Karen V. Winther

Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: A population‐based study from Copenhagen, Denmark

Background: It remains uncertain whether the increasing incidence of inflammatory bowel disease (IBD) during the last decades has been accompanied by an alteration in the presentation, course, and prognosis of the disease. To answer this question, 3 consecutive population‐based IBD cohorts from Copenhagen, Denmark (1962–2005), were assessed and evaluated. Methods: Phenotype, initial disease course, use of medications, cumulative surgery rate, standardized incidence ratio of colorectal cancer (CRC), and standardized mortality ratio (SMR) were compared in the 3 cohorts, which had a total of 641 patients with Crohns disease (CD) and 1575 patients with ulcerative colitis (UC). Results: From 1962 to 2005, the proportion of IBD patients suffering from CD increased (P < 0.001), time from onset of symptoms to diagnosis of CD decreased (P = 0.001), and median age at diagnosis of UC increased (P < 0.01). The prevalence of upper gastrointestinal involvement and pure colonic CD varied significantly between cohorts. UC patients diagnosed in the 1990s had a higher prevalence of proctitis, received more medications, and had a milder initial disease course than did previous patients. The surgery rate decreased significantly in CD but not in UC. The risk of CRC in IBD was close to expected over the entire period, whereas the mortality of patients with CD increased (overall SMR, 1.31; 95% CI, 1.07–1.60). Conclusions: Despite variations in the presentation and initial course of IBD during the last 5 decades, its long‐term prognosis remained fairly stable. Treatment of IBD changed recently, and future studies should address the effect of these changes on long‐term prognosis.

Long-term risk of cancer in ulcerative colitis: A population-based cohort study from Copenhagen County

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.

Intestinal and extra-intestinal cancer in Crohn's disease: follow-up of a population-based cohort in Copenhagen County, Denmark

Aim : To determine the long‐term risk of intestinal and extra‐intestinal malignancies in Crohns disease patients in Copenhagen County, Denmark.

Risk factors for colorectal neoplasia in inflammatory bowel disease: a nested case-control study from Copenhagen county, Denmark and Olmsted county, Minnesota.

OBJECTIVES:Population-based data on risk factors and protective factors for colorectal dysplasia and cancer in patients with inflammatory bowel disease (IBD) are sparse. We conducted a nested case–control study of such factors in two well-described IBD cohorts from Copenhagen County, Denmark and Olmsted County, Minnesota.METHODS:Forty-three neoplasia cases were matched on six criteria to 1–3 controls (N = 102). Medical records were scrutinized for demographic and clinical data. For each variable, the odds of neoplasia were estimated using conditional logistic regression.RESULTS:Primary sclerosing cholangitis (PSC) (odds ratio [OR] 6.9, 95% confidence interval [CI] 1.2–40), percentage of disease course with clinically active disease (OR [per 5% increase] 1.2, 95% CI 0.996–1.4), and ≥1 yr of continuous symptoms (OR 3.2, 95% CI 1.2–8.6) were associated with neoplasia, whereas a borderline association with median number of small-bowel x-rays (OR 1.3, 95% CI 0.96–1.6) was observed. We did not observe a protective effect of frequency of physician visits (OR 1.4, 95% CI 0.96–2.0), number of colonoscopies (OR 1.4, 95% CI 1.0–2.1), cumulative dose of sulfasalazine (OR [per 1,000 g] 1.1, 95% CI 1.0–1.3) and mesalamine (OR [per 1,000 g] 1.3, 95% CI 0.9–1.9), or partial intestinal resections (OR 1.5, 95% CI 0.3–7.1).CONCLUSIONS:Subgroups of IBD patients—those with PSC, severe long-standing disease, and exposure to x-ray—were at greater risk of colorectal neoplasia. The protective effect of close follow-up, colonoscopy, and treatment with 5-aminosalicylates was questionable.

