DOP17 AZD4205, a potent, GI tract-enriched, JAK1-selective inhibitor for treatment of inflammatory bowel disease (IBD)

2019 ◽  
Vol 13 (Supplement_1) ◽  
pp. S036-S037 ◽  
Author(s):  
M Wang ◽  
T John ◽  
L Zhang ◽  
L Zhu ◽  
Y Xu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Selective Inhibitor ◽  
Gi Tract ◽  
Inflammatory Bowel

Inflammatory bowel disease

2018 ◽  
Author(s):  
Satish Keshav ◽  
Alexandra Kent
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Age Of Onset ◽  
Anal Verge ◽  
Age At Onset ◽  
Mucosal Inflammation ◽  
Gi Tract ◽  
Disease Extent ◽  
Inflammatory Bowel ◽  
Different Characteristics

Inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn’s disease (CD). Both conditions cause chronic relapsing inflammation in the gastrointestinal (GI) tract, but have different characteristics. UC causes diffuse mucosal inflammation limited to the colon, extending proximally from the anal verge, with the rectum involved in 95% of patients. UC is described in terms of the disease extent: proctitis (confined to the rectum), proctosigmoiditis (disease confined to the recto-sigmoid colon), distal disease (distal to the splenic flexure), and pan-colitis (the entire large intestine). The extent of disease can change, with proximal extension seen in approximately a third of patients with proctitis, although there is great variation between studies. CD causes inflammation that can affect the entire thickness of the wall of the intestine, and is not confined to the mucosa. CD can affect any part of the GI tract. The terminal ileum is affected in approximately 80% of cases, the colon in approximately 60% of cases, and the rectum and perianal region in approximately 40% of cases. CD is classified by location (ileal, colonic, ileocolonic, upper GI tract), by the presence of stricturing or penetrating disease, and by the age of onset (before or after the age of 40). Penetrating disease refers to the development of fistulae, which can lead to complications such as abscesses or perforations. An earlier age at onset is associated with more complicated disease. The diagnosis of UC or CD is established through a combination of clinical, endoscopic, radiological, and histological criteria rather than by any single modality. Occasionally, it is not possible to establish an unequivocal diagnosis of CD or UC in IBD, and a third category, accounting for nearly 10% of cases, is used, termed IBD unclassified.

Indeterminate Dendritic Cell Tumor (IDCT) of GI Tract, Lymph Node and Spleen Masquerading as Refractory Inflammatory Bowel Disease

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S108-S108
Author(s):  
W Huang ◽  
M G Bayerl
Keyword(s):  
Inflammatory Bowel Disease ◽  
Lymph Node ◽  
Dendritic Cell ◽  
Tumor Cells ◽  
Bowel Disease ◽  
Langerhans Cells ◽  
Cell Tumor ◽  
Gi Tract ◽  
Medical Treatments ◽  
Inflammatory Bowel

Abstract Introduction/Objective Indeterminate dendritic cell tumor (IDCT) is an extremely rare neoplasm, most frequently presenting in skin with cells resembling precursors to Langerhans cells. We report an exceptional case of IDCT occurring in GI tract, spleen, and lymph nodes of a 66-year-old lady, mimicking inflammatory bowel disease (IBD). Methods Four years prior to the diagnosis of IDCT, she was diagnosed with ulcerative colitis (UC) based on bloody diarrhea and pan-colitis. Her colitis became refractory to medical treatments and she developed pancytopenia, splenomegaly and abdominal lymphadenopathy. A FNA of abdominal lymph node and a colonoscopic biopsy both showed non-necrotizing granulomas, which along with her multiple oral ulcers suggested Crohn’s disease. Due to failure to medical treatments, she underwent proctocolectomy and ileostomy, followed later by subtotal colectomy with excision of a splenule and lymph nodes. Results All specimens from the final operation showed involvement by IDCT characterized by polygonal cells with abundant eosinophilic cytoplasm, oval nuclei with occasional nuclear grooves, open chromatin and eosinophilic nucleoli. By immunohistochemistry, the tumor cells expressed S100, CD1a, cyclin D1, BRAFV600E. Langerin staining was observed in <5% of cells, suggesting partial differentiation of tumor cells (frequently seen in IDCT) vs. reactive Langerhans cells. No overt cytological atypia and no necrosis were observed. Eosinophils, neutrophils, lymphocytes and plasma cells were sparse. There was no emperioloperesis. The colon showed multifocal active and chronic inflammation and ulcerations associated with the IDCT infiltrate. These specimens were diagnostic of IDCT. Conclusion Absence Langerin in the majority of cells excluded the possibility of Langerhans cell histiocytosis. The presence of CD1a and absence of bone involvement excluded the possibility of Erdheim-Chester disease. Retrospectively, it appears that the patient’s symptoms were due to IDCT rather than IBD. The clinical course of IDCT is highly variable, but the BRAF mutation offers a promising new therapeutic target for this patient.

