Colorectal Dysplasia Research Articles

Preoperative Simulation of Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis Using a 3-Dimensional Printed Model.

During restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis-associated colorectal cancer or dysplasia, ileal pouch-anal handsewn anastomosis (IAA) is preferred to avoid the risk of cancer development in the remaining rectal mucosa. However, there is a risk of the ileal pouch not reaching the anus with this procedure. Here, we created deformable 3-dimensional (3D) models for simulation. Six patients who underwent IAA without vessel ligation and 5 patients who underwent ileal pouch-anal canal double-stapled anastomosis (IACA) because the ileal pouch did not reach the anus were studied. A 3D printer was used to create deformable 3D models from the data obtained from computed tomography scans. The positional relationship among the mesenteric arteries, pubis, and coccyx were evaluated. The distance between the superior mesenteric artery root and the tip of the ileal artery was longer in the IAA group than that in the IACA group (IAA vs IACA: 26.2 ± 2.1 cm vs 20.9 ± 1.6cm). The distance from the tip of the ileal artery to the coccyx (IAA vs IACA: 6.7 ± 1.7 cm vs 12.1 ± 2.1 cm) and the distance from the tip of the ileal artery to the lower edge of the pubis (IAA vs IACA; 8.1 ± 1.3 cm vs 12.7 ± 2.4 cm) were longer in the IACA group than those in the IAA group. We established a method for creating 3D deformable models of patients with ileal pouch-anal anastomosis. These 3D models may be useful for preoperative simulation.

Detection of Colorectal Adenocarcinoma and Grading Dysplasia on Histopathologic Slides Using Deep Learning

Colorectal cancer (CRC) is one of the most common types of cancer among men and women. The grading of dysplasia and the detection of adenocarcinoma are important clinical tasks in the diagnosis of CRC and shape the patients' follow-up plans. This study evaluated the feasibility of deep learning models for the classification of colorectal lesions into four classes: benign, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma. To this end, a deep neural network was developed on a training set of 655 whole slide images of digitized colorectal resection slides from a tertiary medical institution; and the network was evaluated on an internal test set of 234 slides, as well as on an external test set of 606 adenocarcinoma slides from The Cancer Genome Atlas database. The model achieved an overall accuracy, sensitivity, and specificity of 95.5%, 91.0%, and 97.1%, respectively, on the internal test set, and an accuracy and sensitivity of 98.5% for adenocarcinoma detection task on the external test set. Results suggest that such deep learning models can potentially assist pathologists in grading colorectal dysplasia, detecting adenocarcinoma, prescreening, and prioritizing the reviewing of suspicious cases to improve the turnaround time for patients with a high risk of CRC. Furthermore, the high sensitivity on the external test set suggests the model's generalizability in detecting colorectal adenocarcinoma on whole slide images across different institutions.

Dysplasia at the Anal Transition Zone after IPAA.

Ileal pouch-anal anastomosis is a popular way of reconstruction the gastrointestinal tract after total proctocolectomy for ulcerative colitis. The pouch-anal anastomosis is usually stapled, which requires the preservation of a small amount of upper anal canal and lower rectum. This includes the anal transition zone (ATZ), a surprisingly small and irregular ring of tissue at and just above the dentate line. The ATZ and rectal cuff is prone to inflammation and neoplasia, particularly in patients who had a colon cancer or dysplasia at the time their large bowel was removed. This high-risk group needs ATZ/rectal cuff surveillance before and after the surgery. Those without colorectal dysplasia preoperatively are at low risk of developing ATZ/rectal cuff dysplasia postoperatively and follow-up can be more relaxed. Treatment of ATZ dysplasia is difficult and may mean mucosectomy, pouch advancement, pouch removal, or a redo pelvic pouch.

Dysregulation of miR-1-3p: An Early Event in Colitis-Associated Dysplasia.

