Inflammatory Bowel Disease and Small Bowel Cancer Risk, Clinical Characteristics, and Histopathology: A Population-Based Study

Bojesen, Rasmus Dahlin; Riis, Lene; Høgdall, Estrid; Nielsen, Ole Haagen; Jess, Tine

doi:10.1016/j.cgh.2017.06.051

Cited by 62 publications

(70 citation statements)

References 48 publications

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“…Although incompletely understood, GI inflammation‐mediated progression to cancer development might involve bacterial toxin production, release of alarmins, gut biofilm modification, dysregulation of gut barrier function, suppression of anti‐inflammatory mediators and transition through an element of high grade dysplasia to cell damage and aneuploidy 13, 19, 35, 40, 60, 61, 62…”

Section: Discussionmentioning

confidence: 99%

“…; Fuso0664, Fusobacterium spp.. transition through an element of high grade dysplasia to cell damage and aneuploidy. 13,19,35,40,[60][61][62] Fusobacterium spp. is pro-inflammatory, exhibits adhesive and invasive properties via virulence factors (i.e., FadA, fusobacterium autotransporter protein 2 and fusobacterial outer membrane protein A), and promotes pro-oncogenic features which might contribute to accelerated tumor growth and tumor burden.…”

Section: Discussionmentioning

confidence: 99%

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Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Garraway

Johannes

Bryan

et al. 2018

Veterinary Internal Medicne

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BackgroundThe gastrointestinal (GI) microbiota in healthy cats is altered in IBD. Little research has been performed to identify whether specific bacterial groups are associated with small cell GI lymphoma (LSA).HypothesisMucosal bacteria, including Enterobacteriaceae and Fusobacterium spp., are abundant in intestinal biopsies of cats with small cell GI LSA compared to cats with IBD.AnimalsFourteen cats with IBD and 14 cats with small cell GI LSA.MethodsRetrospective case control study. A search of the medical records was performed to identify cats diagnosed with IBD and with GI LSA. Bacterial groups identified by FISH in GI biopsies were compared between cohorts and correlated to CD11b+ and NF‐κB expression.Results Fusobacterium spp. (median; IQR bacteria/region) were higher in cats with small cell GI LSA in ileal (527; 455.5 – 661.5; P = .046) and colonic (404.5; 328.8 – 455.5; P = .016) adherent mucus, and combined colonic compartments (free mucus, adherent mucus, attaching to epithelium) (8; 0 – 336; P = .017) compared to cats with IBD (ileum: 67; 31.5 – 259; colon: 142.5; 82.3 – 434.5; combined: 3; 0 – 34). Bacteroides spp. were higher in ileal adherent mucus (P = .036) and 3 combined ileal compartments (P = .034) of cats with small cell GI LSA. There were significant correlations between Fusobacterium spp. totals and CD11b+ cell (P = .009; rs .476) and NF‐κB expression (P = .004; rs .523).ConclusionsThe bacterial alterations appreciated might be influential in development of small cell GI LSA, and should drive further studies to elucidate the effects of microbial‐mediated inflammation on GI cancer progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Garraway

Johannes

Bryan

et al. 2018

Veterinary Internal Medicne

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“…In contrast to intestinal metaplasia in the esophagus and stomach, small intestinal UACL has not been related to an increased cancer risk. Recent reports have, however, pointed to an increased cancer risk also in small intestinal CD and one report suggested a connection between UACL and CD enteritis‐associated small bowel adenocarcinoma .…”

Section: Introductionmentioning

confidence: 99%

Ulcer‐associated cell lineage expresses genes involved in regeneration and is hallmarked by high neutrophil gelatinase‐associated lipocalin (NGAL) levels

Thorsvik

Granlund

Svendsen

et al. 2019

The Journal of Pathology

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Neutrophil gelatinase‐associated lipocalin (NGAL), also known as Lipocalin 2, is an antimicrobial protein, encoded by the gene LCN2 , strongly upregulated in inflammatory bowel disease (IBD) and a promising biomarker for IBD. Here we demonstrate that NGAL is highly expressed in all parts of pyloric metaplasia, also known as the ulcer‐associated cell lineage (UACL), a metaplastic cell lineage suggested to play a role in wound healing in Crohn's disease (CD). We further show NGAL expression in regenerative intestinal crypts and in undifferentiated patient‐derived colonoids. This indicates that NGAL is important in the tissue regeneration process. The remarkable overexpression of NGAL in UACL led us to explore the pathobiology of these cells by transcriptome‐wide RNA sequencing. This study is, to our knowledge, the first to characterize the UACL at this level. Biopsies with UACL and inflamed non‐UACL epithelium from the terminal ileum of CD patients and epithelium from healthy controls were laser capture microdissected for RNA sequencing. Among the 180 genes differentially expressed between UACL and control epithelium, the ten most‐upregulated genes specific for UACL were MUC5AC, PGC, MUC6, MUC5B, LCN2, POU2AF1, MUC1, SDC3, IGFBP5 , and SLC7A5 . PDX1 was among the most upregulated in both UACL and inflamed non‐UACL epithelium. Immunohistochemistry and iDisco 3D visualization was used to characterize UACL histo‐morphologically, and to validate protein expression of 11 selected differentially expressed genes. Among these genes, LCN2, NOTCH2, PHLDA1, IGFBP5, SDC3, BPIFB1 , and RCN1 have previously not been linked to UACL. Gene expression results were analyzed for functional implications using MetaCore, showing that differentially expressed genes are enriched for genes involved in cell migration and motility, and for biomarkers of gastrointestinal neoplasia. These results support a role for UACL as part of the reepithelialization process during and after destructive intestinal inflammation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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“…On the other hand, SBC often localise in the inflamed ileum in CrD [2,8], a form of relapsing transmural inflammatory bowel disease due to an abnormal immune response to commensal microbiota [9]. Most CrD-SBC are microsatellite stable, have low TILs and often show a non-glandular histotype coupled with a non-intestinal phenotype [2,7,8,[10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, small bowel resection and use of salicylates for more than two years protect against SBC in patients with CrD. 25 As regards gender, the rates of female prevalence are extremely heterogeneous in both CD-SBC (25-62%) [2,5,5,20,21] and CrD-SBC (29-60%) [2,8,[10][11][12][22][23][24][25][26][27][28][29] so that it is hard to assess a gender predominance in either conditions. However, considering the strong prevalence of CD in women [4], these data may suggest that male gender is at higher risk to develop CD-SBC.…”

Section: Introductionmentioning

confidence: 99%

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: the Current Knowledge

Giuffrida¹,

Vanoli²,

Arpa³

et al. 2018

Preprint

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Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders, including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumor-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC.

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Inflammatory Bowel Disease and Small Bowel Cancer Risk, Clinical Characteristics, and Histopathology: A Population-Based Study

Cited by 62 publications

References 48 publications

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Ulcer‐associated cell lineage expresses genes involved in regeneration and is hallmarked by high neutrophil gelatinase‐associated lipocalin (NGAL) levels

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: the Current Knowledge

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