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The incidence of postoperative venous thrombosis among patients with ulcerative colitis.

BACKGROUND: Patients with Ulcerative Colitis (UC) have inherent prothrombotic tendencies. It is unknown whether this necessitates the use of additional perioperative anti-thrombotic prophylaxis when such patients require major surgery. METHODS: The postoperative courses of 79 patients with UC undergoing 180 major abdominal and pelvic operations were examined for clinical and radiological evidence of venous thrombosis. Eighteen patients with Familial Adenomatous Polyposis (FAP) having surgery (35 operations) of similar magnitude were also studied. Standard anti-thrombosis prophylaxis was utilised in all patients. RESULTS: Nine patients with UC were clinically suspected of developing postoperative venous thrombosis, but only three (3.8%) had their diagnosis confirmed radiologically (all had a pulmonary embolus). Therefore, the overall postoperative thrombosis rate, on an intention to treat basis, was 1.7% (3/180). No patient with FAP developed significant venous thrombosis. CONCLUSION: Standard perioperative antithrombotic modalities are sufficient to maintain any potential increase in postoperative thrombotic risk at an acceptable level in patients with UC undergoing operative intervention.

Adolescent↗

Chemoprevention of colorectal cancer in ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis (UC) are at greater risk of developing colorectal cancer (CRC) than the general population. Both duration and extent of UC are important risk factors for CRC, as is the presence of primary sclerosing cholangitis, family history of CRC, and (in some studies) early age at diagnosis of UC. Efforts to reduce this risk have focused on colonoscopic surveillance as the best alternative to the more definitive, but less appealing, approach of prophylactic colectomy. However, spurred on by findings in the sporadic CRC literature, there has been a growing interest in a possible role for chemoprevention of CRC in patients with UC. EMPIRICAL STUDIES: Published evidence to date indicates that 5-aminosalicylic acid agents are protective against the development of dysplasia and CRC. Oral, but not topical, steroids also appear to be chemoprotective, but their chronic use cannot be recommended for this indication. Ursodeoxycholic acid has been shown to reduce the risk of neoplasia in UC patients with primary sclerosing cholangitis. Evidence suggests, but does not prove, that folic acid is chemopreventive in patients with UC. Further studies are needed to fully define the chemoprotective role of these and other agents.

Anti-Inflammatory Agents, Non-Steroidal↗

Genomic analysis of a case of multifocal adenocarcinoma in ulcerative colitis.

Long-standing ulcerative colitis is associated with an elevated risk of developing colonic adenocarcinoma. A very limited group of patients present with multiple synchronous cancers. This could be due to either a multifocal presentation of the same neoplastic clone or different tumors arising in a large area of polyclonal dysplastic colonic mucosa ("field cancerization"). Here, we describe a patient with long-standing colitis and three different tumors in the rectosigmoid part of the large bowel. Clonal evaluation of the lesions was performed by array-based comparative genomic hybridization. These three neoplasms showed a comparable pattern of genomic alterations characterized by gains of chromosomes 12, 13, and 20. Noteworthy, dysplastic mucosa distal to the three cancers displayed a completely different pattern of genomic changes indicating that different cell lineages were present. In addition, all three carcinomas were microsatellite stable and revealed identical immunoprofiles for several cancer-associated genes. We conclude that these three multifocal tumors must have originated from the same preneoplastic lineage.

Adenocarcinoma↗

Immune thrombocytopenic purpura in patients with ulcerative colitis.

Extraintestinal manifestations of ulcerative colitis (UC) are well known, but immunologically mediated hematological diseases are relatively rare. We describe two cases of immune thrombocytopenic purpura (ITP) associated with preexisting UC. Our patients had typical symptoms of UC, and endoscopy showed pancolitis. During treatment with 5-aminosalicylic acid and steroids, severe thrombocytopenia was noted. ITP was diagnosed based on a normal to high number of megakaryocytes in the bone marrow, positive autoantibody to platelet membrane antigen, and absence of splenomegaly. Medical treatment, including increased dosage of steroids, failed to control UC and ITP in both patients. In the first patient, the platelet count recovered after colectomy, while the second patient died of a cerebral hemorrhage. We stress that a diagnosis of ITP should be considered for thrombocytopenia in patients with UC, especially those showing extensive and significant colonic inflammation, and that colectomy of UC might resolve resistant ITP.

Adult↗

Pulmonary involvement in ulcerative colitis.

Pulmonary involvement in ulcerative colitis usually presents as a rapidly progressive cough with copious amounts of sputum. Although it is rare, distressing symptoms may be relieved by inhaled steroids in 50-60% of cases. Three case reports are presented along with a review of the features of 28 other cases.