Detection of colorectal dysplasia during surveillance colonoscopy remains the best method of determining risk for colitis-associated colorectal cancer (CAC). miRNAs (miRs) show great promise as tissue-specific biomarkers of neoplasia. The goal of this study was to explore the miR expression profile of precancerous dysplastic lesions in the AOM/DSS mouse model and identify early molecular changes associated with CAC. Epithelial cells were laser-microdissected from the colonic mucosa (inflamed versus dysplastic) of mice with AOM/DSS-induced colitis. A miR signature that can distinguish inflamed non-neoplastic mucosa from dysplasia was identified. Bioinformatic analyses led to the discovery of associated miR gene targets and enriched pathways and supported the construction of a network interaction map. miR-1a-3p was one of the miRs with the highest number of predicted targets, including Cdk6. Interestingly, miR-1a-3p and Cdk6 were down- and up-regulated in dysplastic lesions, respectively. Transfection of HCT116 and RKO cells with miR-1a-3p mimics induced apoptosis and cell cycle arrest in G1, suggesting its biological function. A slight reduction in the level of CDK6 transcripts was also observed in cells transfected with miR-1. These data provide novel insight into the early molecular alterations that accompany the development of CAC and identify a miR signature that represents a promising biomarker for the early detection of colitis-associated dysplasia.

S831 Obesity Is Associated With an Increased Risk of Colorectal Neoplasia in Patients With Inflammatory Bowel Disease

Introduction: Obesity is associated with an increased risk of colorectal neoplasia, but this relationship has not been studied in patients with inflammatory bowel disease (IBD). Both IBD and obesity induce a chronic inflammatory state, so the combination of the two could have an additive or synergistic effect on risk of colorectal neoplasia. Given the increased baseline incidence of dysplasia among IBD patients, identifying modifiable risk factors, such as obesity, could have a significant impact on long term cancer-related outcomes. Methods: We performed a retrospective case-control study of IBD colitis patients at an academic IBD Center between January 2006 and February 2022. Demographic and disease-related data, known risk factors for dysplasia, and median BMI during the follow-up period were obtained. Only patients with at least 5 years of colonoscopy reports were included. A case was defined as any patient with biopsy proven dysplasia—indefinite, low-grade, or high-grade—during the study period. A control was defined as any patient with absence of biopsy-proven dysplasia. Obesity was defined as BMI of 30 or greater. Univariate analysis was performed using T-test for continuous variables and chi-square for categorical variables. Multivariate analysis was performed using logistic regression to model dysplasia risk. Results: 106 cases had biopsy-proven colorectal dysplasia (64 IND, 36 LGD, 10 HGD); 125 controls had no dysplasia. Number of colonoscopies (p < 0.001) IBD subtype ulcerative colitis (p = 0.016), maximum histologic severity (p = 0.127), pseudopolyps (p = 0.162), IBD duration (p = 0.098), sex (p = 0.18), age (p < 0.001), smoking history (p = 0.048), prior dysplasia (p < 0.001), and obesity (p < 0.001) were associated with dysplasia on univariate analysis. On multivariable regression, number of colonoscopies (OR 1.26, 95% CI 1.08 - 1.48, p = 0.004), prior dysplasia (OR 3.98, 95% CI 1.23 - 12.86, p = 0.021), and obesity (OR 2.90, 95% CI 1.21 - 6.95, p = 0.017) were each independently associated with increased dysplasia risk. (Figure) Conclusion: Patients with IBD have an increased risk of colorectal neoplasia, but a variety of comorbid states may exacerbate this risk. Notably, we identified obesity as an independent risk factor for dysplasia. Further research is needed to determine whether this risk functions synergistically with IBD or just as an independent risk factor. Furthermore, targeted weight-loss interventions may reduce the incidence of dysplasia among patients with IBD.Figure 1.: Univariate Analysis and Multivariable Regression of Risk Factors for Dysplasia in IBD Patients.

Crypts in Asymmetric Branching in Patients With Ulcerative Colitis in Remission

Background/Aim: To report the frequency of crypts in asymmetric branching (CAB) in biopsies from all colorectal segments in patients with ulcerative colitis in remission (UCR). Patients and Methods: Biopsies in 100 UC patients were investigated: 50 with UCR and 50 with ongoing long-lasting UC (LLU; i.e., controls). Results: The frequency of CAB was significantly lower in UCR than in LLUC, both in the right colon and left colorectum. CAB frequency was not influenced by two important confounders: the age and sex of patients. Conclusion: CAB is a pathologic aberration of colorectal cryptogenesis evoked by chronic mucosal inflammation. When chronic inflammation waned in UCR, the production of CAB plummeted or ceased. Chronic inflammation and protracted disease-duration in LLUC increase the risk for colorectal dysplasia or carcinoma. Importantly, dysplastic CAB were recently detected in LLUC-associated dysplasia. Whether the abrogation of CAB is instrumental in reducing the neoplastic risk in UCR patients, deserves further investigation.

