Widespread but not localized neoplasia in inflammatory bowel disease worsens the prognosis of colorectal cancer.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). Recently, new phenotypes of CRC in IBD have been suggested. Studies of the prognosis of CRC in IBD have shown conflicting results. The aim of the study was to analyze factors for prognosis in CRC-IBD, including the impact of the new phenotypes. METHODS: By using the nationwide, population-based Cancer Registry of Norway, we compared survival of a CRC-IBD cohort with CRC in the background population (all-CRC), adjusting for the topographical distribution of dysplasia at cancer diagnosis (widespread versus localized neoplasia in IBD) and other factors. We also analyzed prognostic factors within CRC-IBD. RESULTS: The mean age at CRC diagnosis was 43 years in widespread, 52 years in localized neoplasia IBD, and 70 years in all-CRC (P < 0.05). Adjusted for cofactors, prognosis of CRC-IBD was poorer compared to all-CRC (mortality rate ratio [MRR] 3.71, 95% confidence interval [CI]: 2.54-5.42, P < 0.001). Prognosis of widespread neoplasia IBD was poorer compared to all-CRC (MRR 4.27, 95% CI: 2.83-6.44, P < 0.001) and compared to localized neoplasia IBD (MRR 3.58, 95% CI: 0.87-14.72, P = 0.076). Survival was not significantly different between localized neoplasia IBD and all-CRC (P = 0.132). CONCLUSIONS: The results demonstrate lower age and poorer survival of CRC in IBD compared to CRC in the background population. The unfavorable effect of IBD on prognosis of CRC was pronounced in widespread neoplasia IBD. The diagnosis of this phenotype seems to be an important prognostic sign in patients with CRC in IBD.

[Measurement of calprotectin in faeces]. / Måling av kalprotektin i feces.

BACKGROUND: Calprotectin is a calcium-binding protein found in neutrophils. Increased levels are found in stools after mucosal damage due to inflammation, which causes influx of neutrophils into the gut lumen. MATERIAL AND METHOD: This article is based on a review of the most pertinent publications found on Medline and our clinical experience from more than 10 years of using the test. RESULTS: Calprotectin is primarily a marker of intestinal inflammation. The test is therefore a useful tool for investigation of abdominal discomfort. At diagnosis all patients with inflammatory bowel disease will have clearly elevated values of faecal calprotectin. On the other hand, in patients with irritable bowel syndrome the levels are normal. Normalization of faecal calprotectin seems to be a strong indicator of mucosal healing. INTERPRETATION: Correct use of the test can therefore contribute to reducing the number of unnecessary colonoscopies, which is especially important in children. Faecal calprotectin is a simple test and an objective parameter of inflammatory disease activity which is useful for assessment of disease course and monitoring of response to medical treatment in patients with inflammatory bowel disease.

Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study).

OBJECTIVE: Cohort studies of unselected and newly diagnosed patients are essential for a better understanding of the prognosis in ulcerative colitis (UC). The aim of this study was to evaluate the course of UC in a population-based inception cohort during the first 10 years, and to identify prognostic risk factors based on information gathered at diagnosis. MATERIAL AND METHODS: From 1990 to 1994, a population-based cohort of 843 patients with inflammatory bowel disease was enrolled in South-Eastern Norway. The cohort was systematically followed-up at 1, 5 and 10 years after diagnosis. RESULTS: Of 519 patients with UC, 423 completed the 10-year follow-up, 53 died and 43 were lost to follow-up. The mortality risk was not increased compared with that in the general population. The cumulative colectomy rate after 10 years was 9.8% (95% CI: 7.4-12.4%). Initial presentation with extensive colitis and erythrocyte sedimentation rate (ESR) > or =30 mm/h was associated with an increased hazard ratio (HR) (3.57, 95% CI: 1.60-7.96) and age > or =50 years at diagnosis, with reduced HR (0.28, 95% CI: 0.12-0.65) for subsequent colectomy. Relapsing disease was noted in 83%, but half (48%) of the patients were relapse free during the last 5 years. One-fifth (69/288) of patients with proctitis or left-sided colitis had progressed to extensive colitis. CONCLUSIONS: The prognosis for UC during the first 10 years was generally good. The colectomy rate was low, and a large proportion of patients were in remission as time progressed. Patients with initially extensive colitis and elevated ESR could benefit from an early potent medical treatment strategy.

