Colorectal Cancer In Ulcerative Colitis Patients Research Articles

P1171 The impact of biological and small molecule therapy on time to colonic resection and cancer rates in patients with Ulcerative Colitis

Abstract Background The expanding medical armamentarium in ulcerative colitis (UC) has contributed to increased control of inflammation. However, simultaneously, postponed colonic resection with an accumulative inflammatory burden might lead to an increased risk of CRC. Recent studies have reported conflicting results regarding the incidence of colorectal cancer (CRC) in UC patients. Aim To analyse the impact of advanced medical therapies (defined as biologicals and small molecules) on time to colonic resection and risk of CRC in UC patients. Methods Consecutive patients ≥18 years with established UC who underwent colonic resection between January 2003 and October 2022 at the Academic Medical Centre Amsterdam or the University Hospital Leuven were included. Primary outcomes were time to colonic resection and CRC rate in colonic specimens, compared between four time periods: P1 (2003-2007), P2 (2008-2012), P3 (2013-2017) and P4 (2018-2022). Secondary outcomes were the effect of advanced medical therapy on time to resection, cancer stage and risk of CRC. CRC was staged according to the AJCC TNM classification (advanced cancer defined as T3/T4, N1/2 or M1). Results A total of 716 patients were included. The usage of advanced medical therapies prior to surgery increased from 38.2% in P1 to 90.2% in P4 (p<0.001). However, this did not result in an increased time to colonic resection (P1: 7 years (2-12) vs P2: 6 years (2-14) vs P3: 7 years (3-14) vs P4: 7 years (2-14), p=0.94). CRC was diagnosed in 72 (10.1%) patients, and this incidence did also not change over time. Time to resection was significantly longer (median 18 years, IQR 10-24) in CRC patients compared to the overall cohort. The majority of CRC patients (64.8%) were diagnosed with advanced cancer, which did not decrease over time. Patients using advanced medical therapies had significantly shorter follow-up compared to therapy-naïve patients (6 years vs. 10 years, p<0.001), which resulted in a decreased risk of CRC (OR 0.17, p=<0.001). However, the finding of an incidental carcinoma rate (i.e. not preoperatively diagnosed) in this group was 18% whereas this was only 4% in patients without advanced medical therapy (p=0.08). Moreover, the incidence of advanced CRC was numerically higher in UC patients who received ≥2 therapies (83.3% vs 61.0%, p=0.14). Conclusion This study demonstrated that in the last two decades, the increased usage of advanced medical therapies did not result in an increased time to resection, nor in a decreased CRC rate in UC patients undergoing colonic resection. A higher incidence of incidental and advanced cancers was seen in patients with ≥2 therapies. Therefore, care should be taken with improved tailored surveillance in this group.

P662 Colorectal Cancer in Patients with Ulcerative Colitis: A National Cohort Study between 1991–2020

Abstract Background Studies on the colorectal cancer (CRC) risk in patients with ulcerative colitis (UC) show conflicting results. The aim of the current study was to assess if there is an indication shift for surgery in patients with UC from refractory disease to malignant degeneration over the last 3 decades. Methods From the nationwide Dutch Pathology Registry (PALGA), pathology excerpts from all patients with histologically confirmed UC who underwent a colorectal resection for all indications between January 1st, 1991 and November 12th, 2020 were included. The primary outcome was the CRC rate in the colon specimens. Outcomes were compared between 3 time periods (P1: 1991–2000, P2: 2001–2010, P3: 2011–2020). Results Overall, 6,094 UC patients were included of which 5,026 underwent a (procto)colectomy and 1,068 a segmental resection. In 1,031 (16.9%) patients, pathological examination demonstrated CRC after a median disease duration of 11 years [IQR 3.0–19.0]. The CRC rate in the colectomy specimen increased from 11.3% in P1, to 16.1% in P2, to 22.8% in P3 (p-trend <0.001). Compared to patients in P1, patients in P2 and P3 had a longer disease duration before resection (4 years [IQR 0.0–9.0] vs. 10 years [IQR 3.0–16.0] vs. 17 years [IQR 7.0–23.0], p<0.001). The proportion of patients diagnosed with advanced disease (pT3/T4) (P1: 61.2% vs. P2: 65.2% vs. P3: 62.4%, respectively, p=0.633) and lymph node metastasis (P1: 33.0% vs. P2: 41.9% vs. P3: 38.2%, respectively, p=0.113) did not decrease over time. Conclusion This nationwide pathology study demonstrated an increased surgical indication rate for CRC in UC patients over the last 3 decades. We hypothesize that the expanding therapeutic armamentarium for UC likely leads to exhausting medical options and hence postponed colectomy. This however, might be at the expense of increased risk of CRC in the long term. Despite the introduction of surveillance programs, the incidence of advanced colon carcinoma remains high.

