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PubMed2004

Ulcerative colitis: conservative management and long-term effects.

Ulcerative colitis is characterized by chronic inflammation of the colon. Typical symptoms are diarrhoea, rectal bleeding, abdominal pain and fever. The aetiology of the disease is unclear. The inflammation can be localized in the rectum or can extend to the left side or the whole colon. Treatment for induction and remission maintenance depends on the severity and extension of mucosal inflammation. Topical 5-aminosalicylates have been shown in studies to be the treatment of choice in mild to moderate ulcerative colitis. Oral 5-aminosalicylates can be used in distal, mild and moderate ulcerative colitis and for remission maintenance. For patients with a more extended or severe inflammation, oral or i.v. corticosteroids should be used. Patients with severe and/or chronic disease require immunosuppressive therapy with azathioprine or 6-mercaptopurine. For patients with severe, chronic, refractory disease, cyclosporine i.v. can be used. If no response to treatment is seen, proctocolectomy should be considered. Biological agents such as beta-Interferon seem to be effective in mild to moderately ulcerative colitis, but further studies have to be performed.

Administration, Oral↗

PubMed1993

Primary biliary cirrhosis associated with ulcerative colitis.

Hepatobiliary diseases are frequently associated with ulcerative colitis. The most commonly reported syndromes are primary sclerosing cholangitis, chronic active hepatitis and cirrhosis. Recently, the association of primary biliary cirrhosis and ulcerative colitis has been reported. We present a case of primary biliary cirrhosis in a young man with left-sided ulcerative colitis and review the previous reported cases, noting some unique similarities between them.

Adult↗

PubMed1993

Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease.

The perpetuation of inflammation in ulcerative colitis and Crohn's disease may be regulated in part by an increased secretion of proinflammatory cytokines due to either an appropriate response to initial stimulating agents, and/or due to an impaired down-regulation of cytokine secretion. The aim of this study was to determine the secretion patterns of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-1 beta, from isolated lamina propria mononuclear cells (LPMNC) isolated from colonic biopsies from patients with untreated ulcerative colitis or Crohn's disease. LPMNC isolated from involved inflammatory bowel disease (IBD) mucosa spontaneously produced increased amounts of TNF-alpha, and IL-6, and IL-1 beta. The TNF-alpha secretion from IBD LPMNC could be further enhanced by pokeweed mitogen stimulation. The secretion patterns of TNF-alpha and IL-1 beta by LPMNC from patients with either ulcerative colitis or Crohn's disease demonstrated a close correlation with the degree of tissue involvement and mucosal inflammation. LPMNC from non-involved ulcerative colitis mucosa secreted markedly increased levels of IL-6 compared with non-involved Crohn's disease mucosa or control mucosa. The heightened IL-6 secretion from LPMNC from non-involved ulcerative colitis mucosa without visible or microscopic signs of inflammation indicates that the pathophysiologic mechanisms involved in the initiation of inflammation may differ between ulcerative colitis and Crohn's disease. The determination of proinflammatory cytokine secretion by isolated LPMNC from colonoscopic biopsies may be a sensitive method for monitoring the severity of mucosal inflammation in IBD patients.

Adult↗

PubMed1998

Factors related to the presence of IgA class antineutrophil cytoplasmic antibodies in ulcerative colitis.

OBJECTIVES: Few studies have assessed the IgA antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis patients and there is no information about factors related to its synthesis and its status after colectomy. The aims of the study were to assess the serum IgA ANCA prevalence in ulcerative colitis patients, both nonoperated and operated, and to determine the clinical factors related to this positivity. METHODS: Fifty-four ulcerative colitis patients, 63 ulcerative colitis colectomized patients (32 with Brooke's ileostomy and 31 with ileal pouch anal anastomosis), and 24 controls were studied. Antineutrophil cytoplasmic antibodies were detected by specific indirect immunofluorescent assays. RESULTS: The percentage of IgA ANCA was significantly higher in patients with ileal pouch anal anastomosis (45%) than in patients with Brooke's ileostomy (22%). There were no differences related to the presence of pouchitis in ileal pouch anal anastomosis patients. Patients with nonoperated extensive colitis (47%) had a significantly higher percentage of IgA ANCA than patients with proctitis (19%). Total percentage of ANCA (IgA and/or IgG) tended to be higher in ulcerative colitis and in patients with ileal pouch anal anastomosis than in patients with Brooke's ileostomy. However, in ileal pouch anal anastomosis patients, ANCA positivity was mainly due to exclusive IgA production. CONCLUSIONS: A substantial percentage of ulcerative colitis patients, and especially colectomized patients with ileal pouch anal anastomosis, had IgA ANCA, suggesting that ANCA production in ulcerative colitis might be stimulated by an immune reaction in the intestinal mucosa.