Adult↗

Left-sided ulcerative colitis.

Left-sided ulcerative colitis is not a distinct entity, but a less extensive form of pancolitis. The epidemiologic and genetic characteristics are thought to be analogous. The rate of colorectal cancer, however, seems to be proportional to the extent of disease. Primary treatment for left-sided disease is topical 5-aminosalicyclic acid (5ASA) agents. In patients who do not respond to topical therapy, oral 5ASA agents of differing delivery methods to the distal bowel can be used. There is much debate pertaining to the clinical superiority of the oral 5ASA agents.

Administration, Cutaneous↗

Polypectomy may be adequate treatment for adenoma-like dysplastic lesions in chronic ulcerative colitis.

BACKGROUND & AIMS: Chronic ulcerative colitis (CUC)-associated adenoma-like DALMs (dysplasia-associated lesions or masses) pose a difficult clinical problem to both gastroenterologists and pathologists because they are difficult to distinguish endoscopically and pathologically from sporadic adenomas that develop coincidentally in patients with CUC. The aim of this study was to evaluate the outcome of CUC patients with an adenoma-like DALM treated conservatively and to compare the findings with CUC patients with a coincidental sporadic adenoma. METHODS: Clinical, endoscopic, and pathological features and outcome of 24 CUC patients with an adenoma-like DALM were compared with those of 10 CUC patients with a coincidental sporadic adenoma and 49 non-CUC (control) patients with a sporadic adenoma. Patients were followed up for a mean of 42.4 and 41.2 months for the 2 CUC groups, respectively, and 37.0 months for the non-CUC controls by endoscopic surveillance. RESULTS: Of the 24 CUC patients with adenoma-like DALMs (male/female ratio, 14/10; mean age, 61.5 years; mean duration of colitis, 10.4 years), 14 (58%) developed further adenoma-like DALMs within the follow-up interval. Only 1 patient (4%) developed an isolated focus of low-grade dysplasia, and none developed adenocarcinoma. Five of 10 (50%) CUC patients with sporadic adenomas developed further adenomas, and none of the patients in this group developed either dysplasia or adenocarcinoma. Of the 49 non-CUC control patients, 39% developed further adenomas. CONCLUSIONS: CUC patients who develop an adenoma-like DALM that endoscopically and histologically resembles a sporadic adenoma, regardless of its location (either within or outside areas of documented colitis), may be treated with polypectomy and endoscopic surveillance because of its relatively benign course.

Adenoma↗

Total colectomy with ileo-endomuscular pull-through in the treatment of ulcerative colitis in children.

Since ulcerative colitis is primarily a mucosal disease, total colectomy with rectal mucosectomy and ileo-endomuscular pull-through (Soave) offers many theoretical advantages. The diseased colon is removed, the anal sphincteric mechanism is preserved, and permanent ileostomy is avoided, bladder and sexual function are preserved, and problems with perineal wound healing are avoided. Of critical importance is the state of rectal mucosal disease in the selection of patients for this operation. Our experience with four children in whom the operation has been performed is presented. Postoperative diarrhea has not proved to be a significant problem and continence has been maintained.

Adolescent↗

Ulcerative colitis: an immunological disease?

Ulcerative colitis is an inflammatory disease of the large intestine of unknown aetiology. The nature of the inflammatory infiltrate together with the response to corticosteroids suggests that an abnormal immune response is at work. The key question of whether the immune system is responding to an abnormal breach in the mucosa due to another primary abnormality or whether the primary defect lies within the immune response itself has not been answered. Thus far, it is clear that both T and B cell compartments are involved in the persistence of inflammation but the initial interactions that take place in the mucosa in terms of antigen processing and presentation have not been adequately investigated. Those critical steps and potential defects that push T cells and B cells into a heightened state of activation need to be identified.

Animals↗

Can colectomy cure immune thrombocytopenic purpura in a patient with ulcerative colitis?

The association between ulcerative colitis (UC) and immune thrombocytopenic purpura (ITP) has been suggested by sporadic case reports. Prior reports have focused on the role of medical therapy and/or splenectomy for control of concurrent ITP and UC. We report a case of a patient with UC and ITP who was poorly controlled on maximal medical therapy for these two disorders and underwent a colectomy that cured both diseases.

Adult↗

Idiopathic myelofibrosis associated with ulcerative colitis.