Common Etiologies and Clinical Significance of Gastric Intraepithelial Lymphocytosis

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S61-S62
Author(s):  
Sunjida Ahmed ◽  
Ruliang Xu
Keyword(s):  
Inflammatory Bowel Disease ◽  
Morbid Obesity ◽  
Celiac Disease ◽  
Bowel Disease ◽  
Intraepithelial Lymphocytes ◽  
Gi Tract ◽  
Inflammatory Bowel ◽  
H Pylori ◽  
Intraepithelial Lymphocytosis

Abstract Background Increased intraepithelial lymphocytes or intraepithelial lymphocytosis (IEL) in the upper gastrointestinal (GI) tract is a response to various mucosal injury. However, the frequency of gastric IEL in GI tract biopsy is not well documented, and the etiologies of gastric IEL are yet to be defined. Methods Cases with a diagnosis of “intraepithelial lymphocytosis” and “intraepithelial lymphocytes” were retrieved from 25,074 GI biopsies and 8,921 partial gastrectomies in our departmental database (Powerpath) for a 1-year period. The diagnosis of IEL was confirmed by the report and/or slide review. Possible etiology or causes of gastric IEL were investigated by correlation with clinical information from LIS (EPIC). Results A total of 694 cases with IEL were identified from 33,995 GI tract specimens (biopsy and resection). Among 694 cases, 34 (4.89%) were gastric biopsy and resection cases with IEL, whereas 561 (80.8%), 37 (5.3%), and 62 (8.9%) were duodenal, esophageal, and colonic specimens, respectively. Thirty-four gastric cases with IEL were closely associated with morbid obesity (8, 23.5%), H pylori infection (8, 23.5%), celiac disease (5, 14.7%), lymphocytic gastritis (5, 14.7%), nonspecific gastritis (4, 11.4%), inflammatory bowel disease (3, 8.8%), and gastroesophageal reflux disease (1, 1.9%). Seventeen of 34 (50%) cases had IEL in both gastric and duodenal mucosa. Those 17 cases with gastroduodenal IEL had morbid obesity (n = 5), celiac disease (n = 5), lymphocytic colitis (n = 2), inflammatory bowel disease (n = 2), H pylori gastritis (n = 2), and nonspecific gastritis (n = 1). Five patients with a diagnosis of lymphocytic gastritis were treated with a protein pump inhibitor after pathologic diagnosis. Among them, 4 had a followed-up endoscopy in 12 months, and 3 of them showed persistent IEL in a follow-up biopsy. Conclusion Gastric IEL is less common than duodenal IEL. It is associated with a broad differential diagnosis. Follow-up biopsy may be necessary for some types of gastric IEL. Persistent IEL in follow-up biopsy may be suggestive of a different etiology or requires different treatment strategy.

scholarly journals From the inside out: the gut microbiome and inflammatory bowel disease

2017 ◽  
Vol 39 (4) ◽  
pp. 12-15
Author(s):  
Monica Viladomiu ◽  
Randy S. Longman
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Potential Contribution ◽  
Gi Tract ◽  
Technological Advances ◽  
Chronic Inflammatory Condition ◽  
Inflammatory Bowel ◽  
The Impact

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal (GI) tract with two main clinical types: Crohn's disease, which can affect any part of the GI tract, and ulcerative colitis (UC), which is limited to the colon. While early research focused primarily on the immune dysregulation and genetic susceptibilities associated with IBD, recent groundbreaking technological advances have allowed the investigation of additional factors, including diet and microbial exposures, in the onset and severity of disease. Advances in high-throughput microbial sequencing, anaerobic bacterial culturing techniques and generating germ-free mouse models have revolutionized our understanding of the microbial species associated with inflammation. While the long-standing clinical efficacy of antibiotics or surgery for Crohn's disease highlights the potential contribution of the socalled ‘IBD microbiome’ to inflammation, recent seminal studies revealed the impact of IBD-derived gut microbiota on host mucosal and systemic inflammation. This mechanistic understanding of how our ‘microbial organ’ functionally impacts both mucosal and systemic inflammatory pathways will help drive novel diagnostic and therapeutic approaches for IBD.