State-of-the-art surgery for Crohn's disease: Part II-colonic Crohn's disease and associated neoplasms.

Despite advances in medical therapy, surgery continues to play a vital role in the management of Crohn's disease and its complications. Continuing from Part I of this series (small intestine/ileal disease), we focus next on colonic Crohn's disease and associated neoplasms. We will first review the surgical management of medical-refractory Crohn's colitis and its complications and then examine cancer risk, surveillance, and surgical management of Crohn's-associated colorectal dysplasia and malignancy. We conclude with a discussion of restoration of gastrointestinal continuity following colonic surgery for Crohn's disease.

Abstract 1553: miR-1 targets Cdk6 and controls cell cycle progression and apoptosis in colitis-associated dysplasia

Abstract Detection of colorectal dysplasia during surveillance colonoscopy is currently the best method of determining risk of colitis-associated colorectal cancer (CAC). An understanding of the early molecular changes associated with the development of these lesions will inform the identification of new biomarkers for earlier detection. miRNAs (miRs), highly conserved noncoding RNAs, show great promise as stable, tissue-specific biomarkers of neoplasia. We previously identified 12 miRs that are differentially-expressed in colitis-associated dysplasias (flat and polypoid) vs. inflamed colonic mucosa from mice treated with AOM/DSS. miR-1, a putative tumor suppressor, was downregulated in colitis-associated dysplasias. Analysis of the mRNA expression profile of AOM/DSS-induced dysplasias and prediction of the interactions between the miRs and their targets led to the selection of the Cdk6 as the target of miR-1 to be further investigated, based on its: 1) upregulation in AOM/DSS-induced dysplasia; and 2) association with cell cycle progression and inflammatory signaling. The goal of the present study was to validate the predicted interaction between miR-1 and Cdk6 and assess the biological function of miR-1 in vitro. The ability of miR-1 to interact with the 3’UTR of Cdk6 mRNA was assessed using a dual luciferase assay. Co-transfection of HCT116 or RKO colon carcinoma cells with Cdk6-WT and miR-1 mimics led to a significant reduction in relative luciferase activity in both cell lines (30%, p=0.0117 and 47%, p=0.0269; respectively). Transfection with the Cdk6-Mut did not alter relative luciferase activity, confirming the Cdk6 binding site was specific for miR-1. The biological function of miR-1 was assessed in HCT116 and RKO cells reverse-transfected with miR-1 and cel-miR-67 (negative control) for 48 hrs. Apoptosis (AnnexinV+ cells) and cell cycle progression (% of cells in G0/G1, G2/M and S phase) were evaluated by flow cytometry, and proliferation by cell count (Trypan Blue). HCT116 and RKO transfected with the miR-1 mimic exhibited a higher proportion of apoptotic cells than the negative control (30% and 20% increase, p=0.0022 and 0.0013, respectively). Cell cycle analyses revealed the miR-1 mimic induced cell cycle arrest (G0/G1) in both cell lines (p&amp;lt;0.05). In HCT116 cells, this was accompanied by a reduction in the percentage of cells in G2/M (p=0.002) and S (p&amp;lt;0.001) phase. No effect of miR-1 on total cell number was observed. These results demonstrate that Cdk6 is a direct target of miR-1, and suggest that downregulation of this miR in dysplastic lesions contributes to CAC by inducing cell cycle progression and inhibiting apoptosis. These data provide novel insight into the early molecular changes that accompany the development of colitis-associated dysplasia and may serve as biomarkers for early detection of neoplasia. Supported by the Timothy P. and Aurora M. Hughes Fund for Colon Cancer Research. Citation Format: Mariana F. Fragoso, Geysson J. Fernandez, Lisa Vanderveer, Harry S. Cooper, Michael Slifker, Margie L. Clapper. miR-1 targets Cdk6 and controls cell cycle progression and apoptosis in colitis-associated dysplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1553.

