Collagenous pouchitis.

Collagenous colitis is characterised by watery diarrhoea, normal colonic mucosa on endoscopy, diffuse colitis with surface epithelial injury, and a distinctive thickening of the subepithelial collagen table on histology. Some patients can develop medically refractory collagenous colitis, in which case they may require surgical intervention. This is the first report of collagenous pouchitis in a collagenous colitis patient with proctocolectomy and ileal pouch-anal anastomosis. A patient with medically refractory collagenous colitis who underwent a total proctocolectomy and ileal pouch-anal anastomosis was sequentially evaluated with an endoscopy and histology of the colon, distal small intestine, and ileal pouch. A 58-year-old female had a 10-year history of collagenous colitis before having a total proctocolectomy and ileal pouch-anal anastomosis for medically refractory disease. The histologic features of collagenous colitis were present in all colon and rectum biopsy or resection specimens, but were absent in the distal ileum specimen. The post-operative course was complicated by persistent increase of stool frequency, abdominal cramps, and incontinence. A pouch endoscopy was performed 3 years after ileal pouch-anal anastomosis which showed the histologic features of collagenous colitis in the ileal pouch, collagenous pouchitis, while the pre-pouch neo-terminal ileum had no pathologic changes. After antibiotic therapy, the histologic changes of collagenous pouchitis resolved. This is the first reported case of collagenous pouchitis. Since the abnormal collagen table and its associated features were only present in the pouch and absent in the neo-terminal ileum, and the patient had histologic improvement after antibiotic therapy, it would suggest that faecal stasis and bacterial load may play a role in the pathogenesis.

Urinary excretion of N1-acetylspermidine and other acetylated and free polyamines in the 1,2-dimethylhydrazine model of experimental rat colon cancer.

1,2-Dimethylhydrazine (DMH) is a potent procarcinogen with selectivity for the colon. Recently, it has been demonstrated that levels of N1-acetylspermidine were elevated 2-3-fold in colonic tumors induced by this agent compared to control tissues. To determine whether alterations in the urinary levels of this acetylated polyamine or other polyamines were useful biochemical markers for colon cancer in this experimental model, rats were given s.c. injections of DMH (20 mg/kg body weight/week) or diluent for 26 weeks. One week after the last injection, control and DMH-treated animals were placed in separate metabolic cages and their urine was collected for 24 h. The urinary levels (expressed as nmol/mg creatinine) of putrescine, spermidine, spermine, N1-acetylspermidine, and N8-acetylspermidine were then analyzed by high-performance liquid chromatography. Animals from each group were then sacrificed and their colons were examined for tumors. The results of these studies demonstrated that the urinary level of N1-acetylspermidine was an excellent biochemical marker for colonic tumors induced by DMH. At 18.3 nmol/mg creatinine, N1-acetylspermidine was 100% sensitive and specific for colon cancer. Moreover, urinary levels of N1-acetylspermidine were better for this purpose than the N1-acetylspermidine/N8-acetylspermidine molar ratio, a marker previously suggested to be more specific for certain cancers than free polyamines.

The impact of ursodeoxycholic acid on cancer, dysplasia and mortality in ulcerative colitis patients with primary sclerosing cholangitis.

BACKGROUND: Colorectal cancer in primary sclerosing cholangitis patients with ulcerative colitis is mostly right-sided where concentrations of carcinogenic secondary bile acids are highest. AIM: To investigate whether ursodeoxycholic acid could be chemopreventive for colorectal cancer. METHODS: A historical cohort study was performed on primary sclerosing cholangitis patients with ulcerative colitis where the 28 patients (cases) who were treated with ursodeoxycholic acid for at least 6 months (mean 3.4 +/- 2.7 years) were compared with the 92 patients (controls) who were not treated with ursodeoxycholic acid. The primary outcomes were colorectal cancer and dysplasia. The secondary outcome was overall mortality. RESULTS: The cumulative incidence of dysplasia or cancer was not significantly different between cases and controls (P = 0.17 by log-rank test). The adjusted relative risk for cases of developing dysplasia or cancer was 0.59 (95% CI 0.26-1.36). The cumulative mortality was significantly different between groups (P = 0.02 by log-rank test). The adjusted relative risk for cases of death was 0.44 (95% CI 0.22-0.90). CONCLUSION: In ulcerative colitis patients with primary sclerosing cholangitis, ursodeoxycholic acid did not reduce the risk of developing cancer or dysplasia. However, ursodeoxycholic acid may reduce mortality.

