The relationship between faecal bile acid profile with or without supplementation with calcium and antioxidants on recurrence and growth of colorectal polyps.

Faecal bile acids (FBA) have been implicated in colon carcinogenesis. The results of case-control studies of colorectal cancer and polyp patients are, however, conflicting. The aim of this study was to examine the influence of faecal bile acids on occurrence, growth and recurrence of colorectal polyps, and to see if a mixture of calcium and antioxidants might possibly act on cancer precursors through the effect on FBA. A total of 116 polyp-bearing patients were recruited from the outpatients department. Polyps < 10 mm in diameter were left in situ and measured by annual colonoscopy for 3 years. The patients received placebo or a mixture of antioxidants and calcium carbonate, 1.6 g calcium ion daily. Faecal samples were collected annually; the first, 1 month after start of intervention, freeze dried and subjected to bile acid profile analysis. Two age and sex matched control groups were recruited (n = 35), one from healthy volunteers (healthy controls) and one from the outpatients referred for colonoscopy, with no polyps (hospital controls). Twelve of 47 patients from the healthy volunteers had polyps (healthy polyp patients). One or more adenomas were found in 93 patients. The faeces of the hospital controls had significantly higher concentrations of total and secondary bile acids than did the healthy controls. There was no difference in FBA profile between the polyp group and the hospital controls, but significantly higher concentration of total and secondary faecal bile acids in the healthy polyp patients compared with the healthy control group (P < 0.05). No increased concentration of FBA were found in the polyp patients with multiple polyps (n = 21) or previous treatment for colorectal cancer (n = 7). No associations between FBA profile and growth or recurrence of colorectal polyps were found. The polyp patients receiving active medication had higher faecal concentrations of total and secondary bile acids in the beginning of the study than at the end, in spite of a good compliance. The present study does not support bile acids as being important markers of initiation or growth of small and medium sized colorectal adenomas. In the present study the calcium and antioxidants did not seem to affect the growth or recurrence of colorectal adenomas by increased TBA excretion in the faeces.

Growth of colorectal polyps: design of a prospective, randomized, placebo-controlled intervention study in patients with colorectal polyps.

One hundred and sixteen patients were included, during 18 months, in a double-blind placebo-controlled intervention study, with calcium, vitamins A, C, E and selenium (in a cocktail) or placebo against growth of colonic polyps. Patients were randomized within three arms, according to diameter of the largest polyp, < 5 mm, 5-9 mm or > 9 mm. Polyps > 9 mm were resected, the others were left to be measured annually before resection after 3 years. The protocol (performed in all of the patients) included registration of demographic data, family and personal history, measurement of polyps, collection of blood specimens, stools and biopsy samples. Registration of nutritional status, diet history and 5-day prospective food consumption, was performed in 108 patients. The patient compliance was registered every third month by the hospital pharmacist, with concomitant delivery of new boxes of capsules. Additionally, stool collections were performed from all of the patients for the measurement of faecal calcium, bile salts and fat. Inclusion rate of 37, 41 and 38 patients in each of the three 6-month periods was uniform. The group with the largest polyps measuring 5-9 mm comprised 44% of the material. The sex ratio corresponded to that in overall referrals for colonoscopy. The age relationship of size and multiplicity of polyps and the distribution of polyps in the large bowel corresponded to previous experience in polyp-bearing individuals of the same age.(ABSTRACT TRUNCATED AT 250 WORDS)

NSAID-associated gastroduodenal damage: does famotidine protection extend into the mid- and distal duodenum?

Eighteen healthy volunteers were included in a cross-over, double-blind study where 500 mg naproxen b.d. was given for 1 week with 20 mg famotidine b.d., 40 mg nocte or placebo. Endoscopic evaluation of the gastroduodenal mucosa was performed before and after each treatment period, with separate evaluation of the mid- and distal duodenum. 51Cr-EDTA-permeability tests were done to study effects on the mid- and distal gut, and, in addition, symptom registration was performed. The mucosal damage was significant in all treatment periods, and a statistically significant reduction was seen with 20 mg famotidine b.d. for erosive lesions in the stomach/duodenal bulb region as well as for the sum of damage score in the mid- and distal duodenum. The reduction was considerable in a few subjects with extensive duodenal damage. The reduction was considerable in a few subjects with extensive duodenal damage. Intestinal permeation increased significantly in all periods, and was not reduced by famotidine. Symptoms were modest and equal in all periods.

Sucralfate for prevention of naproxen-induced mucosal lesions in the proximal and distal gastrointestinal tract.

To study the protective effect of Sucralfate on Naproxen-induced mucosal lesions, 16 healthy, male volunteers were given Naproxen 500 mg b.i.d. together with Sucralfate 2 g b.i.d. or placebo in a double-blind, crossover study. Drug periods were 1 week, with a 3-week wash out in between. Mucosal lesions in stomach and duodenum were assessed by upper endoscopy before and after each drug period, using a visual analogue with separate scoring of mid- and distal duodenal lesions. 51Cr-EDTA absorption tests were performed to demonstrate possible changes in distal gut permeability. In addition, subjective symptoms were registered. Both drug periods induced significant lesions in the stomach and duodenum. Statistically speaking, fewer changes were found in the stomach and duodenal bulb after Sucralfate co-administration, whereas no significant reduction of lesions was seen in the distal duodenum. The 51Cr-EDTA absorption was increased in both periods, indicating deleterious effects to distal parts of the gut, but our results did not demonstrate Sucralfate-mediated protection from these changes. Symptoms were modest, and equal in the two periods. We conclude that Sucralfate may offer protection in the gastric and proximal duodenal mucosa, but no such protective effect was seen distally to the duodenal bulb.