Can dysplasia surveillance be better targeted in ulcerative colitis by using faecal calprotectin?

Background: In the inflammatory bowel diseases, chronic inflammation predisposes to dysplasia and colorectal carcinoma, leading to the need of surveillance colonoscopies. The most-used marker of colonic inflammation is faecal calprotectin. Its correlation with endoscopic and histological findings is well-documented. In this study, we evaluated the role of sequential faecal calprotectin measurements in predicting colorectal dysplasia, to identify patients with increased risk of dysplasia or colonic malignancy in ulcerative colitis. Methods: We collected the faecal calprotectin measurements and colorectal histology reports of patients with ulcerative colitis treated in Helsinki University Hospital (Helsinki, Finland) between 2007 and 2017, with a focus on IBD-associated neoplasia, inflammatory activity, and sporadic adenomas. Using the time-weighted AUC of faecal calprotectin as a marker of inflammatory burden, we tested the performance of faecal calprotectin to predict the risk for colorectal neoplasia. Results: In total, 982 patients with ulcerative colitis were included. Of them, 845 had pancolitis and 127 concomitant primary sclerosing cholangitis. Forty-one patients (4%) had IBD-associated colorectal dysplasia and seven (0.7%) developed adenocarcinoma. In patients with constantly elevated faecal calprotectin level (>500 µg/g), colorectal neoplasia was more frequent compared to those with low (<200 µg/g) calprotectin (13% and 4%, p < 0.05). Histological inflammatory activity was also related to more frequent dysplastic changes. Conclusions: Colon dysplasia and adenocarcinoma are more common among ulcerative colitis patients with constantly elevated faecal calprotectin than in patients in remission. The role of inflammatory activity in inducing neoplastic changes in colon is further supported by histology, as histological inflammatory activity correlates with dysplasia.

Advanced endoscopic resection for colorectal dysplasia in inflammatory bowel disease: a meta-analysis.

Background and study aims Little is known about outcomes of advanced endoscopic resection (ER) for patients with inflammatory bowel disease (IBD) with dysplasia. The aim of our meta-analysis was to estimate the safety and efficacy of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for dysplastic lesions in patients with IBD. Methods We performed a systematic review through Jan 2021 to identify studies of IBD with dysplasia that was treated by EMR or ESD. We estimated the pooled rates of complete ER, adverse events, post-ER surgery, and recurrence. Proportions were pooled by random effect models. Results Eleven studies including 506 patients and 610 lesions were included. Mean lesion size was 23 mm. The pooled rate of complete ER was 97.9 % (95 % confidence interval [CI]: 95.3 % to 99.7 %). The pooled rate of endoscopic perforation was 0.8 % (95 % CI:0.1 % to 2.2 %) while bleeding occurred in 1.6 % of patients (95 %CI:0.4 % to 3.3 %). Overall, 6.6 % of patients (95 %CI:3.6 % to 10.2 %) underwent surgery after an ER. Among 471 patients who underwent surveillance, local recurrence occurred in 4.9 % patients (95 % CI:1.0 % to 10.7 %) and metachronous lesions occurred in 7.4 % patients (95 %CI:1.5 % to 16 %) over a median follow-up of 33 months. Metachronous colorectal cancer (CRC) was detected in 0.2 % of patients (95 %CI:0 % to 2.2 %) during the surveillance period. Conclusions Advanced ER is safe and effective in the management of large dysplastic lesions in IBD and warrants consideration as first-line therapy. Although the risk of developing CRC after ER is low, meticulous endoscopic surveillance is crucial to monitor for local or metachronous recurrence of dysplasia.

Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.

