Mortality and extraintestinal cancers in patients with primary sclerosing cholangitis and inflammatory bowel disease

Abstract

Introduction: Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) frequently co-occur. PSC is associated with increased risk for colorectal cancer (CRC). However, whether PSC is associated with increased risk of extraintestinal cancers or affects mortality in an IBD cohort has not been examined previously. Methods: In a multi-institutional IBD cohort of IBD, we established a diagnosis of PSC using a novel algorithm incorporating narrative and codified data with high positive and negative predictive value. Our primary outcome was occurrence of extraintestinal and digestive tract cancers. Mortality was determined through monthly linkage to the social security master death index. Results: In our cohort of 5,506 patients with CD and 5,522 patients with UC, a diagnosis of PSC was established in 224 patients (2%). Patients with IBD-PSC were younger and more likely to be male compared to IBD patients without PSC; three-quarters had UC. IBD-PSC patients had significantly increased overall risk of cancers compared to patients without PSC (OR 4.36, 95% CI 2.99 – 6.37). Analysis of specific cancer types revealed that a statistically significant excess risk for digestive tract cancer (OR 10.40, 95% CI 6.86 – 15.76), pancreatic cancer (OR 11.22, 95% CI 4.11 – 30.62), colorectal cancer (OR 5.00, 95% CI 2.80 – 8.95), and cholangiocarcinoma (OR 55.31, 95% CI 22.20 – 137.80) but not for other solid organ or hematologic malignancies. Conclusions: PSC is associated with increased risk of colorectal and pancreatobiliary cancer but not with excess risk of other solid organ cancers.

Colonoscopy Is Associated With a Reduced Risk for Colon Cancer and Mortality in Patients With Inflammatory Bowel Diseases

“…In a previous study from our group, we confirmed the high positive predictive value of this diagnostic code in our EMR, consistent with published literature 24, 26–28 . Our main predictor of interest was undergoing a colonoscopy within 36 months prior to the first date of CRC diagnosis (for cases) or end of follow-up (for non-cases).…”

“…Among patients who did not have CRC, we required at least 3 years of care in our system, no colectomy during this period, and counted only colonoscopies occurring within 3 years of the date of last visit in our system to ensure a similar time frame of reference as the CRC group. Mortality was determined by linkage to the social security death index with updates every month as described previously 24 .…”

Pancreatic cancer: current understanding of molecular and genetic aetiologies

“…For example, patients with pancreatic cancer are more likely to be Helicobacter pylori positive (OR 2.78) 18. Patients with inflammatory bowel disease (IBD)—both Crohn's disease and ulcerative colitis—have an increased lifetime risk of pancreatic cancer (OR 11.22) 19. This risk is further increased in patients with IBD with associated primary sclerosing cholangitis 19.…”

“…Patients with inflammatory bowel disease (IBD)—both Crohn's disease and ulcerative colitis—have an increased lifetime risk of pancreatic cancer (OR 11.22) 19. This risk is further increased in patients with IBD with associated primary sclerosing cholangitis 19. Furthermore, patients who have hepatitis B have an increased risk of pancreatic cancer (OR 1.50)20 and hepatitis C virus may also cause an increased risk (HR 1.6)21 although the association is less clear.…”

Therapy of Primary Sclerosing Cholangitis - Today and Tomorrow

“…Various malignancies have been reported to be associated with PSC such as cholangiocellular (CCA) [9,10] , colorectal [10] , gallbladder [11] , pancreatic [8,12] , and hepatocellular cancer [13] , although the association of later 2 may not be strong and has been discussed controversially [14,15] . CCA represents the most frequent malignancy and is the mostly feared malignant complication of PSC.…”