Pouchitis in ulcerative colitis: correlation between predictors from colectomy specimens and clinico-histological features.

Pouchitis after restorative proctocolectomy for ulcerative colitis is usually of ill-defined etiology and is encountered with sclerosing cholangitis, bacterial overgrowth, and ischemia. Recently, appendiceal involvement, ileitis, and fissures in the colectomy specimen have been associated with short- and long-term development of pouchitis. To corroborate these recent findings, the histology of 40 colectomies (70% males; mean age 46.3 years, age range 20-70 years; mean follow-up period 3.7 years, range 1-13 years) with yearly follow-up biopsies was correlated with pouchitis and clinical symptoms. Appendicitis, fissures, and ileitis were present in 47, 45 and 5% of the patients, respectively. Pouchitis in patients with appendicitis or with fissures was noted in 44 and 50% at first biopsy and in 70 and 58% during follow-up (p = NS). Of the patients without appendicitis or without fissures, 33 and 33% demonstrated pouchitis at the first biopsy and 30 and 55% during follow-up (p = NS). Clinico-histological correlation revealed normal/near-normal biopsies with the lowest clinical severity score in 77% and with the highest clinical score in 43% (p < 0.025). The histological findings of appendiceal involvement, fissuring ulcers, and ileitis in colectomies for ulcerative colitis do not correlate with the finding of pouchitis in early or late pouch biopsies. A high clinical suspicion score is frequently not correlated with significant inflammation of the pouch.

Inflammatory bowel disease is not associated with an increased risk of lymphoma.

BACKGROUND & AIMS: Previous studies of the risk of lymphoma in inflammatory bowel disease patients have provided conflicting results. This study examines the risk of Hodgkin's and non-Hodgkin's lymphoma among patients with inflammatory bowel disease. METHODS: The authors performed a retrospective cohort study using the General Practice Research Database. Inflammatory bowel disease patients were matched to randomly selected controls on age, sex, and primary care practice. Lymphoma rates were also compared with published age- and sex-specific rates. RESULTS: The study included 6605 patients with Crohn's disease, 10,391 with ulcerative colitis, and 60,506 controls followed for an average of 3.7, 3.9, and 4.4 years, respectively. The incidence of lymphoma was not increased in patients with inflammatory bowel disease (relative risk = 1.20; 95% CI, 0.67-2.06). In subgroup analyses, an increased risk was not observed among patients with Crohn's disease (relative risk = 1.39; 95% CI, 0.50-3.40) or ulcerative colitis (relative risk = 1.11; 95% CI, 0.51-2.19). Compared with inflammatory bowel disease patients not treated with azathioprine or 6-MP, the relative risk of lymphoma among the 1465 inflammatory bowel disease patients treated with these medications (average, 106 mg/day for 2.0 years) was 1.27 (95% CI 0.03-8.20). CONCLUSIONS: Patients with inflammatory bowel disease do not have an increased risk of lymphoma as compared with the general population. Although we cannot completely rule out a modest increased risk of lymphoma with azathioprine or 6-MP therapy, an increased risk was not observed in this cohort.

An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis.

OBJECTIVES: Previous research has demonstrated that ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARs) reduce inflammation in two different murine models of colitis. This study was designed to examine the potential efficacy of rosiglitazone, a ligand for the gamma subtype of PPARs, as a therapy for active ulcerative colitis. METHODS: Fifteen patients with mild to moderately active ulcerative colitis despite therapy with 5-aminosalicylic acid compounds were enrolled in an open-label study of rosiglitazone (4 mg b.i.d. p.o.) for 12 wk. Thirteen of 15 patients were receiving concomitant therapy with corticosteroids and/or immunomodulator medications. Disease activity was measured with the Disease Activity Index. RESULTS: After 12 wk of therapy, four patients (27%) had achieved clinical remission, of whom three (20%) also had an endoscopic remission. Four additional patients (27%) had a clinical response without achieving remission. Two patients were hospitalized with worsened disease activity, and one patient was withdrawn for nephrotic syndrome. CONCLUSIONS: These data suggest that ligands for the gamma subtype of PPARs may represent a novel therapy for ulcerative colitis. A double blind, placebo-controlled, randomized trial is warranted.

Distinction between dysplasia-associated lesion or mass (DALM) and adenoma in patients with ulcerative colitis.

