Clinical Characteristics, Associated Malignancies and Management of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease Patients: A Multicentre Retrospective Cohort Study

Abstract

Background and Aims Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. Methods PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. Results In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50–139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7–19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9–5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1–9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39–53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. Conclusions PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.

Effects of Primary Sclerosing Cholangitis on Risks of Cancer and Death in People With Inflammatory Bowel Disease, Based on Sex, Race, and Age

“…The proportion of individuals who developed CRC is similar to that of other populations, 2,4 although differences in followup time may account for the lower frequency of PSC amongst IBD patients compared to some studies. 42 Nonetheless, the proportion of IBD patients who developed PSC in our cohort is within the expected range quoted by contemporary population-based estimates from Spain (0.6%) 43 and Denmark (2.6%). 3 Moreover, the incidence of PSC-IBD in England mirrors that of the Netherlands (0.5 per 100,000), 2 albeit slightly lower than in Finland, Norway and Sweden.…”

Systematic review and meta-analysis: the impact of co-occurring immune-mediated inflammatory diseases on the disease localization and behavior of Crohn’s disease

“…After removing duplicates, irrelevant studies and studies not fulfilling the eligibility criteria, 23 studies were ultimately included in this meta-analysis, including nine retrospective case–control studies, seven prospective cohort studies, six retrospective cohort studies and one population-based cohort study. 16 – 38 A total of 1572 CD patients with IMIDs and 35,043 CD patients without IMIDs were included. Among the IMIDs, CD behavior and localization was most extensively investigated in relation to PSC in a total of eight studies.…”

“…The behavior of CD in relation to co-occurring IMIDs was investigated in 18 studies comprising a total of 847 and 28,601 patients with and without cooccurring IMIDs, respectively. 16,17,19,[21][22][23][24][25]27,[29][30][31][32][33][34][35]37,38 Non-stricturing and non-penetrating disease (B1) was significantly more frequent among patients with co-occurring IMIDs than among patients without IMIDs [RR = 1.30 (95% CI 1.09-1.55), p < 0.01, I 2 = 88%], which was primarily driven by PSC [RR = 1.43 (95% CI 0.97-2.11), p = 0.07, I 2 = 86%] rather than ankylosing spondylitis, celiac disease or erythema nodosum in the subgroup analysis (Figure 3). The high heterogeneity was found to be driven by case-control studies and this subgroup demonstrated significance regarding distribution of B1 [Supplemental Figure 6(b)].…”

Root‐cause analyses of missed opportunities for the diagnosis of colorectal cancer in patients with inflammatory bowel disease

“…Our observation that one‐third of IBD‐associated CRCs were diagnosed in patients who were perceived to be at low‐risk because of limited disease duration or extent, where surveillance had not started, is concerning. Whilst CRC is rarely encountered in the first few years of disease, early‐onset IBD‐related CRCs have been reported, 30 in particular in patients with concomitant primary sclerosing cholangitis 31 . It may be that these patients had active IBD for many years prior to diagnosis.…”

“…Patient not entered/ withdrawn from surveillance (8) • Age/ comorbidity (6) • Patient declined or non-adherent 2Optimal surveillance (11) Suboptimal/no surveillance (31) CRC diagnosed during surveillance…”