Long-term incidence of dysplasia and colorectal cancer in an ulcerative colitis population-based cohort.

Ulcerative colitis (UC) is a risk factor in developing colorectal cancer (CRC). Surveillance programmes aim to identify premalignant lesions to facilitate improved treatment outcomes. Recent studies have suggested that the risk of CRC in UC has decreased. This study aims to characterize the risk of CRC in UC in a population-based New Zealand cohort. All patients in the Canterbury Inflammatory Bowel Disease Study, a comprehensive population-based cohort, were reviewed and cases of dysplasia and CRC identified. Demographic data and risk factors were assessed and standardized incidence ratios (SIRs) calculated comparing with the national population. A total of 518 UC cases were analysed (46.3% female). Median follow-up was 17.5 years (interquartile range 12.2-25.1 years). Neoplasia developed in 42 (8.1%) patients, 14 (2.7%) of whom had CRC. The mean age at CRC diagnosis was 63.3 years, and mean duration with UC before CRC 18.4 years (0-36.8 years). The total incidence rate was 1.35/1000 person-year duration (95% confidence interval 0.74-2.27). The age-adjusted SIR was 1.74 (95% confidence interval 1.03-2.93) compared to the New Zealand population. Risk factors for any dysplasia included disease extent and male gender. In this population-based cohort with long-term follow-up, the SIR of CRC in UC patients was significantly lower than the initial epidemiological studies although similar to more recent studies. This increased risk still justifies ongoing screening in the UC population.

Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis.

Background Ulcerative colitis (UC) patients have an increased risk for the development of colorectal cancer (CRC). Our aim was to assess the risk of CRC in UC patients compared with disease extent, disease duration, and geographic variation. Methods In this systematic review and meta-analysis, we searched PubMed, scientific meetings, and the bibliographies of identified articles, with English language restrictions for studies published from 1988 to 2018, and assessed the risk of CRC in UC patients. Patients with Crohn's disease, family history of CRC, and colorectal adenomatous polyp (CAP) were excluded from this research. The study was registered with PROSPERO, number CRD42018102213. Findings We included 58 studies that included 267566 UC patients. Extensive UC and left-sided UC had a higher risk of CRC than proctitis UC. Geography also played a role in UC-associated CRC development. The time of malignant transformation in Asian UC patients started after 10-20 years of this disease duration. North American UC-associated CRC patients significantly increased in more than 30 years of this disease duration. Conclusion In a systematic review of the literature, we found that disease extent, disease duration, and geography were strong, independent risk factors in UC-associated CRC development.

Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis Frequently Have Subclinical Inflammation in the Proximal Colon

Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) have a high risk of colonic neoplasia. Neoplasia frequently develops in the proximal colon in patients with PSC. Histologic inflammation is an independent risk factor for the development of neoplasia; we investigated whether patients with UC and PSC have more subclinical disease activity than patients with UC alone. We performed a retrospective analysis of data from 143 patients (205 examinations) with ulcerative pancolitis who were in clinical remission and treated at a tertiary medical center from May 2011 through May 2016. Endoscopic and histologic activity were compared between patients with PSC (from 36 examinations) and without PSC (from 169 examinations). Disease activity was scored per colonic segment using a modified Mayo endoscopic subscore and histologic assessment. In each colonic segment, differences in disease activity and the degree of discordance between endoscopic and histologic inflammation among UC patients with and without PSC were compared. Patients with UC-PSC had significantly more subclinical endoscopic (odds ratio [OR], 4.21; 95% CI, 1.67-10.63) and histologic activity (OR, 5.13; 95% CI, 2.25-11.68) in the right colon, as well as greater degree of histologic than endoscopic inflammation in the proximal colon (OR, 3.14, 95% CI, 1.24-7.97), compared with patients without PSC. Patients with UC-PSC had significantly less histologic activity in the rectum on multivariate analysis (OR, 0.24; 95% CI, 0.08-0.72). Patients with UC and PSC who are in clinical remission are significantly more likely to have endoscopic and histologic inflammation in the right colon than patients with UC without PSC. Our findings provide insight into cause of colorectal cancer in UC patients with PSC.