A patient with ulcerative colitis (UC) who developed idiopathic myelofibrosis (IM) is reported. The initial diagnosis of UC was established by colonoscopy and large bowel biopsy, performed after a one-month history of abdominal pain and bloody diarrhea. The patient showed a favorable response to prednisone and mesalamine treatment and six months later he developed a new episode of UC, which was successfully controlled with treatment. However, two years later splenomegaly and anemia were observed, with aniso-poikilocytosis, tear-drop cells, immature myeloid precursors in the peripheral blood, and increased serum LDH, arising the suspicion of IM, a diagnosis that was confirmed by bone marrow biopsy. The present case represents a new association of IM with an autoimmune disease and gives support to the hypothesis of a possible immune basis of some IM cases.

Aged↗

Chemotaxonomic analysis of bacterial populations colonizing the rectal mucosa in patients with ulcerative colitis.

The etiology of ulcerative colitis (UC) is unknown, but evidence links it to bacteria belonging to the normal colonic microbiota. The aims of this study were to characterize bacteria colonizing the rectal epithelium, and to investigate whether significant differences existed in UC. Rectal biopsy specimens were obtained via endoscopy from 9 patients with active colitis and 10 patients without inflammatory bowel disease. Complex bacterial communities colonized the rectal mucosa in all subjects. Overall, 72 bacterial taxa (18 genera) were detected. Twenty species were common to both groups, but only differences in bifidobacteria were statistically significant (P=.005). Peptostreptococci were only detected in patients with UC. Microscopy showed that bacteria in mucosal biofilms often occurred in microcolonies. Interindividual variations in mucosal biofilms made it difficult to assign a role for specific bacteria in UC etiology. However, differences in bifidobacteria and peptostreptococci may implicate these organisms in this disease.

Adult↗

Juvenile polyps and ulcerative colitis.

Four children with ulcerative colitis, three of whom were in clinical remission of their disease, experienced rectal bleeding due to solitary juvenile polyps. Only one of the four polyps was detected radiologically. Two children passed their polyps spontaneously, one was identified at colonoscopy, and the fourth caused colocolic intussusception and was removed during surgery.

Child↗

Distribution of cell populations with DNA aneuploidy and p53 protein expression in ulcerative colitis.

OBJECTIVE: Patients with ulcerative colitis are at an increased risk for developing colorectal neoplasms. p53 mutations and the occurrence of DNA aneuploidies are common events in the development of sporadic colorectal neoplasias. This study tried to determine the frequency of these events during the development of colitis-associated colorectal neoplasms. DESIGN/METHODS: Four colectomy specimens with a total of 124 biopsies were investigated. DNA content was measured by flow cytometry and p53 protein expression was detected by immunohistochemistry. These results were correlated with histological findings. RESULTS: DNA aneuploidies were found in 58 (46.8%), and p53 protein expression in 30 samples (24.2%). The presence of DNA aneuploidy as well as of p53 protein expression correlated with the histological characteristics of neoplastic transformation. In areas without dysplasias or with indefinite dysplasias, 31.5% of the samples showed DNA aneuploidies and in about 9% of the samples p53 protein expression could be detected; 33.7% of samples without or with indefinite dysplasias showed p53 protein expression and/or DNA aneuploidies. CONCLUSION: These results show that the occurrence of DNA aneuploidies and nuclear p53 protein expression is a common event in the development of colitis-associated colorectal neoplasias. p53 protein expression seems to be an early event in this process. DNA aneuploidies occur even earlier and more frequently in the absence of p53 protein expression. Therefore, other genetic alterations besides p53 gene mutations might be involved in colitis-associated tumour development.

Adult↗

Leukocytapheresis is effective in inducing but not in maintaining remission in ulcerative colitis.

GOALS AND BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by dense infiltration of lymphocytes, plasma cells, neutrophils, and monocyte-macrophages into the colonic mucosa. Leukocytapheresis is a procedure for selectively removing white blood cells from withdrawn blood. It is used for the treatment of several autoimmune diseases. This study was performed to evaluate the effectiveness of leukocytapheresis for inducing and maintaining remission in corticosteroid-resistant UC, as compared with corticosteroid-responsive UC. STUDY: Forty-five patients with active UC who were treated with a dose of 1 mg/kg per day or more of prednisolone given systemically for at least 2 weeks were evaluated. Twenty patients (6 males, 14 females) in whom improvement was induced only by high doses of prednisolone were allocated as the corticosteroid-responsive group. The other 25 patients (11 males, 14 females) who did not respond to the above-mentioned dose of prednisolone therapy were allocated as the corticosteroid-resistant group and received leukocytapheresis therapy once a week for 5 weeks. Of patients who had a remission, the corticosteroid-responsive group continued to have the conventional therapy and the corticosteroid-resistant group were given leukocytapheresis once every 4 weeks for at least 2 years as maintenance therapy. RESULTS: Remission was induced by 5 weeks of leukocytapheresis in 23 of the 25 (92%) patients with corticosteroid-resistant active UC. The number of days required to achieve remission of UC was fewer in patients who received leukocytapheresis than in those who did not. Follow-up study of the patients who had remission showed similar relapse rates at 2 years in the patients who received leukocytapheresis and those given high doses of prednisolone alone. CONCLUSIONS: Leukocytapheresis is an effective treatment of acute corticosteroid-resistant UC but does not prevent the recurrence of UC.

