurrent diverticulitis. CT scan showed wall thickening of the sigmoid colon and multiple sigmoid diverticula. Colonoscopy showed extremely severe inflammatory colitis in the area of diverticulitis between 25.0 and 35.0 cm from the anal verge. Biopsies revealed cryptitis, crypt abscesses, crypt architecture distortion and Paneth cell metaplasia. The patient underwent laparoscopic left colectomy. Results The rectosigmoid colon specimen is 18.0 cm in length and 6.0 cm in diameter. There was a 7.5 cm segment with numerous polyps. Multiple diverticula with diverticulitis were also identified in this region. The rest of the colon was unremarkable. Microscopic examination revealed numerous IPs and multiple diverticulitis. No evidence of IBD was identified. Conclusion To our knowledge, this is the first time that segmental and diffuse IPs are described with associated diverticulitis in the absence of IBD. The pathogenesis of IPs in non-inflammatory bowel disease is not well described. Previously, it was reported that diverticulosis and subsequent diverticulitis has no significant impact on the development of IPs, and IPs may arise independent of location and time of diverticulitis. Sporadic IPs may also appear without any underlying pathology. In the current case, there were multiple diverticula and diffuse diverticulitis, which may have contributed to the diffuse IPs. Further clinical inquiries revealed no clinical signs and symptoms of IBD.

Diagnostic interobserver variability in Crohn's disease- and ulcerative colitis-associated dysplasia: a multicenter digital survey from the IG-IBD Pathologists Group.

Crohn's disease (CD) and ulcerative colitis, two forms of inflammatory bowel disease (IBD), are chronic and relapsing conditions of the gastrointestinal tract both characterized by long lasting chronic inflammation and increased risk of dysplasia and colorectal cancer (CRC). The aim of our study was to evaluate the interobserver agreement about IBD-associated dysplasia among pathologists belonging to the Italian Group for Inflammatory Bowel Diseases (IG-IBD P). The present multicenter survey was performed using telepathology, supported by an open source E-learning platform. Biopsy specimens from 30 colonoscopies and from 20 patients were included. The glass slides of any case, including clinical and endoscopic data, were digitalized and uploaded on the E-learning platform. All the digital slides were grouped in 54 diagnostic "blocks". Blinded histopathological evaluation on all the digital slides was performed by 20 gastrointestinal pathologists. Closed-ended questions about (1) the occurrence of IBD; (2) the classification of IBD (as UC or CD); (3) the presence of active versus quiescent disease; (4) the presence of dysplasia; (5) the possible association of dysplasia with the sites of disease (dysplasia-associated lesion or mass-DALM vs adenoma-like mass-ALM); (6) the grading of dysplasia according to the ECCO guidelines (negative, indefinite, low grade, high grade categories) and (7) the presence of associated serrated features, were proposed in each case. Inter-observer agreement was evaluated by mean agreement percentage and kappa statistic, when suitable. The diagnosis of IBD was confirmed in 19 of 20 patients, 17 of 19 being classified as UC, 2 as CD. The mean interobserver agreement percentages about (1) the evidence of IBD, (2) the presence of either UC or CD and (3) the activity grading resulted to be 80%, 69% and 86%, respectively. Dysplasia was detected in 8/20 patients, with moderate agreement between pathologists (mean 72%, k 0.48). Particularly, low grade dysplasia was found in 13 biopsies (combined k 0.38), whereas high grade dysplasia in 8 (combined k 0.47). When the endoscopic and histopathological data were combined, features consistent with DALM were found in 6 of 20 patients with low grade dysplasia and those consistent with ALM in 2 patients with low grade dysplasia in a single biopsy (mean agreement: 86%). An associated serrated pattern was discovered in 4 patients (7 biopsies). Our study showed moderate interobserver agreement about the histopathological detection and classification of IBD-associated dysplasia. Further efforts should be undertaken to integrate the histopathological data with both the ancillary tests and molecular investigations.