Background and study aims In patients with inflammatory bowel disease (IBD), endoscopically visible lesions with distinct borders can be considered for endoscopic resection. The role of endoscopic submucosal dissection (ESD) for these lesions is not well defined because of a paucity of data. We aimed to evaluate the outcomes of colorectal ESD of dysplastic lesions in patients with IBD across centers in the United States. Patients and methods This was a retrospective analysis of consecutive patients with IBD who were referred for ESD of dysplastic colorectal lesions at nine centers. The primary endpoints were the rates of en bloc resection and complete (R0) resection. The secondary endpoints were the rates of adverse events and lesion recurrence. Results A total of 45 dysplastic lesions (median size 30mm, interquartile range [IQR] 23 to 42 mm) in 41 patients were included. Submucosal fibrosis was observed in 73 %. En bloc resection was achieved in 43 of 45 lesions (96 %) and R0 resection in 34 of 45 lesions (76 %). Intraprocedural perforation occurred in one patient (2.4 %) and was treated successfully with clip placement. Delayed bleeding occurred in four patients (9.8 %). No severe intraprocedural bleeding or delayed perforation occurred. During a median follow-up of 18 months (IQR 13 to 37 months), local recurrence occurred in one case (2.6 %). Metachronous lesions were identified in 11 patients (31 %). Conclusions ESD, when performed by experts, is safe and effective for large, dysplastic colorectal lesions in patients with IBD. Despite the high prevalence of submucosal fibrosis, en bloc resection was achieved in nearly all patients with IBD undergoing ESD. Careful endoscopic surveillance is necessary to monitor for local recurrence and metachronous lesions after ESD.

Types of colorectal cancer and dysplasia associated with inflammatory bowel disease

Ulcerative colitis (UC) and Crohn’s disease (CD) are two major inflammatory disorders of the intestinal wall collectively known as inflammatory bowel disease (IBD). Colorectal carcinoma (CRC) is the most significant and grave consequence of IBD and is preceded by dysplasia in majority of the cases. In this review we aim to discuss the various types of dysplasia found in patients with CRC due to IBD. A thorough literature search was conducted in online databases such as PubMed, Google Scholar, from which all studies published in the last ten years were included in this review. The major development in diagnostic procedures and visualization modalities have aided our understanding of dysplasia, which is now known to be the strongest predictor and marker for CRC development. However, the unpredictable behavior and progression of dysplasia still warrants vigilant surveillance. Dysplasia has been classified on histological characteristics using grades of dysplasia from ‘negative for dysplasia’ to ‘high grade dysplasia’. On visibility via an endoscope from ‘visible dysplasia’ to ‘invisible dysplasia’ and macroscopic features of ‘conventional dysplasia’ and ‘non-conventional dysplasia’. No single classification can be utilized to define the stage of dysplasia and more importantly predict its progression and outcome of CRC. Using evidence-based medicine an integrated classification expanding on a management algorithm must be formulated by a panel of experts to steer management of the disease. A multidisciplinary, tailored approach with a strong emphasis on regular and timely surveillance to ensure early detection of CRC can enhance quality of life and patient outcomes.

Danish Society for Gastroenterology and Hepatology’s clinical recommendations for colonoscopic surveillance for colorectal dysplasia and cancer in patients with inflammatory bowel disease

Objectives We aimed to produce clinical recommendations for colonoscopic surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel diseases. Materials and methods The Danish Society for Gastroenterology and Hepatology convened a committee to assess the literature on colorectal cancer in inflammatory bowel diseases and the effectiveness of colonoscopy surveillance, according to the Oxford Centre for Evidence Based Medicine levels of evidence. Results Clinical recommendations for the colonoscopic surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel diseases were produced. These guidelines cover the risk stratification, entry, and follow-up of patients in the colonoscopy programme, the choice of image-enhanced colonoscopy modality, the investigation and treatment of lesions, and the management of special patient populations in the colonoscopy programme. Conclusions Colonoscopic surveillance of inflammatory bowel disease is thought to be associated with a decreased risk of colorectal cancer and colorectal cancer-related mortality. Further evidence regarding the effectiveness of colonoscopic surveillance will contribute to understanding its role in the management of inflammatory bowel diseases. The Danish Society for Gastroenterology and Hepatology clinical guideline will aid gastroenterologists in the risk stratification of patients with inflammatory bowel disease, and the management of colorectal lesions. Gastroenterologists must inform and support patients with inflammatory bowel disease to decide whether to participate in the colonoscopic surveillance programme.

Expression of adipokine ghrelin and ghrelin receptor in human colorectal adenoma and correlation with the grade of dysplasia.

