S. C. Truelove

Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres.

A retrospective cohort of 823 patients with ulcerative colitis who resided at the time of diagnosis in one of three defined geographical areas (West Midlands region, Oxford region, England and Stockholm County, Sweden) was assembled. The patients were first seen at named hospitals in these areas and the diagnosis of ulcerative colitis established within five years of onset of symptoms between 1945-1965. All patients were 15 years of age or more at onset of disease and were followed for a minimum of 17 years and a maximum of 38 years. Ninety seven per cent completeness of follow up was achieved. Examining the colorectal cancer risk in the series relative to the risk in the general population by standardised morbidity ratios, there was an eight fold increased risk of cancer in the series as a whole. Dividing the series by extent of colitis, extensive colitis patients showed a 19 fold increase in risk. A four fold increased risk was shown in the remainder of the series (left sided colitis, proctitis and extent unknown). Life table analyses in extensive colitis gave cumulative risks of 7.2% (CI 3.6-10.8) at 20 years from onset of disease and 16.5% (CI 9.0-24.0) at 30 years from onset. No significant effect of age at onset, sex or referral centre could be detected. Examination of the data by interval from onset to cancer and by actual age at development of cancer suggests that patients who develop colorectal cancer will do so in a distribution around 50 years of age independent of duration of disease in adult onset ulcerative colitis (greater than 15 years at onset of disease). An inverse relationship was shown between age at onset of disease and interval from onset of disease to cancer. Further age specific rates for cancer increased up to 50 years and decreased thereafter. These results suggest that extensive colitis patients have a genetic predisposition to colorectal cancer and that longstanding inflammation is not of primary importance in the initiation/promotion of cancer in this disease.

INTENSIVE INTRAVENOUS REGIMEN FOR SEVERE ATTACKS OF ULCERATIVE COLITIS

Abstract A 5-day intensive intravenous regimen for the treatment of severe attacks of ulcerative colitis has been developed, and the results in forty-nine patients treated in this way in a 5-year period are described. Thirty-six patients were in complete remission at the end of the 5-day course. Four showed clinical improvement without remission, and they all required urgent surgery within the next 6 weeks. The remainder were unchanged by the intravenous regimen and required emergency surgery. This regimen gives a higher remission-rate than has been recorded previously, and failure to respond provides a simple and straightforward indication for surgery without further delay. When used in the treatment of first attacks of the disease, the regimen gives a considerable chance of a prolonged remission. Two-thirds of the first-attack patients who went into remission remained symptom-free during the period of follow-up, which averaged more than 3 years.

Azathioprine in ulcerative colitis: final report on controlled therapeutic trial.

Eighty patients, all of whom were suffering from a frank clinical attack of ulcerative colitis, were admitted to the trial. The attack was treated with a standard course of corticosteroids and the patients were immediately placed on treatment with either azathioprine in a dose of 2·5 mg/kg body weight or dummy tablets. The trial tablets were continued for one year while the patients were maintained under regular clinical, sigmoidoscopic, histological, haematological, and biochemical surveillance. If a patient relapsed during such maintenance treatment he or she was treated with a further course of corticosteroids without interrupting maintenance treatment. In the treatment of an actual attack of ulcerative colitis the results in the attacks which brought the 80 patients into the trial show that no benefit came from the addition of azathioprine to a standard course of corticosteroid therapy. Patients admitted in their first attack of ulcerative colitis showed no benefit from the one-year maintenance treatment with azathioprine, the benefits of which were confined to patients admitted in a relapse of established disease. Even in these the difference between the treated group and the control group failed to reach statistical significance, but the difference was big enough to suggest that there is a prima facie case for regarding azathioprine as of some benefit in this group of patients.

Split ileostomy and ileocolostomy for Crohn's disease of the colon and ulcerative colitis: a 20 year survey.

The clinical course of 140 patients who have had a split ileostomy for ulcerative colitis or colonic Crohns disease over a 20 year period is reported. In 37 patients with ulcerative colitis there was no sustained improvement. In the 102 patients with Crohns disease there was an immediate clinical improvement in 95, which was sustained in 65. Thirty patients have subsequently required a proctocolectomy for persistent inflammation, and 28 are still defunctioned. Bowel continuity was restored after 61 split ileostomies and in 44 patients intestinal continuity remains intact at the present time (mean follow up since closure = 62.5 months, range 0-231 months). It is concluded that a split ileostomy is a safe conservative operation producing at least temporary improvement in severely ill and malnourished patients with Crohns colitis, and that if a subsequent resection becomes necessary it may be less extensive than was thought applicable at the initial operation. In 27 patients a resection has not been required.

