Franca Bianchini

Rectal proliferation and polyp occurrence in patients with familial adenomatous polyposis after sulindac treatment

BACKGROUND/AIMS Sulindac, a nonsteroidal anti-inflammatory drug (NSAID), decreases the occurrence of polyps in patients with familial adenomatous polyposis (FAP). The effects of colectomy with ileorectal anastomosis (IRA) and sulindac treatment on rectal mucosa proliferation and polyp occurrence were examined in patients with FAP. METHODS The number and size of rectal polyps were measured with colonoscopy. The labeling index, the percentage of labeled cells per crypt compartment, was assessed in rectal biopsy specimens with [3H]thymidine incorporation and autoradiography in 6 non-IRA and 14 IRA patients before and after treatment with 200 mg of sulindac/day for 60 days. RESULTS The IRA patients had a lower labeling index and a decrease in the percentage of labeled cells in the upper compartment of the crypt (P < 0.01) relative to non-IRA subjects. Sulindac did not influence the labeling index and the distribution of labeled cells along the crypt. On the contrary, a dramatic decrease in the size and number of polyps was observed after sulindac treatment (P < 0.001). CONCLUSIONS The persistence of a abnormal mucosal proliferation after sulindac therapy, in spite of the reduction of polyp number, suggests caution in assuming a lower risk of rectal cancer in patients with FAP.

Starchy foods and colon proliferation in mice

The effect of starch contained in different foods on colonic proliferation was studied in C57BL/6N mice after four weeks of feeding with 20% fat diets containing cornstarch, white bread, pasta, and rice; an equicaloric amount of sucrose was used in a control diet. Cell proliferation was evaluated in different subsites of the colon (rectal end, mid colon and cecal end) by colchicine arrest and [3H]thymidine incorporation. The following parameters were analyzed: mitotic index (MI), labeling index (LI), and the distribution of labeled cells along the crypt. Different results were obtained in the different subsites. At the rectal end of the colon, all diets containing starch lowered cell proliferation compared with the sucrose diet. The values for MI in the different diets were 2.56 +/- 0.22, 1.73 +/- 0.30, 1.37 +/- 0.19, 1.61 +/- 0.29, and 1.29 +/- 0.31 for control, cornstarch, white bread, pasta, and rice, respectively. Values are means +/- SE (n = 10). The values for LI showed a similar pattern. In the mid colon, the MI was significantly lowered only by the diet containing rice, whereas the DNA synthetic activity (LI) was lowered by cornstarch, pasta, and rice. Toward the cecal end, we observed a significant reduction in MI with diets containing pasta and rice and in the LI with diets containing pasta. The distribution of the LI along the crypt in the different subsites was not significantly affected by experimental dietary variations. The results suggest that starch from different dietary sources might reduce colon proliferation in the mouse.

Mucosal cell proliferation of the rectal stump in ulcerative colitis patients after ileorectal anastomosis

The proliferative activity and polyamine levels of the rectal epithelium in unoperated ulcerative colitis patients and in ulcerative colitis patients after total colectomy and ileorectal anastomosis were determined and compared with control subjects. Cell proliferation was evaluated in rectal biopsies byin vitro3H thymidine incorporation by measuring the labeling index and the position of labeled cells along the crypt; polyamines were determined with a chromatographic method. In ulcerative colitis patients the labeling index was significantly increased, and labeled cells were shifted toward the upper part of the crypt when compared with controls. Ileorectal anastomosis patients showed a normalization of the labeling index and a distribution of labeled cells similar to controls. Polyamine levels were also increased in ulcerative colitis patients; in ileorectal anastomosis patients, the level of polyamines was decreased in respect to unoperated patients and return to normal values except for spermine. Because the increased proliferation and higher polyamine levels are related to increased colon cancer risk, our results confirm that ulcerative colitis is a risk factor for the development of carcinoma. Ileorectal anastomosis may reduce this risk through a normalization of mucosal cell proliferative activity and of some polyamine levels.

Mitotic activity in colorectal mucosa of healthy subjects in two Italian areas with different dietary habits

The proliferative activity was evaluated in colorectal biopsies of 39 healthy subjects living in two distinct geographical areas, Trieste in northern and Florence in central Italy. Subjects living in Trieste had a significantly higher mitotic activity compared with subjects living in Florence (mitoses/cells counted x 100 were 0.17 +/- 0.04 in Trieste and 0.089 +/- 0.02 in Florence). The results of a dietary questionnaire also showed that subjects in Trieste consumed significantly fewer starches, fibers, nitrites, and proteins. However, no correlation was evident between the consumption of these nutrients and intestinal proliferation.

The growth of preneoplastic lesions by 1,2-dimethylhydrazine in rat colon is inhibited by dietary starch.

The effect of dietary starch and sucrose on colon proliferation and the growth of foci of dysplastic crypts in the colon (FDC) were studied in female Sprague-Dawley rats, treated p.o. with 1,2-dimethylhydrazine (DMH). The animals were fed for 30 and 105 days with high fat (23% w/w corn oil) diets in which carbohydrates were represented by corn starch (starch diet) or sucrose (sucrose diet) (46% w/w). After 105 days of feeding, proliferation was markedly reduced in animals fed the starch diet. The number of FDC was not significantly affected by dietary treatments. However, after 30 and 105 days the percent of small FDC (formed by one-two dysplastic crypts) was higher in the animals fed the starch diet when compared to the sucrose diet. In the cecum of the animals fed the starch diet the percent of butyrate, propionic, isovaleric, and valeric over total short-chain fatty acids (SCFA) was increased, whereas the percent of acetic acid was decreased. Cecal pH was also decreased in the animals fed starch. The results suggest that starch diets have a protective role against DMH-colon carcinogenesis in the rat, mediated by a drop in cecal pH and an increased concentration of some SCFA.