BACKGROUNDGhrelin is an adipokine that plays an important role in energy balance. Expression of ghrelin and ghrelin receptor has been investigated in different tissues and tumors. Studies regarding expression of ghrelin and ghrelin receptor in colorectal tumors are scarce and no data on expression of ghrelin and its receptor in colorectal adenomas has been published. Ghrelin and ghrelin receptor were highly expressed in colon carcinoma cells while expression was decreased in less differentiated tumors, presuming that ghrelin might be important in early phases of tumorigenesis.AIMTo investigate the expression of ghrelin and ghrelin receptor in human colorectal adenomas and adjacent colorectal tissue.METHODSIn this prospective study (conducted from June 2015 until May 2019) we included 92 patients (64 male and 28 female) who underwent polypectomy for colorectal adenomas in the Department of Gastroenterology and Hepatology, “Sestre milosrdnice” Clinical Hospital Center in Zagreb, Croatia. After endoscopic removal of colorectal adenoma, an additional sample of colon mucosa in the proximity of the adenoma was collected for pathohistological analysis. Adenomas were graded according to the stage of dysplasia, and ghrelin and ghrelin receptor expression were determined immunohistochemically in both adenoma and adjacent colon tissue using the polyclonal antibody for ghrelin (ab150514, ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAM Inc, Cambridge, United States). Categorical and nominal variables were described through frequencies and proportions and the difference between specific groups were analyzed with Fisher’s and Fisher-Freeman-Halton’s method respectively. Spearman's rank correlation coefficient was determined for correlation of expression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissue with the grade of adenoma dysplasia.RESULTSAmong 92 patients with colorectal adenoma 43 had adenomas with high-grade dysplasia (46.7%). High expression of ghrelin was 7 times more common in high-grade adenoma compared to low-grade adenomas (13.95% to 2.04%, P = 0.048), while the expression of ghrelin in adjacent colon tissue was low. We found no correlation between ghrelin receptor expression in adenoma and adjacent colon tissue and the grade of colorectal adenoma dysplasia. The most significant correlation was found between ghrelin and ghrelin receptor expression in adenomas with high-grade dysplasia (rho = 0.519, P < 0.001).CONCLUSIONGhrelin and ghrelin receptor are expressed in colorectal adenoma and adjacent tissue with ghrelin expression being more pronounced in high grade dysplasia as a possible consequence of increased local synthesis.

Colorectal Dysplasia and Cancer Surveillance in Ulcerative Colitis.

Ulcerative colitis (UC) is a risk factor for the development of inflammation-associated dysplasia or colitis-associated neoplasia (CAN). This transformation results from chronic inflammation, which induces changes in epithelial proliferation, survival, and migration via the induction of chemokines and cytokines. There are notable differences in genetic mutation profiles between CAN in UC patients and sporadic colorectal cancer in the general population. Colonoscopy is the cornerstone for surveillance and management of dysplasia in these patients. There are several modalities to augment the quality of endoscopy for the better detection of dysplastic or neoplastic lesions, including the use of high-definition white-light exam and image-enhanced colonoscopy, which are described in this review. Clinical practice guidelines regarding surveillance strategies in UC have been put forth by various GI societies, and overall, there is agreement between them except for some differences, which we highlight in this article. These guidelines recommend that endoscopically detected dysplasia, if feasible, should be resected endoscopically. Advanced newer techniques, such as endoscopic mucosal resection and endoscopic submucosal dissection, have been utilized in the treatment of CAN. Surgery has traditionally been the mainstay of treating such advanced lesions, and in cases where endoscopic resection is not feasible, a proctocolectomy, followed by ileal pouch-anal anastomosis, is generally recommended. In this review we summarize the approach to surveillance for cancer and dysplasia in UC. We also highlight management strategies if dysplasia is detected.

