Familial adenomatous polyposis is an inherited colorectal cancer syndrome characterized by the presence of multiple adenomatous colorectal polyps.
Molecular studies have revealed that germline mutations in the APC gene are the underlying cause of the disease.
The NSAID sulindac has been shown to reduce the number of colorectal adenomas.
However, most sulindac trials in the large bowel have focused on the distal colon and relatively little is known about its effect on the proximal colon. Moreover, it is unknown whether the site of the APC mutation affects the efficacy of sulindac.
A study reported in the August issue of the journal Diseases of the Colon and Rectum has now investigated whether there are regional differences in the effect of sulindac on the colon and also whether response to sulindac is dependent on the site of mutation in the APC gene.
The open prospective study involved 17 patients with familial adenomatous polyposis were treated with 300 mg oral sulindac daily for 4 months, followed by a washout period of 6 months.
Ten of the patients had an intact colon and seven had rectal stumps only.
The number, size, and the degree of the dysplasia of the adenomas were evaluated by colonoscopy at entry, end of treatment, and end of study.
The research group, comprising teams from universities in Switzerland and Australia, observed a statistically significant decrease in the overall number of adenomas following treatment with sulindac.
|Sulindac reduced the overall number of adenomas|
|Diseases of the Colon and Rectum|
After cessation of sulindac administration, the number of adenomas was seen to increase, but remained significantly lower than the values observed at baseline.
In the 10 patients with intact colons, adenomas decreased by sevenfold in the proximal colon and twofold in the distal colon. The size of adenomas and the grade of dysplasia also decreased.
NO correlation could be seen between the APC mutation site and the response to treatment.
Dr Irene Guldenschuh, summarizing the research group's findings on behalf of her colleagues said, "The data indicate that sulindac reduces the number of adenomas in the entire colon and that the effect seems to be more pronounced in the proximal colon."