Adult↗

PubMed2001

Low molecular weight heparin treatment in steroid refractory ulcerative colitis: clinical outcome and influence on mucosal capillary thrombi.

BACKGROUND: In ulcerative colitis, a state of hypercoagulation has frequently been observed. Unfractionated heparin has shown beneficial effects as an adjuvant treatment of steroid refractory ulcerative colitis in open trials and in one placebo-controlled trial. Low molecular weight heparin (LMWH) offers advantages in the method of administration, but it has not been evaluated in severe ulcerative colitis. We therefore assessed the tolerability, safety and potential therapeutical effects of LMWH in hospitalized patients with steroid refractory ulcerative colitis. METHODS: Twenty-five patients with severely active ulcerative colitis were included in an open-labelled trial. All patients had a flare-up of disease under glucocorticosteroid treatment. Nadroparine calcium 5.700 IE anti-Xa/0.6 mL s.c. was self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events, and changes in clinical symptoms and in laboratory, endoscopical and histological results were analysed. RESULTS: Tolerability and compliance were excellent and no serious adverse events occurred. In 20 of 25 patients, a good clinical and laboratory response was observed. Also, the endoscopic and histological signs of inflammation were found to be significantly improved. However, this was not accompanied by a significant reduction in the number of mucosal microvascular thrombi after 8 weeks of LMWH treatment. CONCLUSION: LMWH may be a safe adjuvant therapy for patients with active, glucocorticosteroid refractory ulcerative colitis.

Anticoagulants↗

PubMed2003

Alternative approach to massive gastrointestinal bleeding in ulcerative colitis: highly selective transcatheter embolization.

Massive haemorrhage in ulcerative colitis mainly occurs as a result of exacerbated disease, usually acute or even fulminant colitis. Emergency proctocolectomy is currently advocated as the only reliable treatment of this patient group. However, this type of surgical intervention has a high rate of morbidity and mortality. Recently, several promising studies have been published that describe transcatheter embolization for the treatment of massive lower gastrointestinal bleeding in cases of bleeding colonic diverticular disease and angiodysplasia. Success rates of 48-88% have been reported. To avoid the high risk associated with emergency colectomy, this modern procedure was performed in an ulcerative colitis patient with intractable lower gastrointestinal bleeding. To our knowledge, this is the first patient with ulcerative colitis presenting with massive lower gastrointestinal blood loss to be successfully treated by highly selective transcatheter embolization. This interventional procedure is suggested as an alternative therapeutic approach to haematochezia in selected ulcerative colitis patients.

Colitis, Ulcerative↗

PubMed1982

Preserving the ascending colon as an alternative surgical option in ulcerative colitis.

Six patients with ulcerative colitis were studied to assess the histologic appearance of the ascending colon which was preserved at the initial operation performed more than ten years previous. Inflammatory cells were increased in all patients, but ulceration was not present microscopically. Most patients had less than five bowel movements a day. Because of good long term survival of the mucosa, wider use of a surgical approach is proposed, based upon excising the colonic mucosa most prone to ulceration and metabolic derangement. The procedure entails subtotal colectomy, mucosectomy of the rectal mucosa and preservation of the ascending colon as a neorectum. Prime advantages are the lack of a stoma and fewer bowel movements than result from other operations.

Adult↗

PubMed1990

Surgical alternatives for ulcerative colitis.

There is no medical cure of ulcerative colitis except for the removal of the entire large intestine, or at least its mucosa. It is unknown as to what percentage of patients with ulcerative colitis present for surgical correction, and the potential for surgery in turn usually is related to the extent of large intestine involved. This article explores new alternatives that are available so that proctocolectomy and ileostomy are no longer the sole option for patients with ulcerative colitis.

Anastomosis, Surgical↗

PubMed1990

Why do patients with ulcerative colitis relapse?