Impact of Diagnostic Delay on Disease Course in Pediatric- versus Adult-Onset Patients with Ulcerative Colitis: Data from the Swiss IBD Cohort

Introduction: Given the lack of data, we aimed to assess the impact of the length of diagnostic delay on the natural history of ulcerative colitis (UC) in pediatric (diagnosed <18 years) and adult patients (diagnosed ≥18 years). Methods: Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Diagnostic delay was defined as the interval between the first appearance of UC-related symptoms until diagnosis. Logistic regression modeling evaluated the appearance of the following complications in the long term according to the length of diagnostic delay: colonic dysplasia, colorectal cancer, UC-related hospitalization, colectomy, and extraintestinal manifestations (EIMs). Results: A total of 184 pediatric and 846 adult patients were included. The median diagnostic delay was 4 [IQR 2–7.5] months for the pediatric-onset group and 3 [IQR 2–10] months for the adult-onset group (p = 0.873). In both, pediatric- and adult-onset groups, the length of diagnostic delay at UC diagnosis was not associated with colectomy, UC-related hospitalization, colon dysplasia, and colorectal cancer. EIMs were significantly more prevalent at UC diagnosis in the adult-onset group with long diagnostic delay than in the adult-onset group with short diagnostic delay (p = 0.022). In the long term, the length of diagnostic delay was associated in the adult-onset group with colorectal dysplasia (p = 0.023), EIMs (p < 0.001), and more specifically arthritis/arthralgias (p < 0.001) and ankylosing spondylitis/sacroiliitis (p < 0.001). In the pediatric-onset UC group, the length of diagnostic delay in the long term was associated with arthritis/arthralgias (p = 0.017); however, it was not predictive for colectomy and UC-related hospitalization. Conclusions: As colorectal cancer and EIMs are associated with considerable morbidity and costs, every effort should be made to reduce diagnostic delay in UC patients.

S909 Risk Factors for Colorectal Dysplasia and Colorectal Cancer (CRC) Among Patients With Inflammatory Bowel Disease (IBD) Undergoing Surveillance Colonoscopy in a Tertiary Care Center

Introduction: Patients with IBD are more likely to develop dysplasia and CRC than the general population. We aimed to evaluate risk factors for dysplasia and CRC among patients with IBD undergoing surveillance colonoscopy. Methods: We conducted a retrospective case-control study to evaluate risk factors for colorectal dysplasia/CRC in IBD patients who underwent surveillance colonoscopy in 2010-2020. Cases were patients with dysplasia/CRC found on surveillance colonoscopy and controls were those without. Dysplasia was limited to flat lesions and did not include dysplasia associated lesions/masses. Relevant data obtained from EMR included: age, gender, ethnicity, BMI, smoking status, medication hx, IBD subtype, diagnosis age, disease duration, clinical disease activity, previous IBD related surgery, h/o polyps, dysplasia, or CRC, h/o primary sclerosing cholangitis or extra-intestinal manifestations, family history of IBD, polyps, CRC, and genetic conditions. After summary statistics, logistic regression analysis was performed to examine the association between potential risk factors and incidence of dysplasia or CRC. Rstudio 4.0.2 was used for analysis. Results: 549 subjects were identified from our IBD database with 64 cases and 485 controls. The dysplasia/CRC group had a significantly larger proportion of males (67% vs 48%), patients with UC than CD (69% vs 47%), perianal disease (53% vs 25%), and were more likely to have moderate-severe disease vs remission-mild (36% vs 23%) than the control group. No significant differences were found between groups for the remaining variables. Univariate logistic regression model for each predictor variable of interest revealed statistically significant differences with gender (OR 2.25, 95% CI 1.31-3.97 p=0.004), IBD subtype (OR 2.44, 95% CI 1.42-4.35 p=0.002), disease activity (OR 1.86, 95% CI 1.06-3.21 p=0.028), and perianal disease (OR 3.49, 95% CI 2.05-5.97 p< 0.001). When fitting various multiple logistic regression models and adjusting for the three other variables, disease activity was no longer significant. Conclusion: Our case control study assessing risk factors for colorectal dysplasia or cancer in IBD found that gender, IBD subtype, and perianal disease are perhaps the most significant risk factors for this population. While previous cohorts have noted several of these as potential risk factors, perianal disease has not previously been considered a risk factor for dysplasia/CRC in IBD.

Practice pattern variability among gastroenterologists in colorectal cancer surveillance and management of colorectal dysplasia in inflammatory bowel disease.

