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Cell Oct 2020A mysterious feature of Crohn's disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the...
A mysterious feature of Crohn's disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.
Topics: Adipose Tissue; Animals; Bacterial Translocation; Biodiversity; Biomarkers; Cell Polarity; Cells, Cultured; Colitis, Ulcerative; Crohn Disease; Gastrointestinal Microbiome; Gene Expression Regulation; Germ-Free Life; Humans; Ileum; Lipopolysaccharides; Macrophages; Mesentery; Metagenome; Metagenomics; Mice; Mice, Inbred C57BL; Phenotype; RNA, Ribosomal, 16S; Stem Cells
PubMed: 32991841
DOI: 10.1016/j.cell.2020.09.009 -
Saudi Journal of Gastroenterology :... 2010Meckel's diverticulum is a true intestinal diverticulum that results from the failure of the vitelline duct to obliterate during the fifth week of fetal development. In... (Review)
Review
Meckel's diverticulum is a true intestinal diverticulum that results from the failure of the vitelline duct to obliterate during the fifth week of fetal development. In about 50% cases, it contains ectopic or heterotopic tissue which can be the cause of complications. A systematic review of literature was undertaken to study the history, incidence, embryoanatomy, clinical presentation, complication and management of Meckel's diverticulum. Although Meckel's diverticulum is the most common congenital abnormality of the gastrointestinal tract, it is often difficult to diagnose. It may remain asymptomatic or it may mimic disorders such as Crohn's disease, appendicitis and peptic ulcer disease.
Topics: Diagnosis, Differential; Humans; Meckel Diverticulum
PubMed: 20065566
DOI: 10.4103/1319-3767.58760 -
Journal of Crohn's & Colitis Feb 2018Restorative proctocolectomy with ileal pouch-anal anastomosis removes the diseased tissue in ulcerative colitis but also allows gastrointestinal continuity and... (Review)
Review
BACKGROUND
Restorative proctocolectomy with ileal pouch-anal anastomosis removes the diseased tissue in ulcerative colitis but also allows gastrointestinal continuity and stoma-free living. Pouch strictures are a complication with a reported incidence of 5-38%. The three areas where pouch strictures occur are in the pouch inlet, mid-pouch and pouch-anal anastomosis.
AIM
To undertake a systematic review of the literature and to identify management strategies available for pouch-anal, mid-pouch and pre-pouch ileal strictures and their outcomes.
METHODS
A computer-assisted search of the online bibliographic databases MEDLINE and EMBASE limited to 1966 to February 2016 was performed. Randomized controlled trials, cohort studies, observational studies and case reports were considered. Those where data could not be extracted were excluded.
RESULTS
Twenty-two articles were considered eligible. Pouch-anal strictures have been initially managed using predominately dilators which include bougie and Hegar dilators with various surgical procedures advocated when initial dilatation fails. Mid-pouch strictures are relatively unstudied with both medical, endoscopic and surgical management reported as successful. Pouch inlet strictures can be safely managed using a combined medical and endoscopic approach.
CONCLUSION
The limited evidence available suggests that pouch-anal strictures are best treated in a stepwise fashion with initial treatment to include digital or instrumental dilatation followed by surgical revision or resection. Management of mid-pouch strictures requires a combination of medical, endoscopic and surgical management. Pouch inlet strictures are best managed using a combined medical and endoscopic approach. Future studies should compare different treatment modalities on separate stricture locations to enable an evidenced-based treatment algorithm.
Topics: Colonic Pouches; Constriction, Pathologic; Digestive System Surgical Procedures; Dilatation; Endoscopy, Gastrointestinal; Humans; Ileum
PubMed: 29155985
DOI: 10.1093/ecco-jcc/jjx151 -
World Journal of Gastroenterology Sep 2008Crohn's disease may principally involve the whole gastrointestinal tract. Most commonly, the inflammation occurs in the small intestine and/or in the colon with stable... (Review)
Review
Crohn's disease may principally involve the whole gastrointestinal tract. Most commonly, the inflammation occurs in the small intestine and/or in the colon with stable disease location over the years. The pathogenesis of both disease phenotypes is complex, the likely primary defect lies in the innate rather than adaptive immunity, particularly in the chemical antimicrobial barrier of the mucosa. Crohn's ileitis is associated with a reduced expression of the Wnt signalling pathway transcription factor T-cell factor 4 (TCF4), which is regulating Paneth cell differentiation. As a result, the alpha-defensins and principal Paneth cell products HD5 and HD6 are deficiently expressed in ileal disease, independent of current inflammation. In contrast, Crohn's colitis is typically associated with an impaired induction of the beta-defensins HBD2 and HBD3 caused by fewer gene copy numbers in the gene locus of the beta-defensins on chromosome 8. This ileal and colonic defect in innate defence mediated by a deficiency of the protective alpha- and beta-defensins may enable the luminal microbes to invade the mucosa and trigger the inflammation. A better understanding of the exact molecular mechanisms behind ileal and colonic Crohn's disease may give rise to new therapeutic strategies based on a stimulation of the protective innate immune system.