To determine the factors responsible for ulcerative colitis relapse a cohort of 92 patients (18 to 78 years, 50 men) with clinically inactive disease have been followed for over 48 weeks. At 12 weekly intervals patients were asked, by means of standardised questionnaires, about infections, compliance with maintenance medication, new drug treatment, dietary changes, episodes of non-bloody diarrhoea, life stresses, and feelings of anxiety and depression. Thirty five patients (38%) relapsed (median interval 17 weeks, range three to 46 weeks). Patients who relapsed had a higher previous relapse rate than non-relapsers (p less than 0.001) and a shorter time from previous relapse to trial entry (p less than 0.05). Other clinical characteristics were equally matched in the two groups. Between and within group comparisons revealed that upper respiratory tract symptoms, antibiotic ingestion, analgesic intake, diarrhoeal episodes and stressful life events were no more common in the four weeks before relapse than before routine attendance. Anxiety and depression ratings were also similar in the two groups. The timing of ulcerative colitis relapse showed a clear seasonal pattern with 26 patients relapsing from August to January and only nine from January to July (p less than 0.001). In addition, a retrospective case note analysis revealed significant seasonality of onset of ulcerative colitis. We conclude that seasonal factors may contribute to both onset and relapse of ulcerative colitis.

Adolescent↗

PubMed1994

Management of fulminant ulcerative colitis by primary restorative proctocolectomy.

UNLABELLED: Severe acute ulcerative colitis unresponsive to medical management is characterized by multiple associated risk factors including anemia, hypoproteinemia, and high steroid requirements when urgent surgery is required. Current surgical options include use of primary ileal pouch-anal anastomosis (IPAA) vs. historic trends favoring colectomy with ileostomy. PURPOSE: To evaluate the efficacy of primary IPAA in patients with severe colitis, we reviewed our own experience in 20 patients with this condition. METHODS: Patients undergoing primary restorative proctocolectomy included 13 males and 7 females (mean age, 30.5 +/- 2.4 years). Exclusion criteria for primary reconstruction included septic patients and patients with associated medical conditions such as pulmonary or cardiovascular disease. History of ulcerative colitis averaged 3.1 +/- 1.1 years (range, 1 month to 19 years). Preoperative mean total serum protein concentration was 5.0 +/- 0.2 g/dl, and mean albumin concentration was 2.1 +/- 0.2 g/dl, reflecting disease severity. The average daily steroid requirement at the time of urgent colectomy was 58.0 +/- 4.4 mg of prednisone (or intravenous equivalent). Primary IPAA included 18 "W" reservoirs, 1 "S" reservoir, and 1 "J" reservoir. RESULTS: Major surgical complications included mild pancreatitis (10 percent), anastomotic leak (5 percent), adrenal insufficiency (15 percent), an upper gastrointestinal bleed (5 percent), and small bowel obstruction (15 percent). There were no deaths, and no patients developed pelvic sepsis or required IPAA removal. At three and twelve months, 24-hr stool frequency averaged 7.3 +/- 0.4 and 4.9 +/- 0.3, respectively. Overall day and night continence was excellent and not different from patients who underwent elective IPAA procedures for ulcerative colitis. CONCLUSIONS: Improved options such as primary IPAA may be safely used in selected patients requiring urgent surgery for severe or fulminant ulcerative colitis. Medical management should be abbreviated when disease control cannot be promptly achieved.

Acute Disease↗

PubMed1996

Operations in unselected patients with ulcerative colitis and indeterminate colitis. A long-term follow-up study.

OBJECTIVE: To assess the need for operative treatment for ulcerative colitis and indeterminate colitis. DESIGN: Retrospective study. SETTING: University Hospital, Sweden. SUBJECT: All patients diagnosed from 1958 to 1982, in Malmö, Sweden-ulcerative colitis (n = 471) and indeterminate colitis (n = 100). MAIN OUTCOME MEASURES: Incidence of colectomy. RESULTS: The mean follow-up was 15 years. The incidence of colectomy was 7.51, 1.90 and 36.13/1000 person years for definite ulcerative colitis, probable ulcerative colitis and indeterminate colitis, respectively. The incidence of colectomy in patients with definite ulcerative colitis in the present study was low compared with other studies. In contrast to other reports, men had a threefold risk while extent of inflammation did not influence the incidence. Patients with indeterminate colitis were a high risk group with a high incidence of colectomy. The high incidence among patients with indeterminate colitis compared with that in patients with definite ulcerative colitis was also seen in subgroups such as patients with total colitis at diagnosis, in patients in remission after the first attack, and in patients with a severe attack. CONCLUSION: As patients with indeterminate colitis seem to be at increased risk of colectomy it could be important to distinguish them from those with ulcerative colitis. Today, however, it is not possible to identify all patients with indeterminate colitis early in the course of the disease.

Adolescent↗

PubMed1983

Increased oxidation of a chemical carcinogen, benzo(a)pyrene, by colon tissue biopsy specimens from patients with ulcerative colitis.