Circulating antibodies to cow's milk proteins in ulcerative colitis

Sera from patients with ulcerative colitis (51), Crohns disease (30), hypolactasia (13), untreated adult coeliac disease (11), irritable colon syndrome (24), and sera from 38 healthy control subjects were tested for antibodies to the principal cows milk proteins—casein, α-lactalbumin, and β-lactoglobulin. The red-cell-linked antigen-antiglobulin reaction was used to determine the titres of direct agglutinating antibodies and IgA and IgG incomplete antibodies. Apart from patients with coeliac disease, direct agglutinating antibodies were found infrequently and then in low titres. Approximately 50% of subjects had low titres of IgA and IgG antibodies. However, the titres found in sera from patients with ulcerative colitis did not differ from those found in the control subjects or in patients with Crohns disease, hypolactasia, or irritable colon syndrome. Patients with untreated coeliac disease frequently had high antibody titres to the milk proteins. In all subjects tested, incomplete antibodies of IgA or IgG immunoglobulin class occurred with equal frequency. The frequent occurrence in adults of low titres of antibodies to the milk proteins may be due to continued absorption of minute amounts of protein. Absorption of allergens may be facilitated by mucosal damage, such as that of coeliac disease, with stimulation of antibody production. At the present time, however, there is little evidence to suggest that milk allergy is a factor in the aetiology of ulcerative colitis.

Reaginic hypersensitivity in ulcerative colitis

Reaginic hypersensitivity in ulcerative colitis has been investigated in respect of a hypersensitivity to the cows milk proteins and the frequency of atopic asthma, hay fever, and eczema. Intradermal tests were frequently positive, especially to casein, but the results did not differ from those found in healthy individuals and in groups of patients with Crohns disease, hypolactasia, and the irritable colon syndrome. No circulating IgE-specific antibodies to the milk proteins were found. An increased frequency of atopic diseases was found in patients suffering from ulcerative colitis (15·7%) and Crohns disease (13·3%) compared with the findings in a control group (1·2%). It is concluded that, if an allergy to milk proteins is a factor in the pathogenesis of ulcerative colitis, it is not mediated by reaginic antibodies. It is possible, however, that the frequent occurrence of atopy indicates a susceptibility to develop reaginic responses even though this mechanism does not apply to the milk proteins.

Azathioprine in Ulcerative Colitis : An Interim Report on a Controlled Therapeutic Trial

This interim report on a controlled therapeutic trial of azathioprine in ulcerative colitis deals with the first 40 patients to complete a one-year period of maintenance treatment with azathioprine or with dummy tablets. The patients all suffered from classical ulcerative colitis and were in an actual attack of the disease at the time of admission. The attack was treated with a standard corticosteroid regimen and the patients were assigned at random to maintenance treatment with real or dummy azathioprine tablets, using a stratified design. The treatment and control groups were closely similar at the beginning of the trial. The effect of treatment has been assessed on the basis of the number of relapses of the disease occurring during the one-year trial period, supplemented by an assessment of the sigmoidoscopic picture and of the histological findings on serial rectal biopsy. In the patients receiving azathioprine the disease ran a more favourable course than in the control group. After the attack had been treated 11 of the 20 patients on azathioprine were symptom-free throughout the rest of the one-year trial period compared with only 5 out of 20 in the control group. The only three patients classed as failures were all in the control group. These differences just fail to reach conventional levels of statistical significance. Azathioprine is not dramatically successful but may still be a useful addition to the medical treatment of ulcerative colitis, particularly if conventional medical treatment is ineffective and there are reasons for wishing to avoid radical surgery. In the dose used azathioprine was virtually free from undesirable side effects.

Benign intracranial hypertension and ulcerative colitis

A case of benign intracranial hypertension, occurring in association with ulcerative colitis, is described. The pathogenesis of the intracranial hypertension is uncertain but it is possible that intracranial thrombosis affecting small venous radicles was the responsible mechanism.ConclusionA case of benign intracranial hypertension, occurring in association with ulcerative colitis, is described. The pathogenesis of the intracranial hypertension is uncertain but it is possible that intracranial thrombosis affecting small venous radicles was the responsible mechanism.