Topics: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Colitis, Ulcerative; Colon; Crohn Disease; DNA-Binding Proteins; Humans; Ileum; Immunity, Innate; Immunity, Mucosal; Paneth Cells; Stem Cells; Transcription Factor 4; Transcription Factors; alpha-Defensins; beta-Defensins
PubMed: 18810765
DOI: 10.3748/wjg.14.5499 -
Gut Aug 1964These three papers present studies on gastrin. The first paper describes a method of biological assay using the rat. The second paper demonstrates that the highest...
These three papers present studies on gastrin. The first paper describes a method of biological assay using the rat. The second paper demonstrates that the highest concentration of gastrin-like activity occurs in the antral mucosa, with a clear gradient of concentration of activity down the gut. However, it is to be noted that the total amount of extractable activity is greatest in the duodenum, although the concentration there is less than in the antrum. No activity was detected in the pancreas. The third paper studies the contents of gastrin-like activity in patients with duodenal ulcer and demonstrates higher figures when stenosis is present. Patients with benign gastric ulcer and carcinomata showed results equal to or greater than in those with the average uncomplicated duodenal ulcer. It was noted that two patients with dilated antra both had very low total gastrin-like activity. There was no correlation between total activity and maximal histamine-stimulated output of acid. There was, however, a positive correlation between the insulin-stimulated acid secretion and the total gastrin-like activity in the cases of uncomplicated duodenal ulcers. The clinical studies are still tentative in view of the several variables present, but it seems likely that they will in due course clarify the role of gastrin in the ulcer problem.
Topics: Biological Assay; Biomedical Research; Colon; Duodenal Ulcer; Duodenum; Freeze Drying; Gastrectomy; Gastric Mucosa; Gastrins; Histology; Humans; Ileum; Insulin; Jejunum; Pancreas; Rats; Research; Statistics as Topic; Stomach Neoplasms; Stomach Ulcer; Zollinger-Ellison Syndrome
PubMed: 14209916
DOI: 10.1136/gut.5.4.327 -
Journal of Visceral Surgery Sep 2014Restorative proctocolectomy with ileal pouch-anal anastomosis has become the most commonly used procedure for elective treatment of patients with ulcerative colitis and... (Comparative Study)
Comparative Study Review
Restorative proctocolectomy with ileal pouch-anal anastomosis has become the most commonly used procedure for elective treatment of patients with ulcerative colitis and familial adenomatous polyposis. Since its original description, the procedure has been modified in order to obtain optimal functional results with low morbidity and mortality, and yet provide a cure for the disease. In this review of the literature of restorative proctocolectomy with ileal pouch-anal anastomosis, we discuss these technical modifications, limiting our discussion to the current points of controversy. The current "hot topics" for debate are: indications for ileal pouch-anal or ileo-rectal anastomosis, indications for pouch surgery in the elderly, indeterminate colitis and Crohn's disease, the place of the laparoscopic approach, transanal mucosectomy with hand-sewn anastomosis vs. the double-stapled technique, the use of diverting ileostomy and the issue of the best route for delivery of pregnant women. Longer follow-up of patients and increased knowledge and experience with pouch surgery, coupled with ongoing prospective evaluation of the procedure are required to settle these issues.
