Scintigraphic imaging and absorption of a 5-aminosalicylic acid enema in patients with ileorectal anastomosis.
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Ileorectal anastomosis (IRA) is a possible surgical treatment for hyperacute and drug-unresponsive forms of ulcerative colitis (UC). UC relapses in the rectal remnant usually are prevented by chronic administration of 5-aminosalicylic acid (5-ASA) in topical formulations. The relationships between intestinal absorption and pattern of luminal spread of 5-ASA enemas are still unknown in patients with IRA. We correlated the absorption of a 5-ASA enema with its spread in the distal bowel of patients with IRA as assessed by 99mTc radioenema imaging. METHODS: Eight patients with UC in remission and previous IRA received a therapeutic 50-mL 5-ASA enema labeled with 99mTc-sulfer colloid. Absorbed 5-ASA and its major metabolite, acetyl 5-ASA, were measured in plasma, and dynamic images of radiolabeled enema were obtained for 6 h. The retrograde ileal spread (RIS) was determined and expressed as percentage of total enema radioactivity. Plasma levels of 5-ASA and acetyl 5-ASA were measured in six healthy volunteers after administration of the same enema volume with no radiolabeling. RESULTS: The mean 5-ASA plasma level was 0.70 microg/mL (range 0.37-0.95 microg/mL) in patients and 0.96 microg/mL (range 0.78-1.16 microg/mL) in healthy volunteers (P = not significant), and the mean acetyl 5-ASA plasma levels were 0.89 microg/mL (range 0.44-1.19 microg/mL) and 0.84 microg/mL (range 0.51-1.02 microg/mL), respectively (P = not significant). Radioenema imaging allows RIS assessment of patients with IRA. The mean value was 8.5% (range 2%-19.3%) of administered radioactivity, which correlated significantly with the total absorption of 5-ASA in the IRA group (P = 0.033, linear correlation test). Rectal wall contractions recognized by dynamic radioenema imaging were defined as a common cause of RIS episodes. CONCLUSION: In IRA patients, 5-ASA plasma levels were similar to those in healthy volunteers after administration in enema. Only part of a 50-mL 5-ASA enema reaches the ileum, and radiolabeled imaging shows the degree and number of these RIS episodes. The absorption of 5-ASA can increase in patients compared with healthy volunteers, in the presence of either occasional but significant ileal spread associated with postural factors and abdominal wall contraction or multiple moderate episodes of radioenema backdiffusion related to rectal wall motility. (+info)
Ileoanal anastomosis with reservoirs: complications and long-term results.
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OBJECTIVE: To determine the rate of complications of ileoanal pouch anastomosis, their treatment and their influence on a successful outcome. DESIGN: A computerized database and chart review. SETTING: Three academic tertiary care health centres. PATIENTS: All 239 patients admitted for surgery between 1981 and 1994 with a diagnosis of ulcerative colitis and familial adenomatosis coli. INTERVENTIONS: Sphincter-saving total proctocolectomy and construction of either S-type of J-type ileoanal reservoir. OUTCOME MEASURES: Indications, early and late complications, incidence of pouch excision. RESULTS: Of the 239 patients, 228 (95.4%) were operated on for ulcerative colitis and 11 (4.6%) for familial polyposis coli. One patient in each group was found to have a carcinoma not previously diagnosed. Twenty-eight patients had poor results: in 17 (7.1%) the ileostomy was never closed or was re-established because of pelvic sepsis or complex fistulas, sclerosing cholangitis or severe diarrhea; 11 (4.6%) patients required excision of the pouch because of anal stenosis, perirectal abscess-fistula or rectovaginal fistula. Three patients died--of suicide, and complications of liver transplantation and HIV infection. Thus, 208 patients maintained a functioning pouch. The early complication rate (within 30 days of operation) was 57.7% (138 patients) and the late complication rate was 52.3% (125 patients). Pouchitis alone did not lead to failure or pouch excision. Emptying difficulties in 25 patients with anal stenosis were helped in 2 by resorting to intermittent catheterization. Patients with indeterminate colitis had a higher rate of anorectal septic complications, and all patients having Crohn's disease after pouch construction had complicated courses. CONCLUSIONS: The complication rate associated with ileoanal pouch anastomosis continues to be relatively high despite increasing experience with this technique. Overall, however, a satisfactory outcome was obtained in 87% of patients. (+info)
Pancolonic chromosomal instability precedes dysplasia and cancer in ulcerative colitis.
