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Ulcerative Colitis Patients Inadequately Screened for Colorectal Cancer

By Jill Stein

MADRID, SPAIN -- November 22, 2005 -- Despite the availability of widely accepted recommendations for screening ulcerative colitis (UC) patients for colorectal cancer, gastroenterologists frequently do not implement the guidelines in their clinical practice, according to a presentation here at the 7^th Symposium on Inflammatory Bowel Diseases and Salicylates.

Antoni Obrador, MD, Director of the Gastroenterology Division, Son Dureta Hospital, Palma de Mallorca, Mallorca, Spain, said that several surveys point up shortcomings in colorectal cancer surveillance practices in UC patients vis-à-vis the American Gastroenterology Association (AGA) and American Cancer Society (ACS) recommendations.

"For example, in studies in the US and New Zealand, only about 20 percent of gastroenterologists were able to correctly identify dysplasia," he said during his presentation on November 19^th. "In addition, a Dutch study found that only about one-fourth of gastroenterologists followed established guidelines for colorectal cancer screening in UC patients."

According to the AGA and ACS guidelines, routine screening should begin 8 to 10 years after the onset of pancolitis and 15 to 20 years after the onset of left-sided disease. Also, the length of time between screenings should be reduced with increasing disease duration.

The guidelines also state that two to four random biopsy specimens should be obtained every 10 cm from the entire colon for a total of approximately 40 biopsies per patient per colonoscopy, and additional samples should be taken at any suspicious area.

The guidelines were developed following the accumulation of a large body of evidence that showed a significantly increased risk of colorectal cancer in UC patients.

A meta-analysis found that UC patients have a 2% probability of developing colorectal cancer after 10 years which increases to 8% and 18% after 20 and 30 years, respectively.

Left-sided colitis has a relative risk of 2.8 and pancolitis a relative risk of 14.8. Patients who have UC and primary sclerosing cholangitis have five times the rate of colorectal cancer as UC patients who do not have primary sclerosing cholangitis.

As for why gastroenterologists may not adhere to guidelines, Dr. Obrador said cost may be an important factor. "The US guidelines state that 40 biopsies need to be performed per colonoscopy, and there is no evidence thus far that such an approach is cost-effective," he explained in an interview.

Also, in some countries, there are delays for gastrointestinal exploratory procedures, and colonoscopies may be time-consuming, he added. "So without the evidence supporting their cost-effectiveness, physicians may be less inclined to request such procedures."

Dr. Obrador also pointed out that new endoscopic techniques like chromoendoscopy (in which methylene blue is sprayed over the colonic mucosal area prior to colonoscopy) could allow for improved detection of dysplasia and the use of targeted biopsies instead of random biopsies are obtained with conventional endoscopic techniques.

Elsewhere at the meeting, Eduard Stange, MD, Professor of Medicine, Robert Bosch Hospital, Stuttgart, Germany, pointed out that mesalazines such as Pentasa have been shown to have chemopreventive properties, decreasing the relative risk of colorectal cancer by 81% at doses greater than 1.2 g per day.

There are several possible explanations for the chemopreventive properties with mesalazines, he said. In vitro data have demonstrated a stabilizing effect on micro-satellites, decrease of nuclear factor kB production, inhibition of the production of oxidative radicals, leukotrienes, prostaglandins, and other inflammatory mediators. In vivo data show that mesalazine increases apoptosis in malignant colorectal cancer cells.

Dr. Stange noted, however, that data to date are retrospective and that prospective trials are unlikely, given the large number of patients and long duration of study that would be required.

Finally, he said that currently available data on mesalazine indicate that the number needed to treat (NNT) over 30 years to prevent one colorectal cancer death is 7. Also, large randomized placebo-controlled trials have shown that its safety profile is comparable to placebo, and no increased toxicity in doses up to 4.8 g per day have been identified.

The 7^th Symposium on Inflammatory Bowel Disease and Salicylates was sponsored by Ferring Pharmaceuticals.


SOURCE: Ferring Pharmaceuticals

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