Maintenance therapy with a probiotic in antibiotic-dependent pouchitis: experience in clinical practice.

BACKGROUND: Management of antibiotic-dependent pouchitis is often challenging. Oral bacteriotherapy with probiotics (such as VSL #3) as maintenance treatment has been shown to be effective in relapsing pouchitis in European trials. However, this agent has not been studied in the US, and its applicability in routine clinical practice has not been evaluated. AIM: To determine compliance and efficacy of probiotic treatment in patients with antibiotic-dependent pouchitis. METHODS: Thirty-one patients with antibiotic-dependent pouchitis were studied. VSL #3 is a patented probiotic preparation of live freeze-dried bacteria. All patients received 2 weeks of ciprofloxacin 500 mg b.d. followed by VSL #3 6 g/day for 8 months. Baseline Pouchitis Disease Activity Index scores were calculated. Patients' symptoms were reassessed at week 3 when VSL #3 therapy was initiated and at the end of the 8-month trial. Some patients underwent repeat pouch endoscopy at the end of the trial. RESULTS: All 31 patients responded to the 2-week ciprofloxacin trial with resolution of symptoms and they were subsequently treated with VSL #3. The mean duration of follow-up was 14.5+/-5.3 months (range: 8-26 months). At the 8-month follow-up, six patients were still on VSL #3 therapy, and the remaining 25 patients had discontinued the therapy due to either recurrence of symptoms while on treatment or development of adverse effects. All six patients who completed the 8-month course with a mean treatment period of 14.3+/-7.2 months (range: 8-26 months) had repeat clinical and endoscopic evaluation as out-patients. At the end of 8 months, these six patients had a mean Pouchitis Disease Activity Index symptom score of 0.33+/-0.52 and a mean Pouchitis Disease Activity Index endoscopy score of 1.83+/-1.72, which was not statistically different from the baseline Pouchitis Disease Activity Index endoscopy score of 2.83+/-1.17 (P=0.27). CONCLUSION: This study was conducted to evaluate bacteriotherapy in routine care. The use of probiotics has been adopted as part of our routine clinical practice with only anecdotal evidence of efficacy. Our review of patient outcome from the treatment placebo showed that only a minority of patients with antibiotic-dependent pouchitis remained on the probiotic therapy and in symptomatic remission after 8 months.

Chronic hepatitis: disease factors at diagnosis predictive of mortality.

PURPOSE: Chronic hepatitis is known to be a disease with substantial mortality. The purpose of this study was to identify prognostic factors in a large group of patients with chronic hepatitis. We also wanted to determine whether the aminopyrine breath test (ABT) is of additional prognostic value in evaluation of this disease. PATIENTS AND METHODS: We studied 94 patients who had had a biopsy-proven diagnosis and an ABT between June 1, 1977, and June 30, 1981. Clinical features and biochemical test results at the time of diagnosis were retrieved from medical records, and histologic severity was assessed by reviewing all liver biopsy specimens under code. Survival was determined at a mean of 60 months. Data were studied with a Cox proportional hazards model to identify predictors of mortality and to control for confounding variables. RESULTS: Cumulative mortality as of December 31, 1985, was 5 percent in chronic persistent hepatitis, 6 percent in chronic active hepatitis, 29 percent in chronic active hepatitis with bridging necrosis, and 53 percent in chronic active hepatitis with cirrhosis. Histologic severity was a predictor of death (p less than 0.005). Other predictors of mortality were disease caused by hepatitis B virus (p less than 0.005), a high alkaline phosphatase level (p less than 0.025), a low alanine aminotransaminase level (p less than 0.001), and a depressed ABT result (p less than 0.005). CONCLUSION: The results suggest that patients with chronic hepatitis with one or more of these risk factors have an increased mortality and should be followed closely for liver failure, which may necessitate medical therapy or surgical intervention.

Intestinal adenocarcinoma in Crohn's disease: a report of 30 cases with a focus on coexisting dysplasia.

