DNA adducts in normal colonic mucosa from healthy controls and patients with colon polyps and colorectal carcinomas.

Colon cancer is a multistage process where adenomatous polyps developing in a normal mucosa may further progress to neoplasia. DNA adducts are biomarkers linked to exposure to carcinogenic compounds, tumour formation and clinically observed cancer. Such DNA adducts have been detected in the mucosa of colon cancer patients. The aim of this study was to investigate whether there are differences in DNA adduct levels and patterns in mucosa from patients with colon cancer, polyps and non-cancerous controls and whether some DNA adducts could be markers for colon cancer development. Human colonic biopsies were collected from healthy controls (n = 10), polyp patients (n = 22) (from both normal and polyp tissue) and colon cancer patients (n = 32) (from both tumour tissue and adjacent normal mucosa). In 150 tissues specimens (when small amount of tissue, the same type of tissues were pooled from each patient), DNA adduct levels and patterns were analysed by the (32)P-high-performance liquid chromatography method. There were no significant difference in the total levels of DNA adducts between any of the groups. Levels of two single DNA adducts were decreased in mucosa adjacent to tumours as compared to mucosa from healthy controls. One DNA adduct was found only in tumour tissue and adjacent mucosa from the colon cancer patients. A food derived, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-related DNA adduct was detected in 106 of the 150 tissues analysed, but in similar levels in tissues from controls, polyp patients or cancer patients. In conclusion, three individual DNA adducts may be interesting candidates for further evaluation of their possible role as biomarkers in human carcinogenesis. Furthermore, a food-derived PhIP-related adduct contributes to the general DNA adduct pattern in most individuals, indicating a minor role of this adduct in human colon carcinogenesis.

Gallbladder bile composition in patients with Crohn 's disease.

AIM: To further elucidate the pathogenesis and mechanisms of the high risk of gallstone formation in Crohn's disease. METHODS: Gallbladder bile was obtained from patients with Crohn's disease who were admitted for elective surgery (17 with ileal/ileocolonic disease and 7 with Crohn's colitis). Fourteen gallstone patients served as controls. Duodenal bile was obtained from ten healthy subjects before and after the treatment with ursodeoxycholic acid. Bile was analyzed for biliary lipids, bile acids, bilirubin, crystals, and crystal detection time (CDT). Cholesterol saturation index was calculated. RESULTS: The biliary concentration of bilirubin was about 50% higher in patients with Crohn's disease than in patients with cholesterol gallstones. Ten of the patients with Crohn's disease involving ileum and three of those with Crohn's colitis had cholesterol saturated bile. Four patients with ileal disease and one of those with colonic disease displayed cholesterol crystals in their bile. About 1/3 of the patients with Crohn's disease had a short CDT. Treatment of healthy subjects with ursodeoxycholic acid did not increase the concentration of bilirubin in duodenal bile. Several patients with Crohn's disease, with or without ileal resection/disease had gallbladder bile supersaturated with cholesterol and short CDT and contained cholesterol crystals. The biliary concentration of bilirubin was also increased in patients with Crohn's colitis probably not due to bile acid malabsorption. CONCLUSION: Several factors may be of importance for the high risk of developing gallstones of both cholesterol and pigment types in patients with Crohn's disease.

Ileal pouch-anal anastomosis (IPAA): functional outcome after postoperative pelvic sepsis. A prospective study of 100 patients.