scholarly journals Pituitary adenylate cyclase activating peptide-27 – like immunoreactive nerve fibers in the mucosal layer of canine gastrointestinal tract in physiology and during inflammatory bowel disease

2013 ◽  
Vol 57 (3) ◽  
pp. 375-380 ◽  
Author(s):  
Sławomir Gonkowski ◽  
Andrzej Rychlik ◽  
Jarosław Całka
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adenylate Cyclase ◽  
Bowel Disease ◽  
Nerve Fibers ◽  
Gi Tract ◽  
Pituitary Adenylate Cyclase ◽  
Mucosal Layer ◽  
Inflammatory Bowel ◽  
Descending Colon ◽  
Labelling Immunofluorescence

Abstract Changes in the density of mucosal pituitary adenylate cyclase activating peptide-27 -like immunoreactive (PACAP-27 - LI) nerve fibers within various parts of the canine gastrointestinal (GI) tract during inflammatory bowel disease (IBD) were investigated. The distribution of nerves were studied, using a single-labelling immunofluorescence technique, in the mucosal layer of canine stomach, duodenum, jejunum, and descending colon. Canine IBD caused an increase in the density of PACAP- 27-LI mucosal nerves in all studied parts of GI tract. The results suggest that PACAP in the nervous system may be involved in pathological processes during IBD.

Review of Inflammatory Bowel Disease

2016 ◽  
Author(s):  
Joshua Guttman ◽  
Frederick Davis
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn Disease ◽  
Bowel Disease ◽  
Supportive Therapy ◽  
Signs And Symptoms ◽  
Aminosalicylic Acid ◽  
Gi Tract ◽  
Hospital Patients ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is an inflammatory condition of the gastrointestinal (GI) tract made up of ulcerative colitis (UC) and Crohn disease (CD). These diseases are differentiated based on the location in the GI tract and findings on colonoscopy and biopsy. Management in the emergency department is similar for these two conditions. Patients presenting with exacerbations of known IBD should be classified according to severity and managed accordingly. Mild to moderate disease will require only a limited workup consisting of testing for anemia and electrolyte abnormalities. These patients may be discharged with a 5-aminosalicylic acid (5-ASA) agent, or if the condition is refractory to 5-ASA, then with oral budesonide. Severe or fulminant disease will need intravenous hydration, intravenous corticosteroids, computed tomography (CT) to assess for intestinal complications, and admission to the hospital. Patients with abscesses, colitis, or ileitis on CT will need antibiotics. Additionally, patients should be evaluated for both intestinal complications, such as strictures and fistulas, and extraintestinal manifestations, the majority of which are dermatologic and ophthalmologic. Patients with fulminant complications, toxic megacolon and intestinal perforation, should receive intravenous antibiotics, hydration, and immediate surgical consultation. Patients presenting with signs and symptoms of IBD but without a known diagnosis should receive supportive therapy. If discharged, they should be referred to a gastroenterologist for colonoscopy to make an appropriate diagnosis and to initiate therapy.   Key words: Inflammatory bowel disease (IBD), gastrointestinal (GI) tract, ulcerative colitis (UC), Crohn disease (CD), colonoscopy, fulminant complications   This review contains highly rendered 5 figures, 5 tables, and 30 references.

scholarly journals Video Capsule Retention in Inflammatory Bowel Disease: An Unusual Presentation and Discussion of Retrieval Methods

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
R. Goel ◽  
J. Hardman ◽  
M. Gulati ◽  
J. O'Donohue
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Ileoanal Pouch ◽  
Atypical Presentation ◽  
Potential Complication ◽  
Gi Tract ◽  
Ileal Stricture ◽  
Inflammatory Bowel ◽  
Capsule Retention ◽  
Endoscopic Methods

Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation in the gastrointestinal (GI) tract. Video capsule endoscopy (VCE) is widely used to investigate the small bowel, and capsule retention is the most serious potential complication. Endoscopic and surgical management has been reported, but in the absence of bowel obstruction, there is little consensus as to which should be employed. In this case report, we describe a patient who was investigated with VCE for weight loss and anaemia. He had previously undergone colectomy with ileoanal pouch formation for ulcerative colitis (UC). Capsule retention occurred at an ileal stricture and he was subsequently diagnosed with Crohn's disease (CD). We describe his medical management and successful capsule retrieval using endoscopic methods. This case also highlights the importance of screening for intestinal strictures in an atypical presentation of UC following colectomy.

Sign in / Sign up

Export Citation Format

Share Document