High Incidence of Early-Onset Colon Cancer in Ethiopia: Clinical and Therapeutic Evaluation With Genetic Mutational Analyses

PURPOSE Colon cancer has been reported to occur early in certain African regions, but our understanding of the genetic modifications that lead to early disease is incomplete. We aimed to study cases of early colon cancer and the genetic modifications leading to these tumors in Ethiopia. METHODS We evaluated all colon masses detected between 2015 and 2018 at Black Lion Hospital, Addis Ababa, Ethiopia. Clinical, endoscopic, and pathology descriptions were assessed for all cases in patients age 30 years or younger. Subsets of pathology block tissues were evaluated for genetic modifications via multiplex ligation-dependent probe amplification. RESULTS We identified a total of 38 cases of colon cancer in patients age 30 years or younger. These represented 13% of all cases of colon cancer in the 3-year period. Median age was 27 years (interquartile range, 27-30 years), and 50% of individuals were female. None of the cases reported a family history of colon cancer or had evidence of inflammatory bowel disease. The most common presenting symptom was rectal bleeding (57%), followed by a change in bowel habit (22%). All samples but one were identified as adenocarcinoma, 78% were confined to the rectum, and 65% had distant metastasis or locally advanced disease at the time of diagnosis. Longer duration of symptoms correlated with the presence of metastasis on diagnosis ( P = .035). Surgery (23%) and chemotherapy (15%) were the most frequently used treatments. We performed genetic analysis of biopsy tissue in a subset of 3 individuals: a 21-year-old male showed decreased copies of APC, an increase in K-ras, V600F mutation in BRAF, and a decrease in MSH2 and MLH1; a 21-year-old female showed duplication of exon 4 APC, a decrease in K-ras, and decreased copies of MSH-2; and a 30-year-old female showed decreased copies of APC, decreased copies of K-ras and BRAF, and decreased copies of MSH2 and MLH1. CONCLUSION We report a high incidence of early colon cancer in Ethiopia in patients with no family history or inflammatory bowel disease. Genetic analyses in a subset of patients showed APC and K-ras alterations as well as modifications of the mismatch repair pathway.

3041 Eosinophilic Colitis: A Rare Entity

INTRODUCTION: Eosinophilic colitis (EC) is a rare entity characterized by abnormal infiltration of colon mucosa by eosinophils without evidence of any secondary causes. Presentation may include asymptomatic state, chronic diarrhea, abdominal pain, rectal bleed, bowel obstruction or ascites. We present two cases of EC with very different presentations requiring minimal or no therapy. CASE DESCRIPTION/METHODS: CASE 1: 57 year old Filipino male presented with abdominal pain and new onset ascites. Paracentesis revealed elevated SAAG suggestive of portal hypertension. Imaging studies were negative for cirrhosis. Negative liver workup for chronic liver disease. Lab studies revealed microcytic anemia and peripheral eosinophilia of 10%. No eosinophilia noted in ascitic fluid. EGD showed LA Grade C esophagitis. Colonoscopy showed multiple polyps which were removed. Pathology from polyps showed markedly increased eosinophil infiltrate in mucosa and submucosa. There was no evidence of inflammatory bowel disease, Stool studies were negative for infectious etiology. No incriminating medications were found which could lead to above finding. The patient was treated with omeprazole and diuretics with complete resolution of symptoms. CASE 2: 27 year old female presented with chronic intermittent abdominal pain, nausea and diarrhea for 2 years. Her only medications were birth control pills. She had normal blood counts, electrolytes, liver, and renal function. Stool studies were negative for any infectious etiology. She had normal fecal fat and electrolytes. EGD and colonoscopy were unremarkable. Biopsies were negative for celiac disease, Helicobacter and eosinophilic esophagitis. Random colon biopsies showed benign colon mucosa with focal infiltration of colonic mucosa with eosinophils suggestive of eosinophilic colitis. There was no peripheral eosinophilia. Patient was started on probiotics with prompt resolution of symptoms. DISCUSSION: EC is a rare condition, included in the group of eosinophilic gastrointestinal disorders, characterized by eosinophil infiltration of colonic mucosa in the absence of any food allergies, parasitic/helminthic infections, drugs, IBD, celiac and autoimmune diseases. The treatment options include dietary modifications, steroids, mesalamine, immunomodulatory agents, fecal microbiota transplant and surgery. The evidence for most of treatment options is limited to case reports. One of our patients required no specific therapy while other one was treated successfully with probiotics.

