ABSTRACT
Patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Risk factors are extent and severity of colonic inflammation, concurrent primary sclerosing cholangitis, and a positive family history of sporadic CRC. The chromosomal instability, microsatellite instability and hypermethylation pathways form the molecular background of IBD-related carcinogenesis, which is not different from sporadic CRC. The dysplasia-carcinoma sequence of IBD-related colorectal carcinogenesis makes patients suitable for endoscopic surveillance. In the future, new molecular biomarkers and endoscopic techniques may improve early detection of precursor lesions of IBD-related CRC. The potential of aminosalicylates and ursodeoxycholic acid as chemopreventive agents needs to be studied in randomized clinical trials. Patients with IBD who are being treated with thiopurines have a slightly increased risk of developing lymphoproliferative disorders, whereas patients with small bowel Crohn's disease have a high relative risk and a small absolute risk of developing small bowel adenocarcinoma.
Subject(s)
Colorectal Neoplasms/etiology , Inflammatory Bowel Diseases/complications , Lymphoma/etiology , Adenocarcinoma/etiology , Antineoplastic Agents/therapeutic use , Chromosomal Instability , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , CpG Islands/physiology , DNA Methylation , Disease Progression , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/genetics , Intestinal Neoplasms/etiology , Lymphoma/prevention & control , Microsatellite Instability , Risk FactorsABSTRACT
BACKGROUND: Patients with inflammatory bowel disease (IBD) and concurrent primary sclerosing cholangitis (PSC) have a higher risk of developing colorectal cancer (CRC) than IBD patients without PSC. The aim of this study was to investigate potential clinical differences between patients with CRC in IBD and those with CRC in IBD and PSC, as this may lead to improved knowledge of underlying pathophysiological mechanisms of CRC development. METHODS: The retrospective study from 1980-2006 involved 7 Dutch university medical centers. Clinical data were retrieved from cases identified using the national pathology database (PALGA). RESULTS: In total, 27 IBD-CRC patients with PSC (70% male) and 127 IBD-CRC patients without PSC (59% male) were included. CRC-related mortality was not different between groups (30% versus 19%, P = 0.32); however, survival for cases with PSC after diagnosing CRC was lower (5-year survival: 40% versus 75% P = 0.001). Right-sided tumors were more prevalent in the PSC group (67% versus 36%, P = 0.006); adjusted for age, sex, and extent of IBD, this difference remained significant (odds ratio: 4.8, 95% confidence interval [CI] 2.0-11.8). In addition, tumors in individuals with PSC were significantly more advanced. CONCLUSIONS: The right colon is the predilection site for development of colonic malignancies in patients with PSC and IBD. When such patients are diagnosed with cancer they tend to have more advanced tumors than patients with IBD without concurrent PSC, and the overall prognosis is worse. Furthermore, the higher frequency of right-sided tumors in patients with PSC suggests a different pathogenesis between patients with PSC and IBD and those with IBD alone.
Subject(s)
Cholangitis, Sclerosing/complications , Colorectal Neoplasms/etiology , Inflammatory Bowel Diseases/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cholangitis, Sclerosing/diagnosis , Colorectal Neoplasms/diagnosis , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Inflammatory Bowel Diseases/diagnosis , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Young AdultABSTRACT
BACKGROUND: Development of colitis-associated colorectal cancer is an important clinical problem in patients with colonic inflammatory bowel disease (IBD). British and American guidelines recommend to start surveillance after a disease duration of 8-10 or 15-20 years for patients with extensive or left-sided colitis, respectively. AIM: To assess the evidence level of current surveillance strategies. METHODS: A PubMed-based literature search using the search terms inflammatory bowel disease, ulcerative colitis, Crohn's disease, dysplasia, colorectal cancer and surveillance was performed. RESULTS: Low-grade and high-grade dysplastic lesions progress to cancer in a high percentage of patients. Furthermore, concurrent cancer is found in approximately one-third of the patients with colonic dysplasia. Low-level evidence showing reduced colorectal cancer-related mortality in patients who were undergoing surveillance is available. Patients with concomitant primary sclerosing cholangitis form a subgroup of IBD patients with an even higher risk of colorectal neoplasia. CONCLUSIONS: Colonic surveillance prolongs life expectancy of patients with long-lasting IBD.