Chimioprévention du cancer colorectal dans les maladies inflammatoires intestinales chroniques. Quels sont les médicaments proposés

RésuméLes maladies inflammatoires intestinales sont associées à une augmentation du risque de développer un cancer colorectal (CCR). La durée et l’étendue de la maladie sont des facteurs de risque importants, de même que la présence d’une cholangite sclérosante primitive (CSP) et un diagnostic à une âge précoce. La chimioprévention du cancer vise à empêcher, arrêter ou renverser la phase d’initiation ou de progression des cellules néoplasiques vers le cancer. Un intérêt croissant a été accordé aux agents chimiopréventifs potentiels dans la CCR sporadique et associée à la colite. Plusieurs études ont montré qu’une prise régulière de 5-aminosalicylates peut apporter une certaine protection contre le développement de la CCR dans les MICI. Chez les patients porteurs de colite ulcéreuse ou de CSP, il a été démontré que l’acide ursodéoxycolique pouvait réduire le risque de CCR. L’acide folique ne semble pas protecteur contre le cancer.Cet article donne un résumé d’un grand nombre d’études de diverses provenances, épidémiologiques,in vivo etin vitro, qui ont étudié la question de la chémoprévention dans les MICI.SummaryInflammatory bowel disease (IBD) is associated with an increased risk of developing colorectal cancer (CRC). Both duration and extent of disease are important risk factors, as is the presence of primary sclerosing cholangitis (PSC) and early age at diagnosis. Chemoprevention of cancer aims to prevent, arrest or reverse the initiation phase or the progression of neoplastic cells to cancer. A growing interest in possible chemopreventive agents, in both sporadic and colitisassociated CRC has occurred. Several studies have indicated that regular intake of 5-aminosalicylates can provide some protection against the development of CRC in IBD. In patients with ulcerative colitis and PSC ursodeoxycolic acid has been shown to reduce the risk of CRC. Folic acid has not been proven cancer protective in IBD.The current review gives an overview of the evidence of a variety of sources including epidemiological, in vivo, and in vitro studies that have addressed the question of chemoprevention in IBD.

Ulcerative colitis in Copenhagen county, Denmark, 1962–1997: Survival and cause-specific mortality

Background and Aims: The course and prognosis of a strictly regional cohort of 1161 patients with ulcerative colitis (UC) diagnosed in Copenhagen County between 1962 and 1987 has previously been described. The cohort has now been reassessed after extending the follow-up period another ten years in order to describe survival and gender-, age-, and cause-specific mortality. Methods: Patients were traced in the Danish Central Person and Cause-of-Death Registers and followed until death, emigration or end of study. Expected survival and mortality in a genderand age-matched background population were calculated using 1995 figures obtained from the National Statistics Department and individually computed person-years at risk. Cumulative survival curves were constructed using the Kaplan Meier method and compared applying the Mantel-Haenszel test. Comparison of observed and expected numbers of deaths were presented as relative risk (RR) and tested using the t method. Results: By the end of 1997 the median follow-up time was 19 years (range 1-36 years). 265 deaths occurred during the study period compared with 249.3 expected (RR = 1.06, P = 0.32). Among women there were 117 deaths vs. 114.4 expected (RR = 1.02, NS) and among men 148 deaths vs. 134.9 expected (RR = 1.1, NS). Age-specific mortality did not differ from the background population except in males age group 65-74 years where 52 deaths were observed compared to 38.5 expected (RR = 1.35, P = 0.03). Cumulative survival from diagnosis and 36 years ahead showed no difference from that of the background population. 31 (11.7%) of the 265 deaths were due to complications to Uc. 9 deaths were attributed to colorectal cancer. Among women a significantly lower occurrence of deaths caused by all kinds of cancer was found: 16 vs. 35.3 expected (P < 0.0001), while in the same time suicide was 3.6 times more frequent (6 vs. 1.69, P < 0.001). Among both sexes we found a significantly increased mortality due to respiratory diseases: 20 vs. 10.0 (P = 0.0017), and 27 vs. 11.6 (P < 0.00001) respectively. Conclusion: Overall mortality in this cohort of 1161 patients with UC did not differ from that of the background population from I to 36 years after diagnosis. In neither females nor males did the observed cumulative survival deviate from the expected. In both sexes a higher proportion of deaths caused by respiratory diseases, but not by cancer, was found. In females significantly fewer cancer deaths of all kinds were found, opposite to a higher occurrence of suicide.