Technical aspects of ileoanal pouch surgery in patients with ulcerative colitis.
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ABSTRACT:
SUBMITTER: Kirat HT
PROVIDER: S-EPMC3134803 | biostudies-other | 2010 Dec
REPOSITORIES: biostudies-other
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Project description:BackgroundTotal proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is the gold standard surgery for ulcerative colitis (UC) patients with medically refractory disease. The aim of this study was to report the rates and risk factors of inflammatory pouch conditions.MethodsThis was a retrospective review of UC or IBD unspecified (IBDU) patients who underwent TPC with IPAA for refractory disease or dysplasia between 2008 and 2017. Pouchoscopy data were used to calculate rates of inflammatory pouch conditions. Factors associated with outcomes in univariable analysis were investigated in multivariable analysis.ResultsOf the 621 patients more than 18 years of age who underwent TPC with IPAA between January 2008 and December 2017, pouchoscopy data were available for 386 patients during a median follow-up period of 4 years. Acute pouchitis occurred in 205 patients (53%), 60 of whom (30%) progressed to chronic pouchitis. Cuffitis and Crohn's disease-like condition (CDLC) of the pouch occurred in 119 (30%) patients and 46 (12%) patients, respectively. In multivariable analysis, female sex was associated with a decreased risk of acute pouchitis, and pre-operative steroid use and medically refractory disease were associated with an increased risk; IBDU was associated with chronic pouchitis; rectal cuff length ≥2 cm and medically refractory disease were associated with cuffitis; age 45-54 at colectomy was associated with CDLC. Rates of pouch failure were similar in chronic pouchitis and CDLC patients treated with biologics and those who were not.ConclusionsInflammatory pouch conditions are common. Biologic use for chronic pouchitis and CDLC does not impact the rate of pouch failure.
| S-EPMC7456971 | biostudies-literature
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.
2015-01-27 | E-GEOD-65270 | biostudies-arrayexpress
Project description:Total retocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice for patients with ulcerative colitis (UC) that are refractory to clinical treatment. Pouchitis is one of the most common complications after this procedure. Defects in autophagy have been reported in inflammatory bowel diseases. However, there are no studies on the IP. Therefore, we studied markers for autophagy in the IP mucosa of UC and FAP patients comparing them to controls with a normal distal ileum. Sixteen patients with IP in "J" shape, asymptomatic and with endoscopically normal IP were evaluated. The control group consisted of eight patients with normal colonoscopy. There was a significant decrease in the transcriptional levels of ATG5, MAP1LC3A and BAX in the FAP group. There was also a decrease in the protein level of Beclin-1 in the UC and FAP compared to the control group. Although the LC3II levels by immunoblot were higher in the UC group, LC3/p62 co-localization were lower in the immunofluorescence analysis in the UC and FAP compared to the control group. Corroborating these results, there was an increase of p62 by immunoblot in the UC group. These findings indicated a modulation of macroautophagy markers in the IP, which may explain the mucosa inflammation predisposition.
| S-EPMC5805688 | biostudies-other
Project description:Background and aimsThe ileoanal pouch (IPAA) provides patients with ulcerative colitis (UC) that have not responded to medical therapy an option to retain bowel continuity and defecate without the need for a long-term stoma. Despite good functional outcomes, some pouches fail, requiring permanent diversion, pouchectomy, or a redo pouch. The incidence of pouch failure ranges between 2 and 15% in the literature. We conducted a systematic review and meta-analysis aiming to define the prevalence of pouch failure in patients with UC who have undergone IPAA using population-based studies.MethodsWe searched Embase, Embase classic and PubMed from 1978 to 31st of May 2021 to identify cross-sectional studies that reported the prevalence of pouch failure in adults (≥ 18 years of age) who underwent IPAA for UC.ResultsTwenty-six studies comprising 23,389 patients were analysed. With < 5 years of follow-up, the prevalence of pouch failure was 5% (95%CI 3-10%). With ≥ 5 but < 10 years of follow-up, the prevalence was 5% (95%CI 4-7%). This increased to 9% (95%CI 7-16%) with ≥ 10 years of follow-up. The overall prevalence of pouch failure was 6% (95%CI 5-8%).ConclusionsThe overall prevalence of pouch failure in patients over the age of 18 who have undergone restorative proctocolectomy in UC is 6%. These data are important for counselling patients considering this operation. Importantly, for those patients with UC being considered for a pouch, their disease course has often resulted in both physical and psychological morbidity and hence providing accurate expectations for these patients is vital.
| S-EPMC8803821 | biostudies-literature
Project description:Proctitis after subtotal colectomy with ileostomy for ulcerative colitis [UC] is common, but its impact on short- and long-term outcome after pouch surgery is unknown. The aim of this study was to determine the incidence of proctitis after subtotal colectomy and its impact on postoperative morbidity and pouchitis. The distal margin of the rectal stump of all consecutive patients undergoing completion proctectomy and pouch procedure for UC, between 1999 and 2017, was revised and scored for active inflammation according to the validated Geboes score, and for diversion proctitis. Pathological findings were correlated to complications after pouch surgery and pouchitis [including therapy-refractory] using multivariate analyses. Out of 204 included patients, 167 [82%] had active inflammation in the rectal stump and diversion colitis was found in 170 specimens [83%]. Overall postoperative complications and anastomotic leakage rates were not significantly different between patients with and without active inflammation in the rectal stump [34.7% vs 32.4%, p = 0.79, and 10.2% vs 5.4%, p = 0.54, respectively]. Active inflammation of the rectal stump was significantly associated with the development of pouchitis [54.3% vs 25.5%, plog = 0.02], as well as with therapy refractory pouchitis [14% vs 0%, plog = 0.05]. Following multivariate analysis, active inflammation was an independent predictor for the development of pouchitis. Diversion proctitis showed no association with these outcome parameters. Active inflammation in the rectal stump after subtotal colectomy occurs in 80% of UC patients and is a predictor for the development of pouchitis and therapy-refractory pouchitis.