INTRODUCTION: The ileal pouch-anal anastomosis (IPAA) has become a standard procedure for patients with ulcerative colitis requiring surgical intervention. The technique has greatly improved and, since 1990, all patients at Huddinge University Hospital have been operated on with the double stapled technique. Pelvic sepsis is one of the most serious complications postoperatively, and, according to previous reports, leads to impaired function of the pouch and, in some cases, extirpation of the pouch. AIM: The purpose of this study was to find out if pelvic sepsis postoperatively after IPAA leads to impaired functional outcome at long-term follow-up. PATIENTS AND METHODS: One hundred consecutive patients with ulcerative colitis operated on between 1990 and 1997 with double stapled J-shaped pouches were followed prospectively with a standardised questionnaire, clinical follow-up and endoscopy of the pouch. The function of the pouch has been evaluated at a minimum of 2 years after surgery to compare the functional outcome between patients with and without pelvic sepsis postoperatively. RESULTS: Twelve patients developed pelvic sepsis postoperatively. No significant differences were found in pouch evacuation frequency, incontinence, deferral time, usage of protecting pads, skin irritation, evacuation problems, diet, usage of medication or social handicap. There was one failure in the control group. CONCLUSION: In this study, no evidence was found that suggested pelvic sepsis postoperatively impairs functional outcome after IPAA at long-term follow-up.

Outcome of colectomy for slow-transit constipation in relation to presence of small-bowel dysmotility.

PURPOSE: A significant proportion of patients with slow-transit constipation have abnormal small-bowel motility. It is unclear whether abnormal small-bowel motility indicates worse results after surgery for slow-transit constipation. We studied the results of colectomy with ileorectal anastomosis in patients with normal and abnormal antroduodenal manometry findings. METHODS: Seventeen, consecutive patients who had been referred for intractable constipation and who were found to suffer from slow-transit constipation underwent subtotal colectomy. All patients underwent a set of diagnostic investigations, including whole gut transit time, anorectal manometry, antroduodenal manometry, electromyography of the anal sphincter, balloon expulsion test, and defecography. Patients were followed up after five years. RESULTS: Patients' median age at the time of the operation was 46 (range, 23-70) years, and the median duration of constipation was 31 (range, 11-65) years. One patient died 21 days after the operation. Three patients developed intestinal pseudo-obstruction after the operation, and two of these died during the follow-up period. Fourteen patients were available for follow-up after a median of five (range, 4-7) years. Bowel frequency was significantly increased from a median of 0 (range, 0-2) times per week to a median of 30 (range, 10-102) times per week after surgery (P<0.001). The incidence of abdominal pain decreased from 94 to 43 percent. Seven of 13 patients (54 percent) continued to have bloating. At long-term follow-up, 12 of 14 patients (86 percent) reported that they had an overall improvement after surgery, despite continuing pain and bloating in a significant proportion of them. The outcome of surgery was good or excellent in seven of seven patients with normal findings on antroduodenal manometry, but only five of nine patients with abnormal manometry findings attained a good result after surgery. We found a trend (P=0.09) toward better long-term results after surgery for slow-transit constipation in patients with a normal antroduodenal manometry before the operation.

Pouchitis.

PURPOSE OF REVIEW: Total proctocolectomy with ileal pouch-anal anastomosis has become the preferred surgical procedure for ulcerative colitis. Although most patients report a good functional outcome and significant improvement in their quality of life after ileal pouch-anal anastomosis, pouchitis remains the most common long-term complication. This review highlights significant reports on the diagnosis, treatment, and complications of pouchitis in former ulcerative colitis. RECENT FINDINGS: The diagnosis of pouchitis is based on clinical symptoms including increased stool frequency, urgency, rectal bleeding, abdominal cramping, or pelvic discomfort and should be verified by typical findings at endoscopy. Antibiotics such as metronidazole and ciprofloxacin are effective treatments for acute attacks of pouchitis, and for those patients with recurrent or chronic refractory pouchitis, prophylactic therapy with long-term use of the VSL#3 combination of probiotics has now been proved to be highly effective in controlled trials. Most patients with an ileal pouch-anal anastomosis experience a good quality of life, and the risk for removal of the pelvic pouch because of intractable pouchitis is low. Previous reports of neoplastic transformation in certain subgroups of pouch patients have not been substantiated. SUMMARY: Pouchitis is in important clinical entity among ulcerative colitis patients having undergone ileal pouch-anal anastomosis. Diagnosis has become more straightforward, and treatment modalities encompass a variety of remedies, including probiotics. The long-term prognosis is good, and the risk of malignant transformation appears to be very low.