163 High Incidence of Early Onset Colon Cancer in Ethiopia: Clinical and Therapeutic Evaluation With Genetic Mutational Analyses

INTRODUCTION: Colon cancer has been reported to occur early in certain African regions, but the understanding of genetic modifications leading to early disease is incomplete. We aimed to study cases of early colon cancer and genetic modifications leading to these tumors in Ethiopia. METHODS: We evaluated all colon masses detected between 2015 and 2018 at Black Lion Hospital, Addis Ababa. Clinical, endoscopic and pathology descriptions were assessed for all cases in 30-year-olds or younger. Subsets of pathology block-tissues were evaluated for genetic modifications via Multiplex Ligation-dependent Probe Amplification. RESULTS: A total of 38 cases of colon cancer ages 30 or earlier were identified. These represented 13% of all cases of colon cancer in the 3-year period. The median age was 27 years (IQR 27–30), and 50% of individuals were female. None of the cases reported a family history of colon cancer or had evidence of inflammatory bowel disease (IBD). The most common presenting symptom was rectal bleeding (57%) followed by a change in bowel habit (22%). All but one sample were identified as adenocarcinoma, 78% were confined to the rectum, and 65% had distant metastasis or locally advanced disease at the time of diagnosis. Longer duration of symptoms correlated with the presence of metastasis on diagnosis (P = 0.035). Surgery (23%) and chemotherapy (15%) were the most frequently used treatments. We performed genetic analysis of biopsy tissue in a subset of 3 individuals: a) 21 y/o-male showed decrease copies of APC, increase in K-ras, v600f mutation in BRAF and decrease in MSH2 and MLH1; b) 21 y/o-female showed duplication of exon 4 APC, decrease in K-ras and decreased copies of MSH-2; c) 30 y/o-female showed decreased copies of APC, decreased copies of K-ras and BRAF and decreased copies of MSH2 and MLH1. CONCLUSION: We report a high incidence of early colon cancer in Ethiopia with no family history or IBD. Most patients presented with rectal bleeding. Genetic analyses in a subset of patients showed APC and K-ras alterations as well as modifications of mismatch repair pathways.

The Influence of Bowel Preparation on ADC Measurements: Comparison between Conventional DWI and DWIBS Sequences.

Background and objectives: The aim of the study was to assess whether there were differences between apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI) and diffusion-weighted imaging with background body signal suppression (DWIBS) sequences in non-prepared and prepared bowels before and after preparation with an enteric hyperosmolar agent, to assess whether ADC measurements have the potential to avoid bowel preparation and whether ADC-DWIBS has advantages over ADC-DWI. Materials and Methods: 106 adult patients without evidence of inflammatory bowel disease (IBD) underwent magnetic resonance (MR) enterography before and after bowel preparation. ADC-DWI and ADC-DWIBS values were measured in the intestinal and colonic walls demonstrating high signal intensity (SI) at DWI tracking images of b = 800 s/mm2 before and after preparation. Results: There were significant difference (p < 0.0001) in both ADC-DWI and ADC-DWIBS results between non-prepared and prepared jejunum for DWI being 1.09 × 10−3 mm2/s and 1.76 × 10−3 mm2/s, respectively, and for DWIBS being 0.91 × 10−3 mm2/s and 1.75 × 10−3 mm2/s, respectively. Both ADC-DWI and DWIBS also showed significant difference between non-prepared and prepared colon (p < 0.0001), with DWI values 1.41 × 10−3 mm2/s and 2.13 × 10−3 mm2/s, and DWIBS—1.01 × 10−3 mm2/s and 2.04 × 10−3 mm2/s, respectively. No significant difference between ADC-DWI and ADC-DWIBS was found in prepared jejunum (p = 0.84) and prepared colon (p = 0.58), whereas a significant difference was found in non-prepared jejunum and non-prepared colon (p = 0.0001 in both samples). Conclusions: ADC between DWI and DWIBS does not differ in prepared bowel walls but demonstrates a difference in non-prepared bowel. ADC in non-prepared bowel is lower than in prepared bowel and possible overlap with the ADC range of IBD is possible in non-prepared bowel. ADC-DWIBS has no advantage over ADC-DWI in regard to IBD assessment.

