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Background & aims: Ulcerative colitis (UC) is associated with an increased risk for colorectal cancer (CRC) and possibly also increased risk for cancers outside the intestinal tract. We followed-up a population-based cohort of 1160 patients with UC diagnosed in Copenhagen County between 1962 and 1987 for up to 36 years to analyze the overall and site-specific cancer risk. Methods: Observed vs. expected cancers were presented as standardized morbidity ratio (SMR) with 95% exact confidence intervals (CI) calculated by using individual person-years at risk and sex- and age-specific incidence rates for the Danish background population in 1995. Results: The cohort was followed-up for a median of 19 years, or 22,290 person-years. A total of 124 malignancies were observed compared with 139.85 expected (SMR, .89; 95% CI, .74-1.07). The observed number of CRCs was almost exactly equal to expected: 13 cases vs. 12.42 (SMR, 1.05; 95% CI, .56-1.79). The cumulative probability of CRC was .4% by 10 years, 1.1% by 20 years, and 2.1% by 30 years of disease. Among men, melanoma was increased (SMR, 3.45; 95% CI, 1.38-7.10); otherwise, no increased risk for cancer could be detected. No hepatobiliary cancers and no increased risk for lymphoma or leukemia were found. Conclusions: Neither the overall cancer risk, nor the CRC risk, were increased in this population-based cohort after a median of 19 years of follow-up evaluation. An active surgical approach in medical treatment failures and long-term use of 5-aminosalicylic acid (5-ASA) as relapse prevention may explain this remarkable result.

Background & Aims: A population-based cohort from Copenhagen County comprising 1160 patients diagnosed with ulcerative colitis between 1962 and 1987 was followed-up until 1997 to describe survival and cause-specific mortality. Methods: Observed vs. expected deaths were presented as standardized mortality ratio (SMR) with exact 95% confidence intervals (CI) calculated by using individually registered person-years at risk and Danish 1995 mortality rates. Cumulative survival curves were calculated. Results: A total of 261 deaths occurred, not significantly different from the expected number of 249 (SMR, 1.05; 95% CI, 0.92-1.19). The median age at death among men was 70 years (range, 6-96 years) and among women 74 years (range, 25-96 years). Twenty-five deaths (9.6%) were caused by complications to ulcerative colitis, mostly infectious and cardiovascular postoperative complications. Patients older than 50 years of age at diagnosis and with extensive colitis showed an increased mortality within the first 2 years because of ulcerative colitis-associated causes. The mortality from colorectal cancer was not increased and that of cancer in general was significantly lower than expected: 50 vs. 71 (SMR, 0.70; 95% CI, 0.52-0.93). A significantly increased mortality from pulmonary embolism and pneumonia was found. Among women only, death from genitourinary tract diseases and suicide was significantly increased. Conclusions: Despite an overall normal life expectancy for patients with ulcerative colitis, patients >50 years of age and with extensive colitis at diagnosis had increased mortality within the first 2 years after diagnosis, owing to colitis-associated postoperative complications and comorbidity.

Background: The prognosis of patients with ulcerative colitis (UC) has previously been described with regard to mortality, cancer occurrence, and need for colectomy on the basis of an annual follow-up of a regional cohort of UC patients in Copenhagen County diagnosed in 1962-87. The objective of this study was to examine the prognosis with regard to spread of disease and to evaluate possible prognostic factors with regard to spread of disease and colectomy by multivariate regression analysis. Methods: An inception cohort of 1161 patients with UC was examined by actuarial analysis and by multivariate regression analysis of a subgroup of 467 patients diagnosed in 1979-87. Results: The probability for further progression of proctosigmoiditis, evaluated by sigmoidoscopy and radiology, was 53% after 25 years. The probability for regression was 76.8% for substantial colitis and 75.7% for pancolitis after 25 years. Multivariate regression analysis showed that the occurrence of the symptoms abdominal pain and diarrhoea was prognostically unfavourable with regard to the progression from proctosigmoiditis. Age influenced the regression probability in extensive disease. With regard to colectomy the following variables influenced the prognosis: fever, general condition, serum albumin, mucopus in stools, and diarrhoea at onset. Conclusion: Disease extent in UC is not static but changes with time in approximately half of the patients. This finding should have implications for the follow-up. Ulcerative proctitis should be considered the same disease as UC and needs the same long-term follow-up.

