Raffals, Laura E.

Abstract Background and study aims Chronically inflamed colonic mucosa is primed to develop dysplasia identified at surveillance colonoscopy by targeted or random biopsies. We aimed to explore the effect of mucosal inflammation on detection of visible and “invisible” dysplasia and the concordance between the degree of endoscopic and histologic inflammation. Patients and methods This was a 6-year cross-sectional analysis of endoscopic and histologic data from IBD. A multinomial model was created to estimate the odds for a specific lesion type as well as the odds of random dysplasia relative to the degree of inflammation. Kappa statistics were used to measure concordance between endoscopic and histologic inflammation. Results A total of 3437 IBD surveillance colonoscopies between 2016–2021 were reviewed with 970 procedures from 721 patients containing 1603 visible lesions. Kappa agreement between histologic and endoscopic degree of inflammation was low at 0.4. There was a positive association between increased endoscopic inflammation and presence of tubulovillous adenomas (TVAs) (odds ratio [OR] 2.18; 95% confidence interval [CI] 1.03–4.62; P=0.04). Among cases with visible lesions, the yield of concomitant random dysplasia was 2.7% and 1.9% for random indefinite dysplasia. The odds of random dysplasia significantly increased as the degree of endoscopic and histologic inflammation increased (OR 2.18, 95%CI 1.46–3.26; P<0.001 and OR 2.75; 95%CI 1.65–4.57, P<0.001, respectively. The odds of indefinite random dysplasia also significantly increased as endoscopic and histologic inflammation increased (OR 2.90; 95%CI 1.85, 4.55, P<0.001 and OR 1.98; 95%CI 1.08, 3.62, P<0.035, respectively. Conclusions Endoscopic and histologic inflammation are associated with higher odds of finding TVAs and random low-grade, high-grade, and indefinite dysplasia. Concordance between histologic and endoscopic inflammation severity is low.

Background Forty distinct primary sclerosing cholangitis (PSC) genomic loci have been identified through multiancestry meta-analyses. The polygenic risk score (PRS) could serve as a promising tool to discover unique disease behaviour, like PSC, underlying inflammatory bowel disease (IBD). Aim To test whether PRS indicates PSC risk in patients with IBD. Materials and methods Mayo Clinic and Washington University at St Louis IBD cohorts were used to test our hypothesis. PRS was modelled through the published PSC loci and weighted with their corresponding effect size. Logistic regression was applied to predict the PSC risk. Results In total, 63 (5.6%) among 1130 patients with IBD of European ancestry had PSC. Among 381 ulcerative colitis (UC), 12% had PSC; in contrast to 1.4% in 761 Crohn disease (CD). Compared with IBD alone, IBD-PSC had significantly higher PRS (PSC risk: 3.0% at the lowest PRS quartile vs 7.2% at the highest PRS quartile, Ptrend =.03). In IBD subphenotypes subgroup analysis, multivariate analysis shows that UC-PSC is associated with more extensive UC disease (OR, 5.60; p=0.002) and younger age at diagnosis (p=0.02). In CD, multivariate analysis suggests that CD-PSC is associated with colorectal cancer (OR, 50; p=0.005). Conclusions We found evidence that patients with IBD with PSC presented with a clinical course difference from that of patients with IBD alone. PRS can influence PSC risk in patients with IBD. Once validated in an independent cohort, this may help identify patients with the highest likelihood of developing PSC.

INTRODUCTION: The American Gastroenterological Association (AGA) has compiled risk factors that may be predictive of disease complications in Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate the performance of the AGA risk factors for risk stratification in UC and CD. METHODS: We included participants of 2 cohorts: the Ocean State Crohn's and Colitis Area Registry cohort and the Mayo Clinic cohort. Baseline clinical risk factors were extracted according to the AGA pathway. Our primary end point was defined as follows: (i) any inflammatory bowel disease related–hospitalization, (ii) any inflammatory bowel disease–related bowel surgery, or (iii) any progression of disease. We analyzed the association of the number of AGA risk factors with our end point. Statistical multivariable modeling was performed with Cox proportional hazards model. RESULTS: A total of 412 patients with CD were included. Comparing ≥3 risk factors with 0–1 risk factor, we found a significantly increased risk of complications in both the Ocean State Crohn's and Colitis Area Registry cohort (hazard ratio [HR] 2.75, 95% confidence interval 1.71–4.41) and Mayo Clinic cohort (HR 2.07, 95% confidence interval 1.11–3.84). Diagnosis at younger age (HR 2.07), perianal disease (HR 1.99), and B2/B3 behavior (HR 1.92) were significantly associated with disease complications. We did not observe a consistent association between number of risk factors nor any specific individual risk factors and risk of disease complications in the 265 patients with UC included. DISCUSSION: We found a significant association between the number of AGA risk factors and the risk of disease complication in CD; this association was not significant in UC. The presence of ≥ 3 risk factors in CD leads to the highest risk of complications. The AGA care pathway is a useful tool to stratify patients who are at higher risk of disease complications in patients with CD.