Topics: Adenomatous Polyposis Coli; Aged; Anal Canal; Anastomosis, Surgical; Colitis, Ulcerative; Colonic Pouches; Elective Surgical Procedures; Female; Humans; Ileum; Male; Patient Selection; Postoperative Complications; Pregnancy; Proctocolectomy, Restorative; Prognosis; Quality Control; Risk Assessment; Surgical Stapling; Treatment Outcome
PubMed: 24999229
DOI: 10.1016/j.jviscsurg.2014.05.004 -
The American Journal of Gastroenterology Mar 2017Distinguishing intestinal tuberculosis (ITB) from Crohn's disease (CD) is difficult, although studies have reported clinical, endoscopic, imaging, and laboratory... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Distinguishing intestinal tuberculosis (ITB) from Crohn's disease (CD) is difficult, although studies have reported clinical, endoscopic, imaging, and laboratory findings that help to differentiate these two diseases. We aimed to produce estimates of the predictive power of these findings and construct a comprehensive model to predict the probability of ITB vs. CD.
METHODS
A systematic literature search for studies differentiating ITB from CD was conducted in MEDLINE, PUBMED, and EMBASE from inception until September 2015. Fifty-five distinct meta-analyses were performed to estimate the odds ratio of each predictive finding. Estimates with a significant difference between CD and ITB and low to moderate heterogeneity (I<50%) were incorporated into a Bayesian prediction model incorporating the local pretest probability.
RESULTS
Thirty-eight studies comprising 2,117 CD and 1,589 ITB patients were included in the analyses. Findings in the model that significantly favored CD included male gender, hematochezia, perianal disease, intestinal obstruction, and extraintestinal manifestations; endoscopic findings of longitudinal ulcers, cobblestone appearance, luminal stricture, mucosal bridge, and rectal involvement; pathological findings of focally enhanced colitis; and computed tomographic enterography (CTE) findings of asymmetrical wall thickening, intestinal wall stratification, comb sign, and fibrofatty proliferation. Findings that significantly favored ITB included fever, night sweats, lung involvement, and ascites; endoscopic findings of transverse ulcers, patulous ileocecal valve, and cecal involvement; pathological findings of confluent or submucosal granulomas, lymphocyte cuffing, and ulcers lined by histiocytes; a CTE finding of short segmental involvement; and a positive interferon-γ release assay. The model was validated by gender, clinical manifestations, endoscopic, and pathological findings in 49 patients (27 CD, 22 ITB). The sensitivity, specificity, and accuracy for diagnosis of ITB were 90.9%, 92.6%, and 91.8%, respectively.
CONCLUSIONS
A Bayesian model based on the meta-analytic results is presented to estimate the probability of ITB and CD calibrated to local prevalence. This model can be applied to patients using a publicly available web application.
Topics: Ascites; Bayes Theorem; Constriction, Pathologic; Crohn Disease; Diagnosis, Differential; Endoscopy, Digestive System; Fever; Gastrointestinal Hemorrhage; Granuloma; Humans; Ileocecal Valve; Interferon-gamma Release Tests; Intestinal Obstruction; Models, Theoretical; Rectum; Sensitivity and Specificity; Sex Factors; Sweating; Tomography, X-Ray Computed; Tuberculosis, Gastrointestinal; Ulcer
PubMed: 28045023
DOI: 10.1038/ajg.2016.529 -
Journal of Crohn's & Colitis Feb 2020Based on genetics and natural history, Crohn's disease can be separated into two entities, an ileal and a colonic disease. Protein-based approaches are needed to...
BACKGROUND AND AIMS
Based on genetics and natural history, Crohn's disease can be separated into two entities, an ileal and a colonic disease. Protein-based approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes.
METHODS
The proteome of ulcer edges was compared with that of paired control tissue samples [n = 32 biopsies] by differential proteomics in the ileum and the colon of Crohn's disease patients [n = 16]. The results were analysed using a hypothesis-driven approach [based on the literature] and a hypothesis-free approach [pathway enrichment analyses] to determine common and segment-specific pathophysiological processes associated with ileal and colonic CD ulcer edges. To confirm the involvement of a key pathway highlighted by proteomics, two proteins were also studied by immunochemistry.
RESULTS
In the ileum and the colon, 4428 and 5204 proteins, respectively, were identified and quantified. Ileal and colonic ulcer edges differed in having a distinct distribution of proteins associated with epithelial-mesenchymal transition, neutrophil degranulation, and ribosomes. Ileal and colonic ulcer edges were similarly characterized by an increase in the proteins implicated in the endoplasmic reticulum protein-processing pathway and a decrease in mitochondrial proteins. Immunochemistry confirmed the presence of endoplasmic reticulum stress in the mucosa of ileal and colonic ulcer edges.