Patients with Endoscopically Visible Polypoid Adenomatous Lesions Within the Extent of Ulcerative Colitis Have an Increased Risk of Colorectal Cancer Despite Endoscopic Resection.

Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Few studies have looked at long-term outcomes of endoscopically visible adenomatous lesions removed by endoscopic resection in these patients. We aimed to assess the risk of developing CRC in UC patients with adenomatous lesions that develop within the segment of colitis compared to the remainder of an ulcerative colitis cohort. We identified patients with a confirmed histological diagnosis of UC from 1991 to 2004 and noted outcomes till June 2011. The Kaplan-Meier method was used to estimate cumulative probability of subsequent CRC. Factors associated with risk of CRC were assessed in a Cox proportional hazards model. Twenty-nine of 301 patients with UC had adenomatous lesions noted within the segment of colitis. The crude incidence rate of developing colon cancer in patients with UC was 2.45 (95% CI 1.06-4.83) per 1000 PYD and in those with UC and polypoid adenomas within the extent of inflammation was 11.07 (95% CI 3.59-25.83) per 1000 PYD. Adjusted hazards ratio of developing CRC on follow-up in UC patients with polypoid dysplastic adenomatous lesions within the extent of inflammation was 4.0 (95% CI 1.3-12.4). The risk of developing CRC is significantly higher in UC patients with polypoid adenomatous lesions, within the extent of inflammation, despite endoscopic resection. Patients and physicians should take the increased risk into consideration during follow-up of these patients.

Low-grade dysplasia in ulcerative colitis: risk factors for developing high-grade dysplasia or colorectal cancer.

OBJECTIVES:The aim of this study was to identify risk factors associated with development of high-grade dysplasia (HGD) or colorectal cancer (CRC) in ulcerative colitis (UC) patients diagnosed with low-grade dysplasia (LGD).METHODS:Patients with histologically confirmed extensive UC, who were diagnosed with LGD between 1993 and 2012 at St Mark's Hospital, were identified and followed up to 1 July 2013. Demographic, endoscopic, and histological data were collected and correlated with the development of HGD or CRC.RESULTS:A total of 172 patients were followed for a median of 48 months from the date of initial LGD diagnosis (interquartile range (IQR), 15–87 months). Overall, 33 patients developed HGD or CRC (19.1% of study population; 20 CRCs) during study period. Multivariate Cox proportional hazard analysis revealed that macroscopically non-polypoid (hazard ratio (HR), 8.6; 95% confidence interval (CI), 3.0–24.8; P<0.001) or invisible (HR, 4.1; 95% CI, 1.3–13.4; P=0.02) dysplasia, dysplastic lesions ≥1 cm in size (HR, 3.8; 95% CI, 1.5–13.4; P=0.01), and a previous history of “indefinite for dysplasia” (HR, 2.8; 95% CI, 1.2–6.5; P=0.01) were significant contributory factors for HGD or CRC development. Multifocal dysplasia (HR, 3.9; 95% CI, 1.9–7.8; P<0.001), metachronous dysplasia (HR, 3.5; 95% CI, 1.6–7.5; P=0.001), or a colonic stricture (HR, 7.4; 95% CI, 2.5–22.1; P<0.001) showed only univariate correlation to development of HGD or CRC.CONCLUSIONS:Lesions that are non-polypoid or endoscopically invisible, large (≥1 cm), or preceded by indefinite dysplasia are independent risk factors for developing HGD or CRC in UC patients diagnosed with LGD.

Su1653 Low-Grade Dysplasia in Ulcerative Colitis: Shape and Size of the Lesion, and Previous Episode of Indefinite Dysplasia Are Important Predictors for Progression to High-grade Dysplasia or Cancer

One of the most challenging aspects of managing low-grade dysplasia (LGD) in ulcerative colitis (UC) is the identification of patients who will progress to high-grade dysplasia (HGD) or colorectal cancer (CRC). The aim of this study was to identify risk factors associated with progression to HGD or CRC in UC patients diagnosed with LGD.