There are relatively few reports that detail the types of intestinal adenocarcinoma complicating Crohn's disease and examine associated epithelial dysplasia. We determined the prevalence, grade, and type of dysplasia found adjacent to and distant from Crohn's-related adenocarcinomas. Thirty cases of resected Crohn's-related adenocarcinoma were reviewed, and histologic type, degree of differentiation, TNM stage, and the presence or absence, grade, and location of dysplasia were recorded. Most of the patients were male (70%). The median ages at diagnosis of Crohn's disease and adenocarcinoma were 34 and 49 years, respectively. The extent of Crohn's disease included ileocolitis in 21 patients, only colonic disease in six, and only small bowel disease in three. In most cases (67%), carcinoma was found incidentally at surgery. All carcinomas arose in areas involved by Crohn's disease. Eight (27%) adenocarcinomas arose in the small bowel, and 22 (73%) arose in the colon, including two in out-of-circuit rectums. Most carcinomas (63%) were poorly differentiated. Dysplasia was found adjacent to the carcinoma in 26 (87%) cases. Of the colorectal carcinomas, 19 (86%) had adjacent dysplasia, and nine (41%) had distant dysplasia. In conclusion, most cases of Crohn's-related intestinal adenocarcinoma have dysplasia in adjacent mucosa, and 41% of those arising in the colorectum have distant dysplasia, supporting a dysplasia-carcinoma sequence in Crohn's disease.

A randomized clinical trial of ciprofloxacin and metronidazole to treat acute pouchitis.

Metronidazole is effective for the treatment of acute pouchitis after ileal pouch-anal anastomosis, but it has not been directly compared with other antibiotics. This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis. Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less. Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9). Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy. Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores. Ciprofloxacin lowered the PDAI score from 10.1+/-2.3 to 3.3+/-1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7+/-2.3 to 5.8+/-1.7 (p = 0.0002). There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9+/-1.2 versus 3.8+/-1.7; p = 0.002), symptom score (2.4+/-0.9 versus 1.3+/-0.9; p = 0.03), and endoscopic score (3.6+/-1.3 versus 1.9+/-1.5; p = 0.03). None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy. Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores. Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole. Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis.

Cigarette smoking and ulcerative colitis: a case-control study.

OBJECTIVE: To determine whether the previously reported decreased risk of ulcerative colitis in current smokers and increased risk in former smokers are explained by age, sex, race, ethnicity, or socioeconomic status. DESIGN: We conducted a case-control study at a university hospital gastroenterology clinic. MATERIAL AND METHODS: One hundred patients with ulcerative colitis and 100 age- and sex-matched community control subjects were randomly selected for a telephone interview to collect information on smoking habits, race, religion, income, education, and occupation. Smoking habits at the onset of symptoms were analyzed with use of conditional logistic regression for matched data to obtain adjusted odds ratios and 95% confidence intervals for current or former smokers. RESULTS: In comparison with those who had never smoked, current smokers were less likely to have ulcerative colitis: odds ratio = 0.13; 95% confidence interval = 0.05 to 0.38. Former smokers had no increased risk for ulcerative colitis: odds ratio = 1.24; 95% confidence interval = 0.52 to 2.95. No dose-response effect was noted on the basis of pack-years of cigarette smoking, and among former smokers, the interval since quitting smoking was not significantly associated with the relative risk of ulcerative colitis. No confounding effect was detected from race, religion, income, education, or occupation. CONCLUSION: An association seems to exist between ulcerative colitis and nonsmoking; perhaps patients with ulcerative colitis who smoke are less likely to experience symptoms than are nonsmokers because of the effects of nicotine.

Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis.

Patients with extensive ulcerative colitis have a high risk of developing colon cancer. The etiology of mucosal dysplasia, a premalignant lesion that is used as a screening test in surveillance programs, is unknown. Previously, a case-control study [Lashner et al. (1989) Gastroenterology 97:255-259] suggested that folate supplementation was associated with a 62% reduction in the risk of developing dysplasia or cancer. The current case-control study was performed to obtain a better definition of this risk. All 67 patients with chronic ulcerative pancolitis having surveillance colonoscopy during a 1-year period were entered. There were 6 cases (4 with dysplasia and 2 with cancer) and 61 controls (no cancer or dysplasia). Red blood cell folate, reflecting intermediate-term stores, was a mean of 66.2 ng/ml lower in cases compared to controls. Serum folate, reflecting short-term stores, was not different between groups. Adjusting for confounding effects of age, sex, race, disease duration, and folate supplementation, the risk of dysplasia or cancer was significantly decreased by 18% for each 10 ng/ml increase in red blood cell folate (odds ratio 0.82, 95% confidence interval 0.68-0.99). Vitamins A, D, and E and carotene were lower in cases than in controls, but no water-soluble vitamin other than red blood cell folate was associated with an increased cancer risk. Depressed red blood cell folate is associated with an increased risk of dysplasia and cancer in patients with ulcerative colitis and may be a risk factor for neoplastic transformation.

