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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.

Therapy of Digestive Disorders . Edited by Wolfe MM, Cohen S, Davis GL, et al . (Pp 881; hardback; illustrated; £85.) Philadelphia: WB Saunders, 1999. ISBN 0 72167 340 6. This is a substantial book edited by Dr Michael Wolfe with six of his colleagues acting as section editors. Many of the hundred or so contributors are members of the Boston home team. The others are from the key centres in North America with a smattering of contributors from Canada, Europe, Israel, and South America. This is in effect a GI textbook, but stripped largely of pathogenesis, pathophysiology, diagnosis, and differential diagnosis. Five …

The risk of developing colorectal cancer has been compared in two identically selected cohorts of patients with extensive Crohn's colitis (n = 125) and extensive ulcerative colitis (n = 486). In both groups the effects of selection bias have been reduced wherever possible. There was an 18-fold increase in the risk of developing colorectal cancer in extensive Crohn's colitis and a 19-fold increase in risk in extensive ulcerative colitis when compared with the general population, matched for age, sex, and years at risk. The absolute cumulative frequency of risk for developing colorectal cancer in extensive colitis was 8% at 22 years from onset of symptoms in the Crohn's disease group and 7% at 20 years from onset in the ulcerative colitis group. The relative risk of colorectal cancer was increased in both ulcerative colitis and Crohn's disease among those patients whose colitis started before the age of 25 years. Whether the absolute risk is greater in the younger age group or merely reflects that the expected number of carcinomas increases with age is uncertain. While there is an increased risk of developing colorectal cancer in extensive colitis the number of patients with Crohn's disease who actually develop colorectal cancer is small because many patients with extensive Crohn's colitis undergo colectomy early in the course of their disease to relieve persistent symptoms unresponsive to medical treatment.

The colorectal cancer risk in Crohn's disease eliminating all known biases was assessed in a cohort of 281 patients with Crohn's disease who resided in the West Midlands at the time of diagnosis, and were first seen within five years of onset of symptoms between 1945-1975. All patients were 15 years of age or more at onset and were followed up from 12-35 years (total 5213 person years at risk (PYR)). The colorectal cancer risk in the series compared with the risk in the general population was computed by applying sex and age specific PYRs to the date of death or end of the study period 31 December 1991. There were six colonic and two rectal cancers. Six of the eight colorectal cancers were diagnosed 20 or more years after the onset of Crohn's disease. The relative risk (RR) of colorectal cancer for the series as a whole was 3.4 (p < 0.001), with a fivefold excess in the colon, but no significant excess in the rectum. Patients with extensive colitis showed an 18-fold increase in risk (RR = 18.2, p < 0.001), which decreased with increasing age at onset. This study shows that there is a statistical excess risk of developing colorectal cancer in patients who develop their Crohn's disease at a young age of onset (less than 30 years of age).

Two men with longstanding ulcerative colitis who were treated with sulphasalazine for several years and who developed chronic renal failure are reported. Renal biopsy specimens showed histological changes consistent with drug induced chronic intestinal nephritis. Extensive investigation made other causes of chronic renal failure unlikely. One of these patients underwent renal transplantation, the other has impaired but stable renal function.

The ability of normal and Crohn's disease neutrophils to kill Candida albicans has been studied using neutrophils isolated from peripheral blood and suspended in phosphate buffered saline at 5 x 10(6) cells per ml. C albicans was grown to a stationary phase in broth culture and suspended in phosphate buffered saline at 10(7) organisms/ml. Neutrophils and Candida were then incubated together at 37 degrees C in a shaking water bath in the presence of fresh serum. At 30 and 60 minutes samples were withdrawn, neutrophils lysed, and Candida survival assessed by colony counting. Results were compared with control suspensions of Candida incubated with serum alone. After 30 and 60 minutes in the presence of autologous serum normal neutrophils had killed significantly more Candida than Crohn's disease neutrophils (mean (SD) 61.0 (16.7)% v 40.5 (16.2)% at 30 minutes, p less than 0.0001; 83.2 (7)% v 70.8) 16)% at 60 minutes, p less than 0.005). The results did not alter significantly when normal neutrophils were incubated with Candida in the presence of Crohn's disease serum instead of normal serum. When Crohn's disease neutrophils were incubated with Candida in the presence of normal serum instead of autologous serum there was some improvement in candidacidal ability at 30 minutes (48.9 (20.6)% v 40.5 (16.2)%, p less than 0.03) but not at 60 minutes. Phagocytosis, measured using a radiometric assay, was normal. Neutrophils from patients with Crohn's disease have an impaired ability to kill this granuloma provoking organism. It is not due to serum inhibitors or defective phagocytosis.

Summary Methods for hydrolyzing and solvolyzing conjugated bile acid sulfates were compared on reference mixtures of conjugated and unconjugated bile acid SUIfates using gas-liquid chromatography to assess recovery, and thin-layer chromatography and zonal scanning to define the products occurring after hydrolysis. Conventional methods in which solvolysis preceded vigorous alkaline saponification gave incomplete recoveries. However, essentially complete recovery of primary and secondary bile acid sulfates was obtained with a mild alkaline saponification procedure followed by acidification and extraction into ether, in which complete solvolysis was shown to occur within 12 hours. Based on these findings, we developed and validated a simple hydrolysis-solvolysis procedure; the method features mild alkaline hydrolysis, acidification to pH 1, and extraction with ether followed by a I-hour incubation.