Mechanisms of Immune Signaling in Colitis-Associated Cancer

The inflammatory bowel diseases ulcerative colitis and Crohn’s disease are associated with an increased risk for the development of colorectal cancer. During recent years, several immune signaling pathways have been linked to colitis-associated cancer (CAC), largely owing to the availability of suitable preclinical models. Among these, chronic intestinal inflammation has been shown to support tumor initiation through oxidative stress–induced mutations. A proinflammatory microenvironment that develops, possibly as a result of defective intestinal barrier function and host–microbial interactions, enables tumor promotion. Several molecular pathways such as tumor necrosis factor/nuclear factor-κB or interleukin 6/signal transducer and activator of transcription 3 signaling have been identified as important contributors to CAC development and could be promising therapeutic targets for the prevention and treatment of CAC.

Systematic review with meta‐analysis: the declining risk of colorectal cancer in ulcerative colitis

Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC); however, the magnitude of this effect is open to debate. To assess the risk of CRC in UC patients by systematic review and meta-analysis. A systematic literature search was performed up to November 2013. We selected studies describing the incidence and prevalence of CRC in patients with UC. Articles were assessed for quality using the Newcastle-Ottawa Scale. Cumulative incidence and incidence rates of CRC were combined and analysed using the generic inverse variance method. Sub-analyses were performed to identify factors associated with an increased risk of developing CRC. A total of 81 studies (181 923 patients) met the inclusion criteria. The incidence rate of CRC in patients with UC was 1.58 per 1000 patient-years (py) [95% confidence interval (CI), 1.39–1.76]. Results were heterogeneous (I2 = 81–89%). The incidence rate was 4.02/1000 py (95%CI = 2.74–5.31) in studies that only included patients with extensive colitis, and 1.24/1000 py (95%CI = 1.01–1.47) in population-based studies. The incidence rate was 0.91/1000 py (95%CI = 0.61–1.2) in the first decade of disease, 4.07/1000 py (95%CI = 2.58–5.56) in the second, and 4.55/1000 py (95%CI = 2.64–6.46) in the third. The incidence rate decreased from 4.29/1000 py in the studies published in the 1950s to 1.21/1000 py in studies published in the last decade. The risk of patients with ulcerative colitis developing colorectal cancer has decreased steadily over the last six decades, but the extent and duration of the disease increase this risk.

Covering the Cover

Covering the Cover

Does Colorectal Cancer in Ulcerative Colitis Patients Constitute a Risk for Chemotherapy Refractoriness? A Systemic Approach by Detailed Analysis via the Electronic Tumor Base Documentation System

Background: Ulcerative colitis (UC) patients may develop colorectal cancer (CRC), especially with pancolitis and longer UC duration. The question whether CRC with underlying UC has a dismal prognosis remains unsettled. Patients and Methods: We performed an electronic tumor base documentation (eTBD) search of CRC and UC patients at our department to address whether (1) CRC prognosis is impaired and (2) defined risks can be determined. Results: With the inclusion of an index patient with UC and unresponsive CRC, 20 additional patients were identified via eTBD. Chemotherapy response was less substantial, with complete response or stable disease in 3 patients each, but rapidly progressing or refractory disease in 15/21 patients. 12 out of the 21 patients died. Our hazard ratio analysis revealed International Union against Cancer (UICC) stage IV and III disease, grade 3 tumors, longer latency from UC to CRC and age >60 years as potential risks. Median progression-free survival and overall survival were 48 and 82 months, respectively. Time from tumor dissemination to death was 10 months. Conclusions: The prognosis of CRC in UC patients is not necessarily impaired, albeit chemotherapy response with disseminated disease may be unfavorable. Our data should be enlarged by subsequent analyses to better elucidate whether response in UC and CRC is more challenging and defined risks can be confirmed.