Adolescent↗

Association of CTLA-4 gene microsatellite polymorphism with ulcerative colitis in Chinese patients.

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation as a result of an exaggerated T cell response. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4), expressed mainly in activated T cells, inhibits T cell activation and proliferation by combining B7 through competing CD28 and maintains immune homeostasis. Polymorphisms of the CTLA-4 gene are known to be associated with several autoimmune diseases. The aim of this study was to investigate the association between the CTLA-4 gene microsatellite polymorphism and UC in Chinese patients. Unrelated 100 Chinese patients with UC and 140 healthy controls were studied. The (AT) repeats in the 3' untranslated region of exon 4 of the CTLA-4 gene were amplified by allele-specific polymerase chain reaction (PCR). The amplified products were electrophoresed on a 12% polyacrylamide gel, followed by silver staining. Twenty alleles were found in Chinese patients and healthy controls. The 122-bp allele was increased in UC compared with healthy controls (9.5% vs 0.7%, P = 0.0001/Pc = 0.002, OR = 14.591, 95%CI 3.357-63.420). The frequency of the longer alleles (>or=118 bp) of UC was higher than that in healthy controls (26% vs 4%, P = 0.0001/Pc = 0.0002, OR = 7.644, 95%CI 3.950-14.792), but was not associated with location and severity of the disease. Furthermore, the longer alleles were not associated with haplotypes of C-318T/A+49G of the CTLA-4 gene in Chinese patients with UC. The longer alleles of the CTLA-4 gene microsatellite polymorphism were strongly associated with UC in Chinese patients.

Adolescent↗

Mutations of p53 in morphologically non-neoplastic mucosa of long-standing ulcerative colitis.

Two cases of ulcerative colitis (UC)-associated carcinoma or dysplasia and morphologically non-neoplastic mucosa with p53 protein overexpression (MNNM-p53OE) were selected. DNA was extracted from the paraffin blocks of these lesions and exons 5 - 8 of the p53 gene were analyzed by PCR and direct sequencing. In addition, mutations in K-ras codon 12 were analyzed by PCR-RFLP methods. MNNM-p53OE was located surrounding and adjoining a coexisting carcinoma and / or dysplasia. A p53 mutation was detected in 12 / 22 (54.5%) MNNM-p53OE samples, 4 / 8 (50%) dysplasia samples and 8 / 8 (100%) carcinoma samples. The p53 mutations detected in MNNM-p53OE were identical to those demonstrated in the adjoining carcinoma and / or dysplasia. No K-ras codon 12 mutation was detected in any of the samples. These results indicate that MNNM-p53OE may share an identical clonal linkage with a coexisting carcinoma and / or dysplasia, and may be an initial and submorphological form of UC-associated neoplasia. Recognition of MNNM-p53OE in biopsy specimens may help to identify patients with UC at risk of developing colorectal carcinoma.

Adult↗

Review article: how and when to use ciclosporin in ulcerative colitis.

Although colectomy for ulcerative colitis is curative, long-term quality of life is reduced. Intravenous ciclosporin 4 mg/kg/day has significant toxicity. There is now evidence that low-dose ciclosporin (2 mg/kg daily by intravenous infusion, or 5-6 mg/kg daily in a twice daily oral dosage) has an acceptable safety profile, even when used in combination with corticosteroids. Drug dosage should be adjusted to the levels of 150-250 ng/mL initially (random levels during intravenous infusion, or trough levels for oral use). Ciclosporin should be considered not only in those who have failed 7 days of corticosteroids, but also in fulminant colitis at day 3, if not responding to corticosteroids. The drug should be avoided in frail or elderly patients with significant comorbidity, and also where colectomy is likely to be necessary in the short to medium term. Ciclosporin should not be continued for more than 7 days, unless there is a definite response. A 70-80% initial response is likely, and responders are discharged on oral ciclosporin, adding thiopurines and tailing prednisolone rapidly. The drug should be continued for 3 months. The likelihood of avoiding colectomy over 2-3 years is 40-50%. More studies are needed to evaluate the use of oral ciclosporin in corticosteroid-refractory colitis in out-patients, and to assess whether monotherapy (without corticosteroids) is significantly safer, without loss of efficacy.

Administration, Oral↗