There is debate on the best method of colorectal cancer (CRC) surveillance in inflammatory bowel disease (IBD). We aimed to examine how gastroenterologists around the world practice CRC surveillance and manage dysplastic lesions in IBD. A 22-question survey was emailed to gastroenterologists from 34 countries. It included questions on resources for, frequency and mode of CRC surveillance, and management of colorectal dysplasia. Fisher's exact test and logistic regression were used to evaluate the differences among respondents in various domains. There were 217 eligible responses, with most gastroenterologists working in public hospitals (76%), and treating >10 patients with IBD weekly (71%). High-definition white light endoscopy (HDWLE) was available in 93.1% of the centers. The preferred mode of surveillance was HDWLE with dye-spray chromoendoscopy and targeted biopsies (41.2%). Fewer than 50% of physicians reported using chromoendoscopy in >50% of cases, citing time as the limiting factor (73.7%). Of these gastroenterologists 63% infrequently (<25% of cases) performed random biopsies during chromoendoscopy. They would attempt endoscopic mucosal resection for polypoid lesions >10 mm (67.2%), including >20 mm lesions with low grade dysplasia (49.8%), and non-polypoid lesions >10 mm without dysplasia (56.9%). For non-polypoid lesions >20 mm with low- and high-grade dysplasia, referral to expert endoscopists was the preferred option. The preferred method of CRC surveillance was HDWLE with chromoendoscopy and targeted biopsies. Random biopsies were infrequently performed. The uptake of chromoendoscopy for surveillance in practice was low. Physicians varied in their approach in removing endoscopically resectable dysplastic lesions.

Laparoscopic completion proctectomy and pouch with lengthening techniques ‐ a video vignette

Ulcerative Colitis (UC) is a chronic remitting-relapsing inflammatory bowel disorderthat requires surgical treatment in 30% of cases at least. Indications for surgery include refractory disease , colitis-associated colorectal cancer, high-grade dysplasia or stenosis, and septic complications of UC. The recommended intervention consists of restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) 1 .

P348 Perception of cancer risk in inflammatory bowel disease-associated dysplasia and management practice is influenced by colonoscopy experience and workplace affiliation: results of an international clinician survey

Abstract Background A successful inflammatory bowel disease (IBD) surveillance cancer preventative programme requires effective action to be taken when dysplasia is detected. This is the first international cross-sectional study to evaluate current clinician understanding of IBD dysplasia risk, their management practice and adherence to the most recent international guidelines introduced since 2015. Methods A 15-item online survey was disseminated to IBD gastroenterologist and colorectal surgeon members of the British Society of Gastroenterology in June 2019 and the European Crohn’s and Colitis Organisation in February 2020. Results 294 clinicians (93.5% gastroenterologists) from 60 countries responded. A significant proportion indicated not having access to high definition chromoendoscopy IBD surveillance (23%) in their endoscopy units. University hospitals were more likely than non-academic workplaces to provide second expert histopathologist review (67% vs. 46%; p=0.002) and formal multidisciplinary team meeting discussion (73% vs. 52%; p=0.001) of dysplasia cases. Most respondents would advocate endoscopic resection of all visible dysplasia and would refer to a regional specialist therapeutic endoscopist if needed (70%). However, perceptions of 5-year cancer risk associated with endoscopically unresectable low-grade dysplasia (LGD) varied between 0 – 100% (median 20% for visible LGD and median 25% for invisible LGD). Although most (98.4%) would advise a colectomy for endoscopically unresectable visible high-grade dysplasia (HGD), only 34.4% would also advise a colectomy for unresectable visible LGD. Working at a non-academic hospital was predictive of a lower perceived cancer risk with HGD [OR 0.4 (95% CI 0.23-0.95)] and unresectable LGD. Working in a private clinic predicted surveillance preference over colectomy to manage invisible LGD [OR 9.4 (95% CI 1.19-74.1)] and multifocal LGD. Greater surveillance colonoscopy experience predicted a lower preference for continued surveillance over colectomy for invisible LGD [OR 0.41 (95% CI 0.20-0.84)]. Conclusion This study of mainly European gastroenterologists with a sub-specialist interest in IBD has revealed wide variations in colorectal cancer risk perceptions and dysplasia management practices. Clinicians with less IBD surveillance colonoscopy experience and from non-academic centres appeared to have lower cancer risk perceptions and were less likely to advocate colectomy over continued surveillance for high-risk LGD. This study suggests that further education is required to align current management practice with clinical guidelines.