Paediatric inflammatory bowel disease during a 44-year period in Copenhagen County: occurrence, course and prognosis – a population-based study from the Danish Crohn Colitis Database

To describe the development in incidence, disease localization, activity, surgery and prognosis in two Danish paediatric population-based inflammatory bowel disease (IBD) cohorts comparing the time periods 1962-1987 (period I) and 1998-2006 (period II). Incident IBD patients below 15 years of age were included. Disease localization was classified according to the Montreal classification for ulcerative colitis (UC) patients and into small bowel, large bowel and small and large bowel combined for Crohn's disease (CD) patients. Disease activity and surgery in the first 2 years after diagnosis were assessed. Standardized cancer incidence rates and standardized mortality rates were calculated. One hundred and nineteen IBD patients (77 UC and 42 CD) were included. Comparing periods II and I, the incidence rate ratios were 0.81 [95% confidence interval (CI): 0.5-1.4] and 15.6 (95% CI: 7.5-32.7) in UC and CD, respectively. The number of UC patients with extensive disease (E3) increased from period I to II (46.7 vs. 94.1%, P<0.001). No colectomies were performed in UC patients in period II compared with nine in period I (P = 0.13) within the first 2 years after diagnosis. For patients diagnosed in period I, the standardized cancer incidence rate for UC was 37.9 (95% CI: 4.6-136.7) after a median follow-up period of 26 years. We found a significant 15-fold increase in the incidence of CD and a significant increase in the number of UC patients with extensive disease in period II compared with period I. After a median follow-up time of 26 years, a possible increased risk of colorectal cancer in UC patients was detected.

Clinical study of the relationship between inflammatory bowel diseases and colorectal neoplasms

To investigate the incidence of colorectal cancer in inflammatory bowel disease (IBD) patients and its risk factors. Data on 513 patients in the last 10 years from Ruijin Hospital were collected. Their medical histories were put in database and analyzed including their socio-demographic features, pathogenetic conditions, diagnostic methods, possible related risk factors, treatment and outcome. Among the 513 were 242 with ulcerative colitis (UC), among whom four patients developed cancers and four had precancerous lesions. None of the 271 CD patients developed cancer. The incidence of both cancer and precancerosis in the UC patients was 1.65%. Through multifactorial logistic regression analysis, loss of weight, other disease complications and frequent relapses were proved to be the most probable risk factors. The incidence of IBD has kept on rising in recent years. Clinically, UC patients have more probability of developing colorectal cancer than CD patients. The main risk factors of developing colorectal cancer in UC patients are frequent relapses, weight loss and other complications.

Aminosalicylate Therapy in the Prevention of Dysplasia and Colorectal Cancer in Ulcerative Colitis

Aminosalicylates have been suggested as chemopreventive agents for colorectal cancer (CRC) in ulcerative colitis (UC). We studied the effect of aminosalicylate use on dysplasia and CRC risk in chronic UC. UC patients with dysplasia or CRC were matched with controls by disease duration, extent, and age at diagnosis. The total amount of aminosalicylates over the duration of the disease and the mean daily amount of drug was calculated. Conditional logistic regression was used to examine the relationship of aminosalicylates to the risk of neoplasia; potential confounders were controlled in a multivariable model. Twenty-six cases (8 CRC, 18 dysplasia) were matched with 96 controls. Cases and controls were similar in age (median, 43 vs 42.5 y), age at diagnosis of UC (median, 29.5 vs 30.5 y), duration of UC (median, 11.5 vs 9 y), and extent of disease (58% pancolitis), sex, family history of UC, history of primary sclerosing cholangitis, and smoking history. Cases were more likely to have a family history of CRC than controls (27% of cases, 9% of controls, P = .036). Conditional logistic regression adjusted for disease duration, age at diagnosis, and family history of CRC showed that aminosalicylate use of 1.2 g/day or more was associated with a 72% reduction in the odds of dysplasia/CRC (odds ratio, 0.28; 95% confidence interval, 0.09-0.85). As the total dose of aminosalicylates increased, the odds of dysplasia/CRC decreased (P = .056). This case-control study shows a significant risk reduction of dysplasia and CRC in UC patients exposed to aminosalicylate therapy.

This Month in Gastroenterology

This Month in Gastroenterology

Difference in Ulex europaeus agglutinin I–binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis

Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay ( P < .05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

The color of dysplasia in ulcerative colitis

The color of dysplasia in ulcerative colitis