| S-EPMC7904055 | biostudies-literature
Project description:The pathogenesis of ulcerative colitis (UC) is unknown, although genetic loci and altered gut microbiota have been implicated. Up to a third of patients with moderate to severe UC require proctocolectomy with ileal pouch ano-anastomosis (IPAA). We aimed to explore the mucosal microbiota of UC patients who underwent IPAA. For microbiome analysis, mucosal specimens were collected from 34 IPAA individuals. Endoscopic and histological examinations of IPAA were normal in 21 cases, while pouchitis was in 13 patients. 19 specimens from the healthy control (10 from colonic and 9 from ileum) were also analyzed. Data were analyzed using an ensemble of software packages: QIIME2, coda-lasso, clr-lasso, PICRUSt2, and ALDEx2. IPAA specimens had significantly lower bacterial diversity as compared to normal. The microbial composition of the normal pouch was also decreased also when compared to pouchitis. Faecalibacterium prausnitzii, Gemmiger formicilis, Blautia obeum, Ruminococcus torques, Dorea formicigenerans, and an unknown species from Roseburia were the most uncommon in pouch/pouchitis, while an unknown species from Enterobacteriaceae was over-represented. Propionibacterium acnes and Enterobacteriaceae were the species most abundant in the pouchitis and in the normal pouch, respectively. Predicted metabolic pathways among the IPAA bacterial communities revealed an important role of immunometabolites such as SCFA, butyrate, and amino acids. Our findings showed specific bacterial signature hallmarks of dysbiosis and could represent bacterial biomarkers in IPAA patients useful to develop novel treatments in the future by modulating the gut microbiota through the administration of probiotic immunometabolites-producing bacterial strains and the addition of specific prebiotics and the faecal microbiota transplantation.
| S-EPMC8624401 | biostudies-literature
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
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
2016-05-11 | GSE81266 | GEO
Project description:BackgroundUp to 30% of patients with ulcerative colitis will undergo surgery resulting in an ileal pouch-anal anastomosis (IPAA) or permanent end ileostomy (EI). We aimed to understand how patients decide between these two options.MethodsWe performed semi-structured interviews with ulcerative colitis patients who underwent surgery. Areas of questioning included the degree to which patients participated in decision-making, challenges experienced, and suggestions for improving the decision-making process. We analyzed the data using a directed content and thematic approach.ResultsWe interviewed 16 patients ranging in age from 28 to 68 years. Nine were male, 10 underwent IPAA, and 6 underwent EI. When it came to participation in decision-making, 11 patients felt independently responsible for decision-making, 3 shared decision-making with the surgeon, and 2 experienced surgeon-led decision-making. Themes regarding challenges during decision-making included lack of support from family, lack of time to discuss options with the surgeon, and the overwhelming complexity of the decision. Themes for ways to improve decision-making included the need for additional information, the desire for peer education, and earlier consultation with a surgeon. Only 3 patients were content with the information used to decide about surgery.ConclusionsPatients with ulcerative colitis who need surgery largely experience independence when deciding between IPAA and EI, but struggle with inadequate educational information and social support. Patients may benefit from early access to surgeons and peer guidance to enhance independence in decision-making. Preoperative educational materials describing surgical complications and postoperative lifestyle could improve decision-making and facilitate discussions with loved ones.
| S-EPMC8451075 | biostudies-literature
Project description:Background: Ulcerative colitis (UC) develops from chronic inflammation of the colon. Most patients respond favorably to medical management, however around 25% of UC patients will require surgery to treat their disease. While surgery is the only curative treatment for UC, it can carry its own risks, particularly when the surgery is emergent. Time from diagnosis to surgery varies dramatically amongst UC patients, thus a better understanding of how the colonic microenvironment relates to disease severity is needed to improve patient outcomes. Methods: We conducted RNA-seq on full-thickness sigmoid colonic tissues from 26 UC patients undergoing colectomy for their disease. Hierarchical clustering of the transcriptomes identified disease subsets. Subsets were characterized using differential gene expression analysis, cell type deconvolution, and network analysis. Results: We identified two distinct UC subsets in our cohort that were distinguished by 957 differentially expressed genes. Cluster 1 was enriched in genes associated with intestinal epithelial cell differentiation, while cluster 2 was enriched in genes associated with epithelial-to-mesenchymal transition and inflammatory responses. Cluster 1 was associated with an extended time from UC diagnosis to colectomy. Of cluster 1 genes, elevated MUC5B, MUC4, and MUC2 expression displayed the strongest correlation with increased time to surgery. Conclusion: Our transcriptome analysis indicates that UC can be subclassified into at least two distinct molecular signatures. We find that elevated mucin gene expression correlates with prolonged time to colectomy after diagnosis. These results identified MUC5B, MUC4, and MUC2 as potential prognostic indicators of disease severity, as reflected in time to surgery.
2020-04-18 | GSE130038 | GEO