Colonic biopsy specimens from patients with ulcerative colitis and normal subjects were studied for the ability to metabolize an environmental carcinogen, benzo(a)pyrene. Approximately 73% of 30 colonic biopsy specimens from 7 ulcerative colitis patients could metabolize benzo(a)pyrene to oxidized products, with an average production of 11.6 nmol/mg biopsy protein. In contrast, 39% of 23 biopsy specimens from 5 normal persons showed metabolic activity, with an average of 2.79 nmol benzo(a)pyrene metabolites/mg biopsy protein. Thus, benzo(a)pyrene oxidation activity in colonic tissue from colitis patients was, on the average, fourfold greater than that in normal subjects. This elevated metabolic activity appeared to be unrelated to the state of inflammation in the biopsy section. There was a tendency toward increased metabolic activity in the distal colon. Although there is no evidence that benzo(a)pyrene itself is "the colon carcinogen," this chemical belongs to a broad class of environmental carcinogens, the polycyclic aromatic hydrocarbons. Our findings suggest that the colonic mucosa of patients with ulcerative colitis has a greater ability than that of normal subjects to oxidize such chemicals possibly to electrophiles with higher mutagenic potential.

Adult↗

PubMed1999

[The concept, criteria for diagnosis, and disease classification of ulcerative colitis].

The concept of ulcerative colitis(UC) in Japan has been defined based on the definition of idiopathic proctocolitis by CIOMS. UC is an idiopathic, non-specific inflammatory disorder involving primarily the mucosa and submucosa of the colon, especially the rectum, often with mucosal erosions and ulcers. Criteria for diagnosis of UC consist of the following three conditions; one is continuous or repeated findings of hematochezia or mucous and bloody stools, second is colonoscopic and/or X ray findings characteristic of UC, and third is histopathological findings consistent with UC pathology. Disease classifications of UC are divided in many clinical aspects such as disease extents, disease activity, disease severity, clinical courses, endoscopic grades, and disease conditions for obtaining financial supports by Japanese government.

Colitis, Ulcerative↗

PubMed2006

Basiliximab for the treatment of steroid-resistant ulcerative colitis: further experience in moderate and severe disease.

BACKGROUND: Preliminary data have suggested that interleukin-2 receptor blockade with basiliximab may increase steroid sensitivity. We have previously reported a small case series demonstrating the potential of basiliximab as a novel agent for the treatment of steroid-resistant ulcerative colitis. AIM: To report further experience of the efficacy and safety of treatment with the interleukin-2 receptor blocking monoclonal antibody basiliximab, in addition to steroids, for the treatment of severe and moderate steroid-resistant ulcerative colitis. METHODS: Twenty patients were enrolled - 13 patients with moderate steroid-resistant ulcerative colitis (Ulcerative Colitis Symptom Score: >or=6) and seven patients with severe steroid-resistant ulcerative colitis. All were given a single dose of 40 mg basiliximab plus standard steroid therapy in an open-label, uncontrolled trial. Primary end point was clinical remission within 8 weeks (Ulcerative Colitis Symptom Score: <or=2). RESULTS: Within 8 weeks, 10 of 20 (50%) patients achieved clinical remission (seven of 13 moderate, and three of seven severe). At 24 weeks, 13 of 20 (65%) patients were in clinical remission. Five patients required colectomy (four severe, one moderate ulcerative colitis) and one required rescue ciclosporin (moderate ulcerative colitis). Two patients developed herpes zoster, but treatment was generally well tolerated. CONCLUSIONS: Basiliximab appears to promote prolonged remission after a single treatment. Taken in combination with previously reported data, basiliximab shows particular promise in moderate steroid-resistant ulcerative colitis.

Adolescent↗

PubMed1998

Familial predisposition for colorectal cancer in chronic ulcerative colitis: a case-control study.

BACKGROUND & AIMS: Familial predisposition as a risk for colorectal cancer in ulcerative colitis has not been rigorously explored. The aim of this study was to compare colorectal cancer frequency among kindreds of patients who had ulcerative colitis and colorectal cancer with that of control patients who had ulcerative colitis but no cancer. METHODS: Questionnaires were mailed to subjects to assess cancer occurrence among relatives. Eligible cases included 174 ulcerative colitis patients with colorectal cancer seen at Mayo Clinic in 1976-1994; 174 contemporaneous ulcerative colitis controls without cancer were matched on birth year, sex, and extent and duration of colitis. RESULTS: The responding 147 case and 150 control subjects reported on 1044 and 1090 first-degree relatives, respectively. Colorectal cancer occurred in 14.3% case kindreds and 6.7% control kindreds (P = 0.03). By logistic regression, a family history of sporadic colorectal cancer was an independent risk factor for cancer in ulcerative colitis (odds ratio, 2.33; 95% confidence interval, 1.06-5.14; P = 0.03). CONCLUSIONS: A familial association exists between colorectal cancers occurring with ulcerative colitis and those in the general population. Colorectal cancer in persons with ulcerative colitis represents a risk factor for colorectal cancer in their noncolitic relatives. Likewise, a family history of sporadic colorectal cancer increases the risk of colorectal cancer with ulcerative colitis.