Intercellular adhesion molecule (ICAM)-1 promotes the initial interaction between macrophages and T cells during immune activation. We have measured serum levels of soluble ICAM-1 (sICAM-1) by ELISA in 27 patients with ulcerative colitis (UC), 31 with Crohn's disease (CD), and 29 healthy subjects. The median sICAM-1 serum concentration was significantly increased in inflammatory bowel disease (IBD) patients (355 ng/ml, range 195–855) compared to controls (245 ng/ml, 155–580) (P=0.001). Variance analysis for trend showed that sICAM-1 levels were significantly higher in patients with active CD and UC, compared to those with inactive disease and controls (P=0.00002). The concentration of sICAM-1 was higher in CD patients (365 ng/ml 230–470) compared to UC (300 ng/ml 195–855) (P=0.01). Furthermore, weak but significant correlations were found between serum levels of sICAM-1 and: soluble IL-2 receptors, orosomucoid, and C-reactive protein. It is suggested that increased circulating sICAM-1 levels may reflect increased adhesiveness and signal transmission across cells, probably as a result of shedding of the parent molecule during local cellular immuneresponsesin vivo.

Background: The study was a follow-up of an inception cohort of 373 patients with Crohn's disease.Methods: Annual assessments, life table analyses, and Markov chain analyses, estimating the probability for remission and relapse with time, and working capacity were carried out.Results: The clinical course of Crohn's disease differs markedly over time, from ever-relapsing cases to a quiescent course with remission for several years, interrupted by years with relapse. No predictive factors have been found for the subsequent course with regard to age, sex, extent of disease at diagnosis, and treatment in the year of diagnosis. The relapse rate within the year of diagnosis and the following 2 years, however, does correlate positively (p = 0.00001) with the relapse rate in the following 5 years. Furthermore, the relapse rate for 1 year during the disease course influences the relapse rate the following year, indicating a disease pattern over time with waves of at least 2 years' duration. A slight tendency towards burning out was found. The disease course reflected in working capacity for the patients showed that a minor part - up to 15% after 15 years - will become incapable and obtain disablement pension, while 75% of the patients each year are fully capable of work. Within 10 years 50% of the patients will not have experienced any year with impaired capacity for work.

An epidemiologic study was performed 1) to estimate the occurrence of epithelioid granulomas in the appendix wall among patients in whom an appendectomy had been performed, 2) to identify patients with granulomas in the appendix who had symptoms and history compatible with Crohn's disease, and 3) to estimate the long-term prognosis. Within a 5-year period 6051 patients in Copenhagen County underwent appendectomy. Six patients (0.1%) had epithelioid granulomas of the appendix (0.2 per 105 inhabitants per year). Follow-up of the six patients for 9-11 years (median, 9.5 years) showed that all had been free of gastrointestinal symptoms since the operation. Among the 373 patients diagnosed as having Crohn's disease in Copenhagen County between 1962 and 1987, 3 patients had their disease initially confined to the appendix. Follow-up in these patients showed no recurrence within a median of 6 years (range, 4-7 years). Patients with epithelioid granulomas of the appendix have an excellent long-term prognosis, which could be explained by the fact that the condition seems to be unrelated to Crohn's disease.