CONCLUSION
This study provides protein-based evidence for partially distinct pathophysiological processes being associated with ileal and colonic ulcer edges in Crohn's disease patients. This could constitute a first step toward the development of gut segment-specific diagnostic markers and therapeutics.
Topics: Adult; Aged; Colon; Colonic Diseases; Crohn Disease; Female; Humans; Ileal Diseases; Ileum; Male; Middle Aged; Proteomics; Ulcer
PubMed: 31282946
DOI: 10.1093/ecco-jcc/jjz130 -
BMJ Open Gastroenterology Feb 2023To infer potential mechanisms driving disease subtypes among patients with inflammatory bowel disease (IBD), we profiled the transcriptome of purified circulating...
OBJECTIVE
To infer potential mechanisms driving disease subtypes among patients with inflammatory bowel disease (IBD), we profiled the transcriptome of purified circulating monocytes and CD4 T-cells.
DESIGN
RNA extracted from purified monocytes and CD4 T-cells derived from the peripheral blood of 125 endoscopically active patients with IBD was sequenced using Illumina HiSeq 4000NGS. We used complementary supervised and unsupervised analytical methods to infer gene expression signatures associated with demographic/clinical features. Expression differences and specificity were validated by comparison with publicly available single cell datasets, tissue-specific expression and meta-analyses. Drug target information, druggability and adverse reaction records were used to prioritise disease subtype-specific therapeutic targets.
RESULTS
Unsupervised/supervised methods identified significant differences in the expression profiles of CD4 T-cells between patients with ileal Crohn's disease (CD) and ulcerative colitis (UC). Following a pathway-based classification (Area Under Receiver Operating Characteristic - AUROC=86%) between ileal-CD and UC patients, we identified MAPK and FOXO pathways to be downregulated in UC. Coexpression module/regulatory network analysis using systems-biology approaches revealed mediatory core transcription factors. We independently confirmed that a subset of the disease location-associated signature is characterised by T-cell-specific and location-specific expression. Integration of drug-target information resulted in the discovery of several new (, , ) and repurposable drug targets (, ) for ileal CD as well as novel targets (, ) for UC.
CONCLUSIONS
Transcriptomic profiling of circulating CD4 T-cells in patients with IBD demonstrated marked molecular differences between the IBD-spectrum extremities (UC and predominantly ileal CD, sandwiching colonic CD), which could help in prioritising particular drug targets for IBD subtypes.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Gene Expression Profiling; Ileum; Nucleotide Transport Proteins
PubMed: 36746519
DOI: 10.1136/bmjgast-2022-001003 -
Ostomy/wound Management Jan 2010An ileal conduit is the most common urinary diversion following radical cystectomy for invasive bladder cancer. Unlike internal complications commonly described in... (Review)
Review
An ileal conduit is the most common urinary diversion following radical cystectomy for invasive bladder cancer. Unlike internal complications commonly described in urological literature, reports about the incidence of external complications are sparse. A Medline database review (1996-2008) of English-language literature was conducted to: 1) describe and compare external stoma and peristomal complications and complication rates among outpatients with ileal conduit diversion following radical cystectomy, and 2) summarize commonly used prevention and management strategies. Fourteen publications (mostly retrospective, single-center studies) met inclusion criteria. The reported incidence of complications ranged from 15% to 65%. Divided according to pathogenesis, the most commonly reported complications are 1) stoma or abdominal wall-related changes--parastomal hernia, stoma prolapse, stenosis, and retraction; and 2) peristomal skin changes--chemical injury: irritant contact dermatitis, pseudoverrucous lesions, and alkaline crustations; mechanical injury: pressure ulcers, skin stripping injuries, mucocutaneous separation; infection: candidiasis, folliculitis; immunologic disorders: allergic contact dermatitis; and disease-related lesions: varices, pyoderma gangrenosum, malignancy. Peristomal complications also appear to be under-recognized and under-reported. Research to establish the validity and reliability of assessment tools and long-term follow-up studies are needed to improve the evidence-base of prevention and care.
Topics: Cystectomy; Humans; Ileum; Surgical Stomas
PubMed: 20093715
DOI: No ID Found