Adult↗

PubMed1996

Risk of relapse in new cases of ulcerative colitis and indeterminate colitis.

PURPOSE: Changes in morbidity pattern of ulcerative colitis have created a need to update understanding of the course of the disease. METHOD: A follow-up study was done of relapse rates and progression of inflammation in 571 non-selected patients with ulcerative and indeterminate colitis. RESULTS: Relapse rate ten years after diagnosis was 70 percent in definite ulcerative colitis, 22 percent in probable ulcerative colitis, and 77 percent in indeterminate colitis. During the study period, there was no change in the relapse rate. In relapsing proctitis, 52 percent developed more extensive inflammation. Fifty-four percent of patients with only one attack of colitis had persistent signs of inflammatory bowel disease. CONCLUSIONS: Shift in morbidity pattern to a greater proportion of patients with proctitis at diagnosis and a shorter time from onset of symptoms to diagnosis had no influence on the relapse rate. Indeterminate colitis has a worse prognosis than definite ulcerative colitis. Considering the documented efficacy of sulfasalazine, the high relapse rate calls for studies of the effectiveness of such treatment in everyday practice.

Adolescent↗

PubMed1993

[Long-term prognosis of patients with ulcerative colitis].

A regional inception cohort of 1161 ulcerative colitis patients was followed from diagnosis to the end of 1987. Follow-up rate for death and occurrence of cancer was 99.9%. Median observation time 11.7 years, range 0-26 years. One hundred and forty-one deaths were observed, 26 due to ulcerative colitis or complications thereof. No significant excess mortality was found after the first year, but in the year of diagnosis the relative risk of death was 2.4 (p < 0.001). The cumulative colectomy rate was 32.4% 25 years after diagnosis. The initial extent of disease significantly influenced the colectomy probability, being 35% in total colitis, 19% in substantial colitis and 9% in distal colitis within the first five years after diagnosis. Six patients developed colorectal cancer within the observation period. Compared to the expected number of 6.6 the relative risk for patients with ulcerative colitis was 0.9. The calculated cumulative cancer incidence was 3.1% after 25 years (95% confidence limits 0.0-6.8). The calculated lifetime risk (0 to 74 years) for development of colorectal cancer was 3.5% for the patients compared to 3.7% for the Danish population. We conclude that with an active approach to medical and surgical treatment as was practiced here, those patients who are left with their colon intact bear no significantly increased risk of colo-rectal malignancy.

Adolescent↗

PubMed1992

Randomised comparison of olsalazine and mesalazine in prevention of relapses in ulcerative colitis.

Sulphasalazine extends remissions and lessens disease activity during relapses of ulcerative colitis, but it also causes many adverse side-effects. The adverse reactions are mostly attributable to the sulphapyridine carrier moiety rather than the active principle 5-aminosalicylic acid (5-ASA), so agents to deliver 5-ASA to the colon by other means have been designed. We have compared the efficacy and tolerability of two such agents, olsalazine and mesalazine, in maintenance therapy of ulcerative colitis. 100 patients with ulcerative colitis in remission were recruited at one centre and assigned randomly to treatment with olsalazine (Dipentum; 1.0 g daily) or mesalazine (Asacol, with Eudragit-S coating; 1.2 g daily). Compliance, biochemical and haematological variables, and clinical evidence of disease activity were assessed every 3 months for 12 months by observers unaware of treatment allocation. In intention-to-treat analysis, which included as treatment failures patients withdrawn for protocol violations, adverse reactions, intercurrent illness, or non-compliance as well as those with relapses of ulcerative colitis, the olsalazine group had a significantly lower rate of treatment failure than the mesalazine group (12/49 [24%] vs 23/50 [46%]; p = 0.025). Analysis restricted to 64 patients still in remission at 1 year and 18 with relapses also showed a significant difference in relapse rate (olsalazine 5/42 [12%] vs mesalazine 13/40 [33%]; p = 0.024). Both drugs were well tolerated; only 9 patients reported substantial side-effects. Olsalazine was clearly superior to mesalazine in prevention of relapses in ulcerative colitis, especially in patients with left-sided disease.

Adolescent↗