Chronic nonspecific inflammatory bowel disease of the cecum and proximal colon in children with grossly normal-appearing colonic mucosa: Diagnosis by colonoscopic biopsies

The diagnosis of inflammatory bowel disease rests on radiologic, endoscopic, and histologic creteria. Five patients, 2 to 17 years of age, sought medical attention because of chronic abdominal pain, diarrhea, and heme-positive stools. Rectal biopsies, visual inspection of colonic mucosa through the colonoscope, and contrast radiographs of the large and small intestine yielded nonspecific results. Serial endoscopic biopsies demonstrated a gradient of inflammatory changes diminishing in severity distally from the ileocecal valve and cecum. The disease process was most evident in specimens from the cecum, whereas biopsies distal to the transverse colon had a normal histologic appearance in all five patients. Biopsies from the proximal colon may provide evidence of inflammatory bowel disease not detectable using standard techniques. The combination of chronic abdominal pain, diarrhea, and heme-positive stools associated with inflammatory changes in biopsy specimens obtained from the proximal colon, but normal findings on radiologic, colonoscopic, and rectal biopsy examinations, may represent an early stage in the evolution of chronic nonspecific inflammatory bowel disease, including ulcerative colitis or regional enteritis (Crohn disease).

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Multi-Omics Characterization of Inflammatory Bowel Disease-Induced Hyperplasia/Dysplasia in the Rag2−/−/Il10−/− Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms22010364 ◽

2020 ◽

Vol 22 (1) ◽

pp. 364

Author(s):

Qiyuan Han ◽

Thomas J. Y. Kono ◽

Charles G. Knutson ◽

Nicola M. Parry ◽

Christopher L. Seiler ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Gastrointestinal Disease ◽

Tumor Development ◽

Proximal Colon ◽

Helicobacter Hepaticus ◽

Reduced Representation ◽

Reduced Representation Bisulfite Sequencing ◽

Inflammatory Bowel

Epigenetic dysregulation is hypothesized to play a role in the observed association between inflammatory bowel disease (IBD) and colon tumor development. In the present work, DNA methylome, hydroxymethylome, and transcriptome analyses were conducted in proximal colon tissues harvested from the Helicobacter hepaticus (H. hepaticus)-infected murine model of IBD. Reduced representation bisulfite sequencing (RRBS) and oxidative RRBS (oxRRBS) analyses identified 1606 differentially methylated regions (DMR) and 3011 differentially hydroxymethylated regions (DhMR). These DMR/DhMR overlapped with genes that are associated with gastrointestinal disease, inflammatory disease, and cancer. RNA-seq revealed pronounced expression changes of a number of genes associated with inflammation and cancer. Several genes including Duox2, Tgm2, Cdhr5, and Hk2 exhibited changes in both DNA methylation/hydroxymethylation and gene expression levels. Overall, our results suggest that chronic inflammation triggers changes in methylation and hydroxymethylation patterns in the genome, altering the expression of key tumorigenesis genes and potentially contributing to the initiation of colorectal cancer.

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