Cancer biology in ulcerative colitis and potential use in endoscopic surveillance.

Because patients with longstanding ulcerative colitis are at an increased risk for developing colorectal cancer, surveillance colonoscopy and colectomy for dysplasia or asymptomatic cancer is advised as a method of reducing cancer-related mortality. Generally, the use of dysplasia as a criterion for a positive test in cancer surveillance has performed poorly. The emerging field of colon cancer genetics has identified several important tumor markers that have the potential to improve sensitivity for the detection of early neoplasia. Specifically, p53 tumor suppressor gene mutations, aneuploidy, and mucin-associated sialosyl-Tn expression appear most promising for future use in surveillance programs.

Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection.

BACKGROUND: Patients who have undergone ileal resection are at risk for developing magnesium depletion/deficiency because of poor absorption and decreased intake as well as increased endogenous losses. Magnesium repletion is difficult to accomplish because of the cathartic action of most oral magnesium supplements at therapeutic doses. The results of in vitro and in situ studies show that magnesium diglycinate (chelate) represents a highly available form of magnesium that is absorbed in part as an intact dipeptide in the proximal small intestine. METHODS: We conducted a double-blind, randomized crossover trial with 12 patients who had ileal resections in order to compare the bioavailability of a 100-mg dose of 26Mg-labeled chelate with MgO in this patient population. RESULTS: For the patient group as a whole, 26Mg absorption was low but was not different for the two supplements (23.5% vs 22.8% for magnesium chelate and MgO, respectively). However, 26Mg absorption was substantially greater from the chelate (23.5% vs 11.8%; p < .05) in the four patients who showed the greatest impairment of magnesium absorption with MgO and was better tolerated by all patients. Peak isotope enrichment also occurred significantly earlier after 26Mg chelate than after 26MgO ingestion (mean difference 3.2 +/- 1.3 hours; p < .05), and the area under the enrichment vs time curve was greater after chelate ingestion (p < .05). CONCLUSIONS: Data from this study support the suggestion that some portion of magnesium diglycinate is absorbed intact, probably via a dipeptide transport pathway. Magnesium diglycinate may be a good alternative to commonly used magnesium supplements in patients with intestinal resection.

Colorectal cancer in ulcerative colitis patients: survival curves and surveillance.

BACKGROUND: Survival curves can provide useful information for designing cancer surveillance programs. OBJECTIVE: To outline how to derive the density and hazard functions from the survival curve and to use this information to make recommendations regarding cancer surveillance in patients with ulcerative colitis. DISCUSSION: The hazard of cancer or dysplasia remains low during the first decade of ulcerative colitis but rises exponentially thereafter. After 40 years, approximately 20% of patients with ulcerative colitis acquire cancer or dysplasia per year. CONCLUSION: A reasonable recommendation for cancer surveillance based on information from survival curves would be a colonoscopy with biopsy approximately 10 years after the onset of ulcerative colitis, and repeated every 3 years for the next decade, every 2 years for the subsequent decade, and every year thereafter. Prophylactic proctocolectomy is an option after 40 years of disease due to the extremely high cancer risk, but data supporting this option are sparse.

Use of old and new oral 5-aminosalicylic acid formulations in inflammatory bowel disease.

Although sulfasalazine, a 5-aminosalicylic acid (5-ASA) agent, is still the anti-inflammatory agent of choice for ulcerative colitis and Crohn's disease, newer formulations, which release drug to specific regions of the colon for maximal efficacy, also can be appropriate first-line agents. This article reviews recent clinical studies of therapy with older and newer 5-ASA formulations.

Industrial risk factors for colorectal cancer.