Relationship between clinical parameters and the colitis-colorectal cancer interval in a cohort of patients with colorectal cancer in inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC), but more knowledge is needed about the possible relationship between clinical parameters and the time to development of cancer in IBD. The aim of the study was to determine the variability of the colitis-CRC interval and to analyze the association with clinical variables in an attempt to gain information on predictive factors of time to cancer within a relatively large cohort of CRC patients. MATERIAL AND METHODS: Patients diagnosed with IBD prior to 1 May 2005 at three university hospitals in Oslo were matched against the CRC files at the Cancer Registry of Norway. Only histological re-confirmed IBD and adenocarcinoma of the colorectum were included. RESULTS: Sixty-one patients with CRC in ulcerative colitis and 6 in Crohn's disease, including 13 CRC in primary sclerosing cholangitis (PSC), covering a follow-up of 1625 patient years,were identified. The median time from diagnosis of IBD to CRC was 17 years. Seven of 58 patients (12%) developed CRC within 10 years from onset of IBD symptoms and 14/67 (21%) within 10 years after the diagnosis of IBD. The colitis-CRC interval decreased by a factor of 0.154 (p = 0.018) when age at onset of IBD increased by one year. Mean age at onset of IBD was 30 years in patients with Dukes' stage C or D compared with 20 years in Dukes' stage A or B patients (p = 0.017). The colitis-CRC interval decreased by a factor of 0.138 (p = 0.003) when the percentage of the colitis-CRC interval with active symptoms increased by 1%. Patients with PSC were significantly younger at onset of IBD symptoms (PSC: 19 years versus no PSC:29 years, p = 0.04), but the colitis-CRC interval was similar to IBD without PSC (17 years versus 20 years, p = 0.236). Mean duration of the colitis-CRC interval was not related to family history or drug consumption prior to CRC. CONCLUSIONS: In the present cohort, for whom the median time from diagnosis of IBD to CRC was 17 years, 21% of the cancers developed before 10 years of disease, which is before colonoscopic screening is usually recommended. High age at onset of IBD may be related to a more aggressive development of CRC in IBD and early inclusion in screening programs might be considered for this group of patients. Symptom activity but not the diagnosis of PSC, family history of CRC or IBD or drug treatment seems to have an effect on the colitis-CRC interval.

Two distinct groups of colorectal cancer in inflammatory bowel disease.

BACKGROUND: The histological variability in colitis-associated colorectal cancer (CRC in inflammatory bowel disease [IBD]) and the association to clinical factors is unknown. METHODS: In population-based material including 67 patients with CRC in IBD, histopathology of the cancers and tissue samples from different colorectal localizations were reevaluated, and relationships to clinical factors analyzed. RESULTS: Forty-three of 60 patients (75%) showed dysplasia in the colorectum apart from the cancer, while 17 (25%) had no dysplasia at cancer diagnosis. Mean age at onset of IBD was 22 years in patients with and 34 years in patients without dysplasia (P = 0.01). The mean duration of colitis-CRC interval was 21 years in patients with and 16 years in patients without dysplasia (P = 0.02). The latter group included all patients with a colitis-CRC interval <10 years. Active inflammation was more likely to occur in patients with dysplasia (odds ratio [OR] 4.2). The 2 groups were not discriminated by gender, family history of CRC or IBD, diagnosis of PSC, medical treatment, active symptoms, or histological features like type of cancer and differentiation. In multiple logistic regression analysis the age at onset of IBD was the strongest predictive variable for dysplasia at cancer diagnosis (P = 0.025). CONCLUSIONS: Widespread neoplasia occurs in the majority of cases with CRC in IBD and is associated with early onset of IBD. Localized neoplasia occurs in about a quarter of the patients and shows an association with late-onset IBD. The 2 groups probably represent different pathogenetic entities of neoplasia in IBD. This might have consequences for surveillance strategies.

