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Objective Perfusion Rate Assessment by Near-infrared Fluorescence in Ileal Pouch Formation and Ileal-pouch-anal Anastomosis

ABSTRACT: In this prospective, non-randomized cohort study, real-time intraoperative visualization using near-infrared-fluorescence by indocyanine green injection (ICG-NIRF) is performed at three time points during ileal pouch reconstruction. Postoperatively, a detailed software-based assessment of each pouch recording is performed to determine the objective ICG-NIRF perfusion rate, which is then correlated with the 30 day postoperative clinical outcome including occurrence of anastomotic leak of the pouch.

DISEASE(S): Colitis, Ulcerative,Ulcerative Colitis In Remission,Ileal Pouch,Ulcerative Colitis,Adenomatous Polyposis Coli,Colorectal Cancer,Ulcerative Colitis Chronic,Crohn Disease,Familial Adenomatous Polyposis,Crohn Colitis,Colitis

PROVIDER: 2362864 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Subjective Near-infrared Fluorescence Guidance in Perfusion Assessment of Ileal Pouch Formation and Ileal-pouch-anal Anastomosis

Project description:In this prospective, non-randomized cohort study, real-time intraoperative visualization using near-infrared-fluorescence by indocyanine green injection (ICG-NIRF) is performed at three time points during ileal pouch reconstruction. The intraoperative imaging findings are then analysed and correlated with the 30 day postoperative clinical outcome including occurrence of anastomotic leak of the pouch.

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Transcriptional Survey of Ileal-Anal Pouch Immune Cells from Ulcerative Colitis

Project description:Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the most common complication, is inflammation of the pouch of unknown etiology. To define how the intestinal immune system is distinctly organized in response to inflammation and to develop mechanistic hypotheses of pouchitis, we analyzed tissues from patients with and without pouchitis and from patients with ulcerative colitis using single-cell RNA sequencing. We examined pouch lamina propria CD45+ hematopoietic cells from intestinal tissues of ulcerative colitis patients with (n=15) and without an ileal pouch-anal anastomosis (n=11). Further in silico meta-analysis was performed to generate transcriptional interaction networks and identify drug targets for patients with inflamed pouches. We identified a population of IL1B+ antimicrobial macrophages and FOXP3+/BATF+ T cells that are expanded in inflamed tissues, which we further validated in other single cell RNA-seq datasets from IBD patients. Cell type specific markers obtained from single-cell RNA-sequencing was used to infer representation from bulk RNA sequencing datasets, which further implicated antimicrobial macrophages expressing IL1B with S100A8/A9 calprotectin as being associated with inflammation, and Bacteroidiales and Clostridiales bacterial taxa. We found that non-responsiveness to anti-integrin biologic therapies in ulcerative colitis patients was associated with the signature of this antimicrobial macrophage population in a subset of patients. This study identified conserved and distinct features of intestinal inflammation between parts of the small and large intestine undergoing similar inflammation conditions. Specifically, we relate inflammation of the pouch, a surgically constructed organ, to other inflammatory contexts throughout the gastrointestinal tract.

2020-12-01 | GSE162335 | GEO

Ileal pouch transcriptomics reveal shared pathogenesis between pouchitis and ulcerative colitis

Project description:UC pouchitis is a potential model of UC. We prospectively examined the pouch transcriptomes of UC and familial adenomatous polyposis (FAP) IPAA patients to unveil molecular mechanisms of UC pouchitis susceptibility. Methods: Total RNA was isolated using the AllPrep DNA/RNA Mini Kit (QIAGEN, Cat No. 8020). RNA quality was evaluated using Bioanalyzer (Agilent, Santa Clara, CA). All RNA samples displayed RNA Integrity Number (RIN) >7. RNAseq including cDNA library preparation was processed at the Genomics Core Facility of University of Chicago (https://fgf.uchicago.edu/). Total RNA in the amount of 100-500μg per sample was depleted of ribosomal RNA using the Ribo-Zero kit (Epicentre, Madison, WI). The directional (first strand) cDNA libraries were prepared following the guide of TruSeq Stranded Total RNA Sample Preparation kit. Results: Unlike FAP patients, UC subjects exhibited a large set of differentially expressed genes (DEGs) between pouch and pre-pouch mucosa as early as 4 months after pouch functionalization. Functional pathway analysis of DEGs in UC pouch revealed: (1) Gain of colon-associated gene expressions and loss of ileum associated gene expressions, (2) enhanced state of immune/inflammatory response, and (3) suppressed xenobiotic, lipid, and bile acid metabolic pathways. These changes were corroborated upon reanalysis of a published larger cross-sectional study of UC and FAP patients. Moreover, >70% of DEGs mapped to published IBD and normal colonic microarray datasets displayed directional changes consistent with active UC, but not Crohn's disease. Conclusions: UC patients exhibit a unique transcriptomic response to ileal pouch creation that can be observed well before disease. The transcriptome alterations provide insights into pouchitis

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Characterization of the Gut-Associated Microbiome in Inflammatory Pouch Complications Following Ileal Pouch-Anal Anastomosis

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Project description:In this prospective, non-randomized cohort study, real-time intraoperative visualization using near-infrared-fluorescence by indocyanine green injection (ICG-NIRF) is performed at two to three time points during procedures of upper GI, lower GI and hepatobiliary surgery with anastomosis formation in open or laparoscopic surgery. Postoperatively, a detailed software-based assessment of each recording is performed to determine the objective ICG-NIRF perfusion rate before and after anastomosis formation, which is then correlated with the 30 day postoperative clinical outcome including occurrence of anastomotic leak.

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Transcriptional Survey of Ileal-Anal Pouch Immune Cells from Ulcerative Colitis

Project description:Transcriptional Survey of Ileal-Anal Pouch Immune Cells from Ulcerative Colitis

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Microarray analysis from paired biopsies from ileal pouch-anal anastomosis surgery patients with ulcerative colitis and familial adenomatous polyposis

Project description:Pouchitis is a common complication for ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA) surgery. Similarly to IBD, both innate host factors such as genetics, and environmental stimuli including the tissue-associated microbiome have been implicated in the pathogenesis. In this study, we make use of the IPAA model of inflammatory bowel disease (IBD) to carry out a study associating mucosal host gene expression with the microbiome and corresponding clinical outcomes. In order to determine how host gene expression might influence, or be influenced by the tissue associated microbiome, we analyzed 205 IPAA patients with biopsies collected from the pouch and afferent limb for host transcriptomics and 16S rDNA gene sequencing. Metadata included antibiotic use, inflammation score, and clinical classification. To achieve power for a genome-wide microbiome-transcriptome association study, we used principal component analysis to reduce OTUs and host transcripts to eigengenes and eigenclades explaining 50% of observed variance. These were subsequently tested for significant covariation with one another and/or outcome using multivariate linear modeling.

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