INTRODUCTION: Patients with ulcerative colitis (UC) who are likely to have primary sclerosing cholangitis (PSC) should be identified because PSC can influence UC clinical behavior and outcomes.The aim of this study was to establish a model incorporating clinical and genetic risk predictors that identifies patients with UC at risk of developing PSC. METHODS: We conducted a retrospective case-control study. Inflammatory bowel disease cohorts from multiple institutions were used as discovery and replicate datasets. Quality control criteria, including minor allele frequency, call rates, Hardy-Weinberg equilibrium, cryptic relatedness, and population stratification (through principal components), were used. Discriminative accuracy was evaluated with area under the receiver operating characteristic curve. RESULTS: Fifty-seven of 581 patients (9.8%) with UC had PSC. Multivariate analysis showed that patients with UC-PSC had more extensive disease (odds ratio [OR], 5.42; P = 1.57E-04), younger diagnosis age (younger than 20 years; OR, 2.22; P = 0.02), and less smoking (OR, 0.42; P = 0.02) than those with UC. After linkage disequilibrium pruning and multivariate analyses, 3 SNPs (rs3131621 at 6p21.33; rs9275596 and rs11244 at 6p21.32) at the HLA region were found associated with a 2- to 3-fold increased risk of PSC. Our model demonstrated good discriminatory power (area under the receiver operating characteristic curve, 88%). DISCUSSION: Three variants in HLA (6p21.3) region significantly distinguished patients with UC-PSC from patients with UC alone. Once further validated in an independent large cohort, our model could be used to identify patients with UC at risk of PSC, and it could also help guide disease management.

Total abdominal proctocolectomy with ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC) is associated with substantial complications despite the benefits of managing refractory and/or neoplasia-associated disease. For the purpose of this review, we focused on the diagnosis of some of the most common inflammatory and structural pouch disorders and their respective management. Pouchitis is the most common complication, and it is typically responsive to antibiotics. However, chronic antibiotic refractory pouchitis (CARP) has been increasingly recognized, and biologic therapies have emerged as the mainstay of therapy. Crohn's-like disease of the pouch (CLDP) can affect up to 10% of patients with UC after IPAA. Medical options are similar to CARP therapies, including biologics with immunomodulators. Studies have shown higher efficacy rates of biologics for CLDP when compared with those for CARP. In addition, managing stricturing and fistulizing CLDP is challenging and often requires interventional endoscopy (balloon dilation and/or stricturotomy) and/or surgery. The implementation of standardized diagnostic criteria for inflammatory pouch disorders will help in advancing future therapeutic options. Structural pouch disorders are commonly related to surgical complications after IPAA. We focused on the diagnosis and management of anastomotic leaks, strictures, and floppy pouch complex. Anastomotic leaks and anastomotic strictures occur in approximately 15% and 11% of patients with UC after IPAA, respectively. Further complications from pouch leaks include the development of sinuses, fistulas, and pouch sepsis requiring excision. Novel endoscopic interventions and less invasive surgical procedures have emerged as options for the management of these disorders.

Abstract Background Ileal pouch–anal anastomosis (IPAA) is the standard restorative procedure following proctocolectomy in patients with inflammatory bowel disease (IBD) who require colectomy. However, removal of the diseased colon does not eliminate the risk of pouch neoplasia. We aimed to assess the incidence of pouch neoplasia in IBD patients following IPAA. Methods All patients at a large tertiary center with International Classification of Diseases–Ninth Revision/International Classification of Diseases–Tenth Revision codes for IBD who underwent IPAA and had subsequent pouchoscopy were identified using a clinical notes search from January 1981 to February 2020. Relevant demographic, clinical, endoscopic, and histologic data were abstracted. Results In total, 1319 patients were included (43.9% women). Most had ulcerative colitis (95.2%). Out of 1319 patients, 10 (0.8%) developed neoplasia following IPAA. Neoplasia of the pouch was seen in 4 cases with neoplasia of the cuff or rectum seen in 5 cases. One patient had neoplasia of the prepouch, pouch, and cuff. Types of neoplasia included low-grade dysplasia (n = 7), high-grade dysplasia (n = 1), colorectal cancer (n = 1), and mucosa-associated lymphoid tissue lymphoma (n = 1). Presence of extensive colitis, primary sclerosing cholangitis, backwash ileitis, and rectal dysplasia at the time of IPAA were significantly associated with increased risk of pouch neoplasia. Conclusions The incidence of pouch neoplasia in IBD patients who have undergone IPAA is relatively low. Extensive colitis, primary sclerosing cholangitis, and backwash ileitis prior to IPAA and rectal dysplasia at the time of IPAA raise the risk of pouch neoplasia significantly. A limited surveillance program might be appropriate for patients with IPAA even with a history of colorectal neoplasia.

Background: Obesity is on the rise within the inflammatory bowel disease population. The impact obesity has on the natural history of Crohn’s disease (CD) is not well-understood. We aimed to describe the prevalence of obesity in a population-based cohort of newly diagnosed patients with CD, and the impact obesity had on disease phenotype and outcomes of corticosteroid use, hospitalization, intestinal resection, and development of fistulizing or penetrating disease. Materials and Methods: A chart review was performed on Olmsted County, Minnesota residents diagnosed with CD between 1970 and 2010. Data were collected on demographics, body mass index, CD location and behavior, CD-related hospitalizations, corticosteroid use, and intestinal resection. The proportion of individuals considered obese at the time of CD diagnosis was evaluated over time, and CD-associated complications were assessed with Kaplan-Meier survival analysis. Results: We identified 334 individuals diagnosed with CD between 1970 and 2010, of whom 156 (46.7%) were either overweight (27.8%) or obese (18.9%) at the time of diagnosis. The proportion of patients considered obese at the time of their diagnosis of CD increased 2-3 fold over the course of the study period. However, obesity did not have a significant impact on the future risk of corticosteroid use, hospitalization, intestinal resection, or development of penetrating and stricturing complications. Conclusions: Obesity is on the rise in patients with CD, although in this cohort, there did not appear to be any negative association with future CD-related outcomes. Further prospective studies, ideally including obesity measures such as visceral adipose tissue assessment, are warranted to understand the implications of the rising prevalence of obesity on CD outcomes.