Clinical course in Crohn's disease: results of a five-year population-based follow-up study (the IBSEN study).

BACKGROUND: There are few population-based, prospective studies on the clinical course in patients with Crohn's disease (CD). AIM: To extend the observation period in a population-based prospective study (the IBSEN study) to find out more about the initial 5-year clinical course in CD patients and to relate the findings to the Vienna classification. METHODS: All patients diagnosed with inflammatory bowel disease (IBD) in southeastern Norway in the 4 years 1990-1993 were followed prospectively. The patients were invited to a systematic follow-up visit at their local hospital 1 and 5 years after inclusion in the study. The visits included a structured interview, a clinical examination and colonoscopy. RESULTS: Out of 843 patients initially diagnosed with IBD, 200 patients with definite CD were alive and had sufficient data for analysis 5 years after diagnosis. Changes in disease localization and behaviour in relation to the Vienna classification were observed in 27 (13.5%) and 35 patients (17.5%), respectively. During the observation period, 56 patients (28%) underwent surgery with intestinal resection, and half of these had disease localized in the terminal ileum. At the time of the 5-year visit, oral sulfasalazin and 5-aminosalicylic acid (5-ASA) were the most frequently used medications (by 54% of the patients), while oral glucocorticosteroids and azathioprine were being used by 25% and 13%, respectively. Seventy-two percent of the patients had taken oral glucocorticosteroids at some time in the course of the 5-year period. The majority of the patients had intestinal symptoms at 5 years, but only 16% had symptoms that interfered with everyday activities. Fourteen percent of the patients had had a relapse-free 5-year course; however, relapse was not related to the initial Vienna classification. When the patients described the clinical course, 44% reported an improvement in symptoms during the follow-up period. CONCLUSIONS: The 5-year clinical course in an unselected cohort of CD patients was mostly mild. The frequency of surgery was lower than that observed in other studies and only a minority of the patients had symptoms that interfered with everyday activities 5 years after the initial diagnosis. The Vienna classification predicted the risk of surgery, but did not predict symptoms at 5 years, relapses during the observation period or the course of disease as described by the patients.

Relationship between sick leave, unemployment, disability, and health-related quality of life in patients with inflammatory bowel disease.

BACKGROUND: The goal of this study was to determine the rate of work disability, unemployment, and sick leave in an unselected inflammatory bowel disease (IBD) cohort and to measure the effect of working status and disability on the patient's health-related quality of life (HRQOL). MATERIALS AND METHODS: All eligible patients were clinically examined and interviewed at the 5-year follow-up visit. In addition, they completed the 2 HRQOL questionnaires, the Short Form-36 Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire validated for use in Norway (N-IBDQ). Data regarding sick leave, unemployment, and disability pension (DP) also were collected. RESULTS: All together, 495 patients were or had been in the workforce during the 5-year follow-up period since diagnosis. Forty-two patients (8.5%) were on DP compared with 8.8% in the background population. Women with Crohn's disease (CD) had the highest probability of receiving DP (24.6%). A total of 58 patients (11.7%) reported they were unemployed at 5 years. This was equally distributed between men and women but was more frequent in patients with ulcerative colitis. Sick leave for all causes was reported in 47% with ulcerative colitis and 53% with CD, whereas IBD-related sick leave was reported in 18% and 23%, respectively. A majority (75%) had been sick <4 weeks, and a relatively small number of patients (25%) contributed to a large number of the total sick leave days. Both unemployment and DP reduced HRQOL scores, but the most pronounced effect on HRQOL was found in patients reporting IBD-related sick leave, measured with SF-36 and N-IBDQ. The observed differences also were highly clinically significant. Multiple regression analysis confirmed that IBD-related sick leave was the independent variable with the strongest association to the observed reduction in HRQOL scores. CONCLUSIONS: Unemployment or sick leave is more common in IBD patients than in the Norwegian background population. The number of patients receiving DP is significantly increased in women with CD but not in the other patient groups. Unemployment, sick leave, and DP are related to the patient's HRQOL in a negative way, but this effect is most pronounced in patients reporting IBD-related sick leave.

