Cancer in inflammatory bowel disease.

There is convincing evidence that patients with ulcerative colitis carry a higher risk of developing colorectal cancer than the general population. This risk is as high as 19-fold that in the general population. The results of the Birmingham study (Gut 1988, 29, 206-217) suggest that extensive colitis patients have a genetic predisposition for colorectal cancer and that long-standing inflammation is not of primary importance in the initiation/promotion of cancer in this disease. Population-based studies, although difficult to carry out, should be the epidemiologic method of choice for determining the risk of cancer in future studies.

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.

Crohn's disease in the elderly.

The natural history of Crohn's disease in 47 patients, 60 years of age or older at the time of diagnosis has been defined, and their clinical management and long term prognosis reviewed. Distal colonic involvement is common in this group while extensive colonic and diffuse small bowel disease is rare. Distal colonic involvement usually carries a good prognosis except for those few patients who present with perforation which accounts for most of the disease related mortality. The pattern of distal ileal disease is similar to that observed in the younger patients except for the acute nature of symptoms at first presentation, and the low recurrence rates after initial surgical resection.

Survival of patients with colorectal cancer complicating ulcerative colitis.

The crude five year survival of patients with colorectal cancer complicating ulcerative colitis in a large series of patients under long term review has, for the first time, been compared with the survival of patients with colorectal cancer in the general population (West Midlands region) from which the colitic patients were drawn. Thirty five cases of colorectal cancer were diagnosed in 676 patients with ulcerative colitis between 1944 and 1976. An actuarial five year survival curve was computed for the colitic and non-colitic patients with colorectal cancer. In ulcerative colitis patients with cancer the five year survival was 33.5% (range 16.9-50.1%) compared with 32.6% (28.2-37.0%) in the non-colitic cancer patients drawn from the relevant general population. Overall the prognosis is much better than earlier reports suggest. It is perhaps disappointing that in a closely monitored group the outcome is only as good as that in the general population. Surveillance programmes should improve the outcome in those patients with ulcerative colitis who accept the need for regular review.

Ulcerative colitis: why is the mortality from cardiovascular disease reduced?

A recent mortality study of patients with ulcerative colitis showed significant deficits in deaths from cardiovascular disease and from respiratory disease in males. The reasons for the observed deficits have been examined by studying the risk factors in a consecutive series of 103 patients with ulcerative colitis using matched controls. The patients and controls were assessed for age, sex, social class, alcohol and tobacco consumption. Height, weight and blood pressure were recorded and fasting blood samples were taken for serum lipid estimation. Patients with ulcerative colitis had significantly lower systolic and diastolic blood pressures and the changes were particularly marked in patients with extensive colitis and after panproctocolectomy. After matching for age, sex and social class the patients with ulcerative colitis smoked significantly less than controls. Serum lipid measurements were similar in both groups. The lower blood pressure may be related to sodium and water depletion particularly in ileostomy patients and those with extensive colitis.

Mortality in ulcerative colitis.

The pattern of mortality has been examined in a series of 676 patients with ulcerative colitis under long-term review to identify excesses or deficits in mortality for all causes of death in relation to the general population. The mortality risk for the whole series was 1.7 times that of the general population (p less than 0.001). Most of the excess mortality could be attributed to diseases of the digestive system. There was a heavy burden of mortality during the first year afer diagnosis and the first year after radical surgery. The significance of the excess of cancer deaths was due to the inclusion of patients who were diagnosed with cancer at first referral. In man there was a deficit of circulatory system deaths particularly those with early onset ulcerative colitis treated by panproctocolectomy after 40 yr of age. Mortality from all other causes including breast cancer showed no significant difference from that expected in the general population.

Cancer morbidity in ulcerative colitis.

Cancer morbidity at all sites has been studied in a series of 676 patients with ulcerative colitis under long-term review, of whom more than two-thirds had extensive disease, and the level and pattern of risk over time examined. Age-, sex-, and site-specific incidence rates were used to compute the number of cancers that might have been expected to occur. A highly significant excess of cancers was observed overall but the excess was due entirely to cancers of the digestive system. In women there was no excess or deficit of cancers outside the digestive system. In men there was a small deficit of cancers of the respiratory system. An overall 11-fold excess colorectal cancer risk was found in the series compared with that in a relevant general population after patient-years at risk had been corrected for surgical resection and patients with colorectal cancer at their first referral had been corrected for surgical resection and patients with colorectal cancer at their first referral had been excluded. When these data were expressed in an actuarial form the cumulative probability of developing colorectal cancer in the series was 8% (3.5-13%) at 25 years, after the diagnosis of ulcerative colitis had been established. The relative risk of developing colorectal cancer was highest in those patients developing colitis before the age of 30 years, and the relative risk fell as the age at diagnosis of their colitis increased. The pattern of risk of colorectal cancer over time suggests that there is an association between cancer and colitis in susceptible individuals and that the level of risk is related to age at onset of colitis.

Adenocarcinoma of the small intestine complicating Crohn's disease.

Adenocarcinoma of the small intestine is an uncommon complication of Crohn's disease. We report the clinical and pathological details of three cases diagnosed between 1968 and 1980 with a review of 58 cases from the literature. Of the 61 cases, 41 tumours occurred in the ileum, 18 in the jejunum, one in the duodenum and ileum, and one in the ileum and colon. Eighteen occurred in bypassed intestinal loops. The prognosis was poor: 44 patients (72%) had died with a mean interval of only 7.9 months from the diagnosis of cancer.

Mortality in Crohn's disease.

A series of 513 patients with Crohn's disease, who were followed for 1 to more than 35 yr by one unit, experienced a twofold increased risk of dying compared with a matched group drawn from the general population (102 observed; 51.8 expected; p < 0.001). The overall risk was similar for men and women and was greatest in the younger patients within a few years of diagnosis. The relative risk of dying decreased as the age at diagnosis of their Crohn's disease increased and also fell as the period of time from diagnosis increased. There was a small but significant excess of death from tumors of the digestive organs (9 observed; 4 expected; p < 0.05). There was also a significant excess of deaths from suicide in women (3 observed; 0.4 expected; p < 0.01). The major burden of mortality lay in causes directly attributable to Crohn's disease or to associated complications within the digestive system (46 observed; 1.41 expected; p < 0.001).

Malignancy in Crohn's disease.

Cancer morbidity has been evaluated in a series of 513 patients with Crohn's disease under long-term review between 1944-76. In comparison with morbidity rates for cancer in the West Midlands Region (the geographical area from which these patients were drawn) the 31 tumours that occurred represented a relative risk of 1.7 (P less than 0.01) of cancer at all sites. For tumours at sites within the digestive system the relative risk was 3.3 (P less than 0.001). A significant excess of tumours was found in both the upper (P less than 0.01) and lower (P less than 0.001) gastrointestinal tract. There was no excess of tumours at any site outside the digestive system.