The incidence of ulcerative colitis was estimated during the period 1962 to 1987 in the county of Copenhagen. Within this area of approximately 550,000 inhabitants, 1161 patients were diagnosed. The mean annual incidence for the period was 8.1 per 105 inhabitants. There were significant increases in incidence in the early 1970s and in the early 1980s, both of which were followed by significant decreases. A bimodal age distribution was found in men, with incidence peaks in young adult life and late in life. In women a peak incidence was found in the young adult age group. The interval from onset of symptoms to diagnosis in terms of years remained unchanged over the period, with a median of 1 year (range, 0-37 years). The extent of disease at diagnosis was total colon in 18% of the patients, a substantial part of the colon in 36%, and distal colon in 44% - with no changes during the study period. The distribution of different localizations did not differ among age groups except for a tendency towards more extensive disease in young patients, below 20 years of age. The disease activity in the 1st year was fulminant in 9.1% of the cases, moderate to high in 70.7%, and low in 20.2%, with a tendency towards higher activity in patients diagnosed late in the study period. The prevalence of ulcerative colitis increased steadily during the study period, reaching a value at the end of the study (31 December 1987) of 161 per 105 inhabitants.

Munkholm P, Langholz E, Nielsen OH, Kreiner S, Binder V. Incidence and prevalence of Crohn's disease in the county of Copenhagen, 1962-87: a sixfold increase in incidence. Scand J Gastroenterol 1992;27:609-614.The incidence of Crohn's disease increased sixfold from 1962 to 1987 in the county of Copenhagen. The mean annual incidence for 1979-87 was 4.1 per 105 inhabitants. The increase was found equally in both sexes, with an approximately 40% higher incidence in women. The maximal incidence was found in the 15- to 24-year age group, being 12.8 per 105 per year for women and 6.0 per 105 per year for men, as mean of the period 1979-87. The prevalence at the end of the study was 54 per 105 inhabitants, 46 per 105 in men and 63 per 105 in women. The clinical appearance of the disease at the time of diagnosis was remarkably similar during the study period with regard to both the localization of disease and the clinical symptoms and signs. A slightly higher percentage of the patients, however, were in high disease activity at diagnosis in the later years of the study.

Circulating human neutrophil granulocytes (PMNs) from patients with rheumatoid arthritis (RA) have earlier been described to possess an enhanced capacity for production of certain 5-lipoxygenase-derived metabolites of arachidonic acid (AA), 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4). In the present investigation the endogenous AA metabolism of synovial fluid PMNs of RA patients was studied and compared with that of the corresponding circulating PMNs. Synovial fluid PMNs prelabelled with 14C-AA released significantly less radioactivity than circulating PMNs when stimulated with calcium ionophore. Furthermore, synovial fluid PMNs produced significantly smaller amounts of both 5-HETE and LTB4 than circulating PMNs from the same patients, whereas no such difference was observed in the LTB4 catabolites or the cyclo-oxygenase products. More information dealing with the complex way in which arachidonic acid is metabolized in diseased RA joints may provide future rational approaches in the treatment of this chronic inflammatory disease.

Background and Methods: In a geographically derived incidence cohort diagnosed from 1962 to 1987 we identified all patients with onset of inflammatory bowel diseases (IBD) before the age of 15 years, to describe the clinical course and to compare the course and prognosis with those of adult-onset IBD. Results: The mean incidence of IBD among children below 15 years was 2.2/105, 2.0 for ulcerative colitis (UC) and 0.2 for Crohn's disease (CD). At diagnosis children with UC had more extensive disease than adults (P > 0.05). Abdominal pain was also more frequent. The cumulative colectomy probability was 6% after 1 year and 29% after 20 years, not different from that of adults. More females underwent colectomy. With regard to disease activity, apart from the year of diagnosis 60-70% of UC patients were in remission in each of the first 10 years of disease; for CD about 50% were in remission. One patient with UC developed carcinoma of the sigmoid colon. Time between onset of UC and development of carcinoma was 12 years. For CD no differences in clinical appearance at diagnosis and course between children and adults were found in relationship to surgery. No deaths occurred among CD patients. Three CD patients were severely growth-retarded already at diagnosis. Conclusion: The incidence of IBD is low in childhood. At diagnosis children with UC have more widespread disease than adults. Childhood-onset CD does not differ in clinical presentation, disease course, or prognosis from adult-onset CD. However, growth retardation is a problem among male CD patients.