Course of disease, drug treatment and health-related quality of life in patients with inflammatory bowel disease 5 years after initial diagnosis.

OBJECTIVES: We assessed health-related quality of life (HRQOL) on the basis of a cross-sectional design in a population-based cohort of inflammatory bowel disease patients followed prospectively for 5 years after diagnosis. The aim was to investigate the influence of the course of disease, drug therapy, and relapse pattern on the patients' HRQOL. METHODS: All patients completed the validated Norwegian version of the Inflammatory Bowel Disease Questionnaire (N-IBDQ). We present data from 497 patients, 328 with ulcerative colitis and 169 with Crohn's disease. The mean age was 43.3 years, and 48% were female. RESULTS: Crohn's disease patients treated with systemic steroids or azathioprine had a statistically significant reduction in the N-IBDQ total score compared with non-users. Patients with a more severe disease pattern had a lower N-IBDQ total score. Patients reporting a relapse during the observation period had a significantly lower total score and dimension scores than patients without relapse in both diagnostic groups, and likewise there was a statistically significant decrease in N-IBDQ total score for those with extra-intestinal manifestations compared with those without. A multiple linear regression model showed that the number of relapses during the preceding year in ulcerative colitis, and sex (female gender) in Crohn's disease were the strongest predictor of a reduction in N-IBDQ total score. CONCLUSION: Treatment with systemic steroids or immunosuppressive drugs, a relapsing disease and the presence of extra-intestinal manifestations were associated with a clinically significant reduction in the patients' HRQOL.

Body composition in patients with inflammatory bowel disease: a population-based study.

OBJECTIVE: Weight loss and nutritional depletion are common features of inflammatory bowel disease. Our aim was to assess body composition in patients with Crohn's disease (CD) and ulcerative colitis (UC) and to evaluate possible differences between the patient groups and healthy subjects. METHODS: A total of 60 patients with CD, 60 patients with UC, and 60 healthy subjects were investigated. Each group consisted of 24 men and 36 women. Body composition was measured by dual x-ray absorptiometry and Z scores were obtained by comparison to age- and sex-matched normal values. RESULTS: Bone mineral content and lean body mass were significantly lower in patients with CD compared with patients with UC and healthy subjects. The body composition of CD men was more strongly affected than that of women. UC patients had significantly higher fat mass and body mass index than patients with CD and healthy subjects. There was no difference in the percentage of fat mass between the two patient groups. Corticosteroid treatment and smoking had a negative impact on bone mineral content and lean body mass in CD patients independently of each other. CONCLUSIONS: CD was associated with disturbances in body composition: both bone mineral content and lean body mass were significantly reduced, especially in men with CD. Corticosteroid therapy and smoking had a significant influence on body composition in patients with CD. When studying the effects of inflammatory bowel disease on body composition and nutritional status, patients with CD and UC should be evaluated separately.

Faecal calprotectin: a marker of inflammation throughout the intestinal tract.

Only a small proportion of patients with abdominal discomfort have organic disease, but a correct diagnosis can seldom be made by simple clinical examination. Additional diagnostic procedures must be employed, but these are expensive and demanding and carry a certain risk. Assessment of faecal concentrations of the neutrophil granulocyte-derived protein calprotectin can be used as a screening test--an 'ESR of the gut'--to select patients for further examination. The test can be performed on 1-2 g of random stool samples that can be sent to the laboratory by ordinary mail since the protein is remarkably stable in stools. The test has high sensitivities and specificities for gastrointestinal cancers and inflammatory bowel disease (IBD). Faecal calprotectin levels reflect the disease activity in IBD and can be used to monitor the response to treatment and detect relapses.