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Patients with long-standing ulcerative colitis (UC) are at increased risk for colon cancer. These cancers are thought to arise from preexisting dysplasia in a field of abnormal cells that often exhibits aneuploidy and p53 abnormalities. Using dual color fluorescence in situ hybridization with centromere probes and locus-specific arm probes for chromosomes 8, 11, 17, and 18, we demonstrate that chromosomal instability (CIN) is present throughout the colon of UC patients with high-grade dysplasia or cancer. In rectal biopsies that were negative for dysplasia, abnormalities in chromosomal arms, especially losses, were most common, whereas centromere gains were most common in dysplasia and cancer. The frequency and type of abnormalities varied between the chromosomes examined; chromosome 8 was the least affected, and 17p loss was found to be an early and frequent event. Chromosomal arm instability showed 100% sensitivity and specificity for distinguishing control biopsies from histologically negative rectal biopsies from these UC patients, raising the possibility that a screen for CIN might detect the subset of UC patients who are at greatest risk for development of dysplasia and cancer. These results suggest that dysplasia and cancer in UC arise from a process of CIN that affects the entire colon; this may provide the mutator phenotype that predisposes to loss of tumor suppressor genes and evolution of cancer. (+info)
Low molecular weight heparin as adjuvant therapy in active ulcerative colitis.
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BACKGROUND: Heparin given intravenously has shown beneficial effects in the treatment of refractory ulcerative colitis in open trials. Low molecular weight heparin (LMWH) offers advantages in the method of administration but have not been evaluated in inflammatory bowel disease conditions. AIM: To assess the tolerability and safety of subcutaneous self-administered LMWH in outpatients with refractory ulcerative colitis and to evaluate any potential adjuvant therapeutic effect. PATIENTS AND METHODS: Twelve patients with mild to moderately active ulcerative colitis were included in the trial. The patients had either responded poorly to treatment with conventional therapy, including oral and/or rectal glucocorticosteroids, or had experienced a rapid relapse during or shortly after GCS therapy. Dalteparin sodium 5000 units s.c. injection was administered twice daily for 12 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms, and endoscopic and histological scores were analysed. Leucocyte scanning was performed at inclusion and at the end of the study. RESULTS: Tolerability and compliance were excellent and no serious adverse events occurred. Eleven patients improved symptomatically and six (50%) attained complete remission after 12 weeks of treatment. Endoscopic, scintigraphic and histological scores were found to be significantly improved. CONCLUSION: Self-administered LMWH given s.c. may be a safe adjuvant therapy for patients with active, glucocorticosteroids-refractory ulcerative colitis. A controlled trial should be undertaken to confirm the positive effects found in this study. (+info)
Titres of anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease are not related to disease activity.
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In the systemic vasculitides, serial measurement of titres of anti-neutrophil cytoplasmic autoantibodies (ANCA) is useful for follow-up of disease activity and prediction of relapses. ANCA have been detected in patients with inflammatory bowel disease, but their relation to disease activity in these diseases is unclear. We analysed the relation between disease activity and ANCA titres as determined by indirect immunofluorescence in paired samples obtained during active disease and at remission from individual patients with ulcerative colitis (n=60) and Crohn's disease (n=101). In addition, patients were followed prospectively, to study the fluctuations of ANCA with time in relation to disease activity. We did not detect a correlation between disease activity and ANCA titres, either in paired samples from active disease and remission, or in serial samples, either in ulcerative colitis or in Crohn's disease. In contrast to the ANCA-associated systemic vasculitides, serial measurement of ANCA titres is not useful in the monitoring of disease activity in patients with inflammatory bowel disease. (+info)
Expression of lymphocyte-endothelial receptor-ligand pairs, alpha4beta7/MAdCAM-1 and OX40/OX40 ligand in the colon and jejunum of patients with inflammatory bowel disease.