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.

The hypothesis that abnormal fibronectin metabolism in Crohn's disease could be an important mechanism leading to stricture formation or postoperative infection was tested in three related studies. (1) Lower concentrations of plasma fibronectin (p less than 0.05) were found in 20 patients with small and large bowel Crohn's disease (mean 0.24 g/l) compared with 13 patients with more limited disease confined to only small or only large bowel (mean 0.27 g/l) or 20 healthy controls (mean 0.29 g/l). (2) In 25 patients followed for 10 days after operation for Crohn's disease, there was a significant fall in fibronectin concentrations of 43% (p less than 0.01, Wilcoxon's rank-sum test). This fall was maximal on the second postoperative day and was more marked in patients undergoing more major operative procedures. (3) The predictive value of plasma fibronectin for subsequent stricture formation or progression was studied for one year; during which 10 patients developed strictures requiring operative treatment. Higher plasma fibronectin concentrations were related to stricture formation, although there was not a complete, predictive relationship. In this study we found that plasma fibronectin concentrations were low in patients with extensive or severe Crohn's disease, fall after operation and may be related to the risk of stricture formation. This relationship is unlikely to be of clinical value, although it shows the potential significance of fibronectin in the pathogenesis of strictures.

We report the outcome of 63 consecutive patients with Crohn9s colitis treated by colectomy and ileorectal anastomosis between 1951-1981. There were no operative deaths. Serious postoperative complications occurred in 10 patients. The mean follow up since colectomy was 9.5 years. At 10 years the cumulative reoperation rate was 48% and the cumulative recurrence rate (based upon operative, radiological, and sigmoidoscopic evidence) was 64%. Ten patients have died during follow up. Two-thirds of the patients still under review have an intact ileorectal anastomosis. These results show that colectomy and ileorectal anastomosis is a useful operation in young patients with chronic ill health, diarrhoea, and anaemia in whom there is minimal anorectal disease. For suitable patients, the operation avoids the morbidity of a permanent stoma, pelvic dissection, and rectal excision. Recurrence developing in the ileum proximal to the anastomosis can often be resected and intestinal continuity preserved, whereas anorectal recurrence usually requires proctectomy.

One hundred and sixty two consecutive patients attending a clinic for inflammatory bowel disease (91 Crohn's, 71 ulcerative colitis) were assessed for the presence of anxiety and depression using a simple self-rating questionnaire (HAD scale) and a detailed evaluation (DSM-III). The overall prevalence of psychiatric illness (DSM-III) in ulcerative colitis and Crohn's disease was 34% and 33% respectively. There was no statistically significant association in ulcerative colitis patients between the presence of psychiatric illness and the present physical illness. Psychiatric illness was more common in the physically ill patients with Crohn's disease, compared with those who were well: 50% v 8% (p less than 0.01), using (HAD) criteria 66% v 37% (p less than 0.001). The presence of patients between the presence of psychiatric illness and the presence of physical illness. Psychiatric who were well: 50% v 8% (p less than 0.01) by DSM-III criteria, using (HAD) criteria 66% v 37% (p less than 0.001). The presence of psychiatric illness adversely affected physical recovery. Seventeen percent recovered when psychiatrically ill v 53% when psychiatrically well (p less than 0.025). The HAD scale was assessed as a screening method for psychiatric illness in this medical setting and had a sensitivity of 76% and a specificity of 79%.

The prevalence of use of oral contraception before the onset of disease was established in 100 consecutive women attending follow up clinics for inflammatory bowel disease. A significant excess of women with Crohn9s disease confined to the colon had taken oral contraceptives in the year before developing symptoms (10/16 (63%] compared with women with small-intestinal Crohn9s disease (12/49 (24%); p less than 0.02) and women with ulcerative colitis (3/35 (9%); p less than 0.0005). When the patient groups were matched for age and year of onset of disease usage of oral contraception before the onset of disease was still more common among women with isolated colonic Crohn9s disease (9/12, 75%) than among those with ulcerative colitis (2/12 (17%); p less than 0.02) and was also more common than would be expected from reported figures for oral contraception in England and Wales (31.4% of women aged under 41; p less than 0.005). A survey of current patient records showed that isolated colonic disease was at least twice as common among women with Crohn9s disease (63/218, 29%) compared with men (25/181, 14%; p less than 0.001). These data support the suggestion made previously that oral contraceptives may predispose to a colitis that resembles colonic Crohn9s disease.

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.

Summary We report a patient with ulcerative colitis who underwent colectomy when aged 25 years for multifocal high grade dysplasia which had developed within 2 years of diagnosis, and only 5 1/2 years after his first symptoms. The implications of this case for the management of ulcerative colitis are discussed.