Polyps with epithelial dysplasia in ulcerative colitis (UC) represent either dysplasia-associated lesions or masses (DALMs) or sporadic adenomas. DALMs are frequently associated with associated carcinoma and are an indication for colectomy. Removal of the polyp is treatment of choice for sporadic adenomas. Differentiating between these 2 lesions is not always easy. The goal of this study was to distinguish DALMs from adenomas in patients with UC on a genetic basis. We evaluated genetic alterations in DALMs and compared them with a previously published set of dysplastic polyps in patients with UC that were considered adenomas for the following reasons: (1) polyps were located outside of current active disease; (2) polyps had histological features of sporadic adenomas; and (3) patients displayed a uneventful follow-up after polypectomy (UC-adenomas). In addition, adenomas not associated with UC were studied. Genetic alterations on chromosome 3p were assessed for the markers D3S1766, D3S2409, and D3S2387. LOH with or without microsatellite instability was found in 70%, 37%, and 57% of cases of DALM, respectively. In contrast, UC-adenomas lesions exhibited genetic alterations in 8.3%, 11.7%, and 15.3% for the respective markers. Spontaneous adenomas exhibited genetic alterations in 10.5%, 7.1%, and 0% of cases, which were not significantly different from the UC-adenoma results. These results indicate that UC-adenomas are genetically and biologically similar to sporadic adenomas and that UC-adenomas may biologically represent sporadic adenomas, supporting on a genetic basis the criteria chosen to diagnose adenomas in UC. Genetic markers on chromosome 3p may be useful in the differential diagnosis between DALM and UC-adenomas.

Cancer risk in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk for developing cancer of the gastrointestinal tract, particularly colorectal cancer. Because of the relative rarity of IBD in the general population, it has been difficult to quantify this risk. Efforts to reduce the risk have included both prophylactic surgery and endoscopic screening programs. Because of the potential impact on quality of life and life expectancy, the optimal strategy for reducing this risk has not been defined. This article reviews the current literature relating to the risk of cancer for patients with IBD and methods to reduce this risk.

Mucinous cystadenoma: pitfalls of differential diagnosis.

Cystic neoplasms of the pancreas often are difficult to differentiate from pseudocysts. It has been proposed that a history of clinical pancreatitis, elevated serum pancreatic enzymes, elevated cyst fluid amylase, and a communication with the pancreatic duct suggest the diagnosis of a pseudocyst. We report the case of a young woman who presented with a cystic mass in the pancreas and was thought to have a pseudocyst because of the above; at surgery, a mucinous cystadenoma was documented. The pitfalls of differentiating neoplastic cysts of the pancreas from pseudocysts are discussed.

Limited weight losses with a gastric balloon.

An evaluation of the Garren-Edwards gastric bubble in the treatment of obesity was done. Several clinical trials have compared the effects of behavior therapy with and without the bubble, but the effects of the bubble alone have not been previously evaluated. Ten obese women averaging 91% overweight received the bubble without adjunctive therapy during a 12-week treatment period. Frequent psychological and laboratory measures as well as weight were obtained during the study to explore the possible mechanisms of the bubble's effect and its side effects. Mean weight change was -2.5 kg, with a range of -8.8 to +1.6 kg. Four patients lost more than 3.5 kg, three lost less than 3.5 kg, and three gained weight. The Garren-Edwards gastric bubble alone does not appear to provide significant benefit to most obese patients.

Direct and indirect effects of dextrose and amino acids on gut mass.

Oral intake of an elemental diet maintains small intestinal mucosal mass compared to the atrophy seen after intravenous infusion of the same diet. The greatest difference in intestinal mass occurs in the proximal bowel and is thought to occur because of rapid absorption in the proximal small bowel. This study was designed to determine the effects of the individual components of the elemental diet and their site of administration within the small bowel on small intestinal mass. Rats were maintained on intravenous alimentation and the proximal gut (by intragastric infusion) or the ileum was continuously infused with equal volumes of 30% dextrose, 5% dextrose, 5% amino acids, saline, or 30% mannitol. After 1 week of combined intravenous alimentation and gut infusion, the rats were killed and parameters of small intestinal epithelial mass were determined sequentially for the entire bowel. Although saline- and mannitol-infused controls did not differ from uninfused intravenously fed rats, proximal infusion of 30% dextrose reproduced the effects of a complete elemental diet. Proximal infusion of amino acids but not 5% dextrose had a limited effect on the duodenum and jejunum. Ileal infusion of 30% dextrose led to local hyperplasia of the site of infusion and in addition produced hyperplasia of the proximal gut. Ileal amino acid infusion, but not 5% dextrose infusion, led to local ileal hyperplasia. We conclude that: (1) intraluminal dextrose and amino acids have direct effects in maintaining gut mass (2) the gut is more responsive to amino acids compared to 5% dextrose, and (3) ileal 30% dextrose infusion leads to remote effects in the proximal gut, perhaps mediated by hormonal or neurovascular factors.

Small-bowel resection. Oral intake is the stimulus for hyperplasia.

Small-bowel resection leads to hyperplasia of the residual small intestine, However, the factors initiating small-bowel hyperplasia are not clearly understood, although oral intake either by direct contact with the small bowel or via hormonal or neurovascular factors has been suggested as the major stimulus. In order to determine whether oral intake is an obligatory prerequisite for small-intestinal hyperplasia, we compared rats one week after undergoing a 70-cm proximal intestinal resection with sham-operated animals. Resected, orally fed rats demonstrated small-intestinal hyperplasia, whereas resected and sham-operated intravenously alimented rats did not. There were no differences in gut weight, mucosal weight, mucosal protein, or DNA between resected or sham-operated intravenously alimented rats. These data provide direct experimental proof that oral intake is a necessary stimulus for small-intestinal hyperplasia after resection.