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BACKGROUND: The interaction between leucocytes and vascular endothelial cells is essential for leucocyte migration into inflammatory sites. AIMS: To study the local expression of the pairs of complementary molecules, alpha4beta7/mucosal addressin cell adhesion molecule (MAdCAM-1) and OX40/OX40 ligand in the lamina propria of the colon and jejunum of patients with inflammatory bowel disease. METHODS: Ten patients with active ulcerative colitis (UC), nine with active Crohn's disease (CD), and seven irritable bowel syndrome (IBS) controls were submitted to endoscopic and peroral jejunal biopsies. Specimens were immunostained by indirect alkaline phosphatase using antibodies against CD3, intercellular adhesion molecule (ICAM) 1, alpha4beta7, MAdCAM-1, and OX40. An OX40-mouse-IgG fusion protein was used to detect OX40 ligand on frozen sections. Immunohistological analysis was carried out by optical microscopy using a computer assisted image analyser. RESULTS: Colonic lamina propria of patients with CD and UC showed increased density of CD3+, alpha4beta7+, and OX40+ cells compared with IBS controls. ICAM-1, MAdCAM-1, and OX40 ligand positive vessels were also increased compared with IBS controls. No significant difference was found in the density of any of these cells in the jejunal mucosa of patients compared with IBS controls. CONCLUSIONS: The expression of MAdCAM-1 and OX40 ligand on gut endothelial and OX40+ cells is increased in sites of mucosal inflammation in patients with inflammatory bowel disease. No evidence was found for increased lamina propria T cells or increased vascular adhesion molecule expression in the proximal intestine of patients with distal inflammatory bowel disease. (+info)
Ulcerative colitis patients with a family history of colorectal cancer should be subjected to close and careful surveillance.
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We report two cases affected by neoplasia after colectomy with ileo-rectal anastomosis (IRA) with a positive family history of colon cancer. Case 1, a 41-year-old ulcerative colitis (UC) patient, underwent IRA in 1977. In 1986, biopsies showed high-grade dysplasia. She underwent resection of the rectal stump in 1986. Submucosal invasive carcinoma was found in the surgical specimen. The immunohistological study demonstrated p53 protein overexpression in the neoplastic lesion. Her family history fulfilled the Amsterdam criteria of hereditary non-polyposis colorectal cancer (HNPCC). Case 2, a 47-year-old UC patient, underwent ascending colostomy in 1975 and the following year IRA. Endoscopic mucosal resection (EMR) for a sessile adenoma was performed in 1995 and subsequently polypectomy was performed for the residual tumor. Recurrent adenoma and dysplasia in another area were detected. The immunohistological study demonstrated p53 protein overexpression only in dysplasia. Renal cancer in the right kidney was detected. Resection of the rectal stump with ileal pouch-anal anastomosis (IAA), loop ileostomy and right nephrectomy were performed in 1998. Her mother and her mother's sister had been diagnosed with colon cancer. Only in the dysplastic lesion did we detect microsatellite instability at D5S644. Both cases with neoplasia had two relatives with colorectal carcinoma. In 33 cases with UC who had been followed up, 30 cases (96.8%) without neoplasia had no family history of colorectal carcinoma. These findings suggest that UC patients with a family history of colon cancer should be put under close surveillance. It should also be emphasized that IAA is the procedure of choice for UC patients with this particular condition. (+info)
Identification of a novel mycobacterial histone H1 homologue (HupB) as an antigenic target of pANCA monoclonal antibody and serum immunoglobulin A from patients with Crohn's disease.
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pANCA is a marker antibody associated with inflammatory bowel disease (IBD), including most patients with ulcerative colitis and a subset with Crohn's disease. This study addressed the hypothesis that pANCA reacts with an antigen(s) of microbial agents potentially relevant to IBD pathogenesis. Using a pANCA monoclonal antibody, we have previously identified the C-terminal basic random-coil domain of histone H1 as a pANCA autoantigen. BLAST analysis of the peptide databases revealed H1 epitope homologues in open reading frames of the Mycobacterium tuberculosis genome. Western analysis of extracts from six mycobacterial species directly demonstrated reactivity to a single, conserved approximately 32-kDa protein. Direct protein sequencing, followed by gene cloning, revealed a novel 214-amino-acid protein, an iron-regulated protein recently termed HupB. Sequence analysis demonstrated its homology with the mammalian histone H1 gene family, and recombinant protein expression confirmed its reactivity with the 5-3 pANCA monoclonal antibody. Binding activity of patient serum immunoglobulin G (IgG) to HupB did not correlate with reactivity to histone H1 or pANCA, indicating the complex character of the pANCA antigen. However, anti-HupB IgA was strongly associated with Crohn's disease (P < 0.001). These findings indicate that the 5-3 pANCA monoclonal antibody detects a structural domain recurrent among mycobacteria and cross-reactive with a DNA-binding domain of histone H1. The association of HupB-binding serum IgA with IBD provides new evidence for the association of a mycobacterial species with Crohn's disease. (+info)