Institutionen Södersjukhuset / Karolinska Institutet, Stockholm Söder Hospital
Abstract
The association between ulcerative colitis (UC) and cancer in a defined
geographical region in Sweden was analyzed. UC patients have an increased
overall risk of cancer of 40%, mainly due not only to the well-known
increased risk of colorectal cancer (CRC) but also to the risk of
hepatobiliary cancer associated with primary sclerosing cholangitis
(PSC). The overall risk is partly counterbalanced by a decreased risk of
lung cancer, reflecting the observation that there is a larger proportion
of nonand ex- smokers among UC patients than among the general
population.
A 23-year prospective study to evaluate the safety, reliability, and
efficacy of a prospective colonoscopic surveillance program in
long-standing UC was analyzed, and estimates of the cumulative risks of
developing histologic dysplasia and gross chromosomal abnormalities (DNA
aneuploidy) were calculated. A theoretical modified algorithm for
separation of low-risk from high-risk cancerprone UC patients early was
designed, in order to minimize surveillance efforts and costs. The
cumulative risk of having >= low-grade dysplasia at least once after 25
years of disease was 16%, and for DNA aneuploidy it was 29%. Patients
with three consecutively negative colonoscopies could be put into a low-
risk group in which surveillance could be decreased to colonoscopy every
fifth year. Combining histopathology with DNA analyses allows a schedule
sufficiently accurate for selection of high-risk patients and also has
the potential to reduce the number of colonoscopies by 30%. Colonoscopic
surveillance with biopsies for histological assessment and DNA flow
cytometry is a reliable and safe way to select high-risk UC patients for
prophylactic colectomy.
The reproducibility of DNA aneuploidy from one examination to another in
a surveillance program for UC was determined, as was the topographical
correlation between the aneuploid peaks and histological dysplasia in the
colon and rectum. Detection of DNA aneuploidy in UC patients is
persistent and reproducible and is closely related to and often precedes
histological dysplasia. Widespread aneuploidy indicates that the entire
colorectal mucosa is at increased risk of malignant transformation.
The relationship between the mucin-associated carbohydrate antigen
Sialyl-Tn (STn) and DNA aneuploidy with respect to topographic and
temporal distribution in the colon and to areas with dysplasia was
analyzed. STn antigen and DNA aneuploidy are independent markers of
neoplastic transformation. Determination of STn expression may complement
dysplasia and DNA aneuploidy in identifying risk for colonic neoplasia in
UC.
To analyze the impact of colonoscopic surveillance on CRC mortality in
patients with UC, a nested case-control study was performed using
observational data from a large population-based cohort of patients with
UC. Two out of 40 cases and 18 out of 102 controls had received at least
one surveillance colonoscopy [relative risk (RR)=0.29, 95% confidence
interval (CI) 0.06-1.31 ]. Twelve of the controls but only one of the
cases had been subjected to two or more surveillance colonoscopies
(RR=0.22, 95% CI 0.03-1.74), thus indicating a protective dose-response
relationship. Colonoscopic surveillance may be associated with a
decreased risk of death from colorectal cancer in patients with long-
standing ulcerative colitis