Colonoscopic Findings of Patients with Lower Gastrointestinal Bleeding in Erbil City

Background and objectives: Rectal bleeding is a frequent symptom in young people and often over- investigated.Rectal bleeding is defined as bleeding from lower gastrointestinal tract, which means bleeding from a place distal to ligament of Treitz. This study was conducted to determine the frequency of different causes of rectal bleeding in young patients. Methods: Four hundred and seventy patients with rectal bleeding were selected in out-patient department were referred to gastroenterology units of Hawler and Rizgary Hospital in Erbil. Patients with suspected upper GI source of bleeding excluded from the study. All patients were subjected to colonoscopy after preparation of the gut and the findings were recorded. When it was necessary, biopsy samples were also taken. Diagnosis was based on colonoscop- ic findings. Results: The total number of patients was 470. Their mean age + SD were 31.96 + 7.65 years, the median was 32 years, ranging from 12 to 46 years, more than one third of patients had hemorrhoids, either alone (35.7%), or with other finding, (45%) of patients had hemorrhoid with or without other diseases, (8.3%) had inflammatory bowel disease and colorectal tumor (4.7%), also 21.3% of patients found to be normal. Conclusions:Haemorrhoids were the main cause of bleeding per rectum, followed by evidence of inflammatory bowel disease. The incidence of colorectal tumor was low (4.7%). Though most findings were benign, colonoscopy should be strongly considered for this patient group with non urgent rectal bleeding.

Immunotherapy-Induced Colitis with Perforation Treated with Infliximab Postoperatively

The advent of checkpoint-inhibitor therapy in medical oncology has led to an increase in the number of patients hospitalized for severe colitis. Colitis commonly presents approximately 6 weeks after beginning immunotherapy with the incidence being higher for patients treated with CTLA-4 inhibitors as compared to treatment with anti-PD-1/PD-L1 antibodies. Severe colitis has been reported in approximately 5% of patients treated with ipilimumab (CTLA-4 inhibitor). Standard management for those with severe colitis includes administration of systemic corticosteroids with the reservation of infliximab if there has been no improvement. Rarely, colitis can result in bowel perforation requiring surgical intervention with colectomy/colostomy. Here we present a case of severe colitis with bowel perforation requiring treatment with infliximab. A 72-year-old male with advanced metastatic melanoma began treatment with ipilimumab and nivolumab (PD-1 inhibitor). After completing his first cycle he developed hematochezia. He was hospitalized and started on methylprednisolone then tapered to prednisone with improvement in his symptoms. Following discharge, he was to discontinue treatment with ipilimumab and resume nivolumab. However, prior to resuming therapy, he developed recurrent colitis requiring repeat treatment with prednisone. His symptoms worsened with severe right upper quadrant abdominal pain. He was again started on methylprednisolone. CT imaging revealed pancolitis and pneumoperitoneum due to perforation of the transverse colon. He underwent emergent laparotomy with extended right hemicolectomy and end ileostomy but continued to have hematochezia after surgery. He was felt to be at high risk for recurrence given the extent and severity of his colitis. IV Infliximab 5 mg/kg was administered with significant clinical improvement. Immunotherapy-induced colitis with bowel perforation remains a rare but life-threatening adverse reaction to checkpoint-inhibitor therapy. Postoperative treatment with infliximab for Crohn's disease has been found to be safe when administered within 4 weeks of intestinal resection; however, there remains limited data to support administration of infliximab following bowel perforation due to immunotherapy-induced colitis. This case illustrates a severe adverse reaction to checkpoint-inhibitor therapy and the necessity to further evaluate the role of infliximab in post-operative patients who develop colitis with bowel perforation.1623 Figure 1. CT abdomen/pelvis with evidence of colitis and site of perforation