Colorectal cancer is the second most common malignancy in the United States, and its incidence rates have sharply increased recently, especially in males. Industrial exposures, both occupational and environmental, are important colorectal cancer risk factors that are generally unrecognized by clinicians. Migration studies have documented that colorectal cancer is strongly associated with environmental risk factors. The causal role of occupational exposures is evidenced by a substantial literature associating specific work practices with increased colorectal cancer risks. Industrially related environmental exposures, including polluted drinking water and ionizing radiation, have also been associated with excess risks. Currently, there is a tendency to attribute colorectal cancer, largely or exclusively, to dietary and other lifestyle factors, thus neglecting these industrially related effects. Concerted efforts are needed to recognize the causal role of industrial risk factors and to encourage government and industry to reduce carcinogenic exposures. Furthermore, cost-effective screening programs for high-risk population groups are critically needed to further reduce deaths from colorectal cancer.

The impact of ulcerative colitis on the long-term outcome of patients with primary sclerosing cholangitis.

BACKGROUND: The impact of ulcerative colitis (UC) on the outcome of primary sclerosing cholangitis (PSC) outcome remains unclear. AIM: To investigate whether the presence of UC is associated with a worse clinical of associated PSC. METHODS: A total of 222 patients with PSC (167 with UC and 55 without UC) seen and followed at a single centre from 1985 to 2011 were included. Clinical and demographic variables were obtained and patients were followed until the date of their last clinic visit. RESULTS: The median age at presentation of PSC with associated UC was 38 vs. 47 years without UC (P < 0.001). At presentation, median serum bilirubin (2.1 vs. 4.5, P < 0.001) and the Mayo PSC Risk Score (0.95 vs. 1.69, P < 0.001) were lower in those with UC vs. those without UC. A total of 55 of 167 (32.9%) patients with PSC-UC developed colon neoplasia in contrast to 1 of the 55 (1.8%) patients with PSC. (P < 0.001) On proportional hazards analysis, UC (hazard ratio (HR) = 0.90 [95% confidence interval (CI): 0.60-1.34, P = 0.60] was not associated with death or orthotopic liver transplantation (OLT), when adjusting for gender, Mayo risk score and year of PSC diagnosis; whereas the revised Mayo risk score [HR = 5.08, 95% CI: (2.62-9.86), P < 0.001] was associated with a greater risk of OLT or death. CONCLUSIONS: Primary sclerosing cholangitis often is recognised at an early stage in patients with concurrent ulcerative colitis; ulcerative colitis has no impact on long-term prognosis in terms of liver-related outcomes when adjusted for the severity of liver disease.

The effects of liver transplantation on the clinical course of colitis in ulcerative colitis patients with primary sclerosing cholangitis.

BACKGROUND: The course of ulcerative colitis (UC) following orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) is unclear. AIM: To investigate the clinical course of UC, before and after OLT for PSC. METHODS: From a historical cohort of 86 patients with PSC-UC who underwent OLT, 77 patients who were followed up at our institution both before and after OLT from 1985 to 2011 were included. RESULTS: Ulcerative colitis was diagnosed in 77 (97.5%) patients before OLT. Nineteen of 77 (24.7%) patients underwent colectomy before OLT. In the other 58 patients, the course of UC after OLT when compared to the last 5 years before OLT was quiescent in 48 patients (82.8%) while 9/58 (15.5%) of patients underwent colectomy post-OLT. There was a total of 97 colitis flares over a total of 621 years of follow-up from PSC/UC diagnosis to OLT (0.156 flares per patient year) whereas post-OLT, there were 31 flares over a total of 511 years of post-OLT follow-up (0.061 flares per patient year) (P < 0.001). On univariable analysis, the number of UC flares [Odds ratio (OR) 1.52; 95% Confidence interval (1.02-2.27), P = 0.04] and dysplasia [OR 47.00; 95% CI (6.48-340.66), P < 0.001] increased the risk of colectomy following OLT; the use of corticosteroids [OR 0.07; 95% CI (0.01-0.63), P = 0.008] and 5-aminosalicylate [OR 0.18; 95% CI (0.04-0.83), P = 0.04] was protective. CONCLUSIONS: Ulcerative colitis in the presence of primary sclerosing cholangitis remains quiescent, and may improve in most patients after orthotopic liver transplantation.