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Bob Dylan’s conversion to Christianity was a long time coming. So was his protest against protest, his hostility to politics. In this essay Dylan’s gospel songs are appreciated as the pivot of his songwriting, augmenting the multi-layered sense and multi-directed meaning in the invocatory design of his songs, a pattern which of course is also to be found both earlier and later in his oeuvre.

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. (Inflamm Bowel Dis 2010;)

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

There are few population-based, prospective studies on the clinical course in patients with Crohn's disease (CD).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.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.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.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.

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

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.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.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.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.

Health-related quality of life (HRQOL) has become an important tool in evaluating patient satisfaction in inflammatory bowel disease (IBD). So far, few prospective follow-up studies have been done to identify variables that influence HRQOL. We aimed to identify demographic and clinical variables that influence HRQOL 5 years after diagnosis in patients with ulcerative colitis (UC) or Crohn disease (CD) included in a prospective follow-up study from 1990 to 1994 (the IBSEN study).All patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific quality-of-life questionnaire translated into Norwegian and validated. We present data from 497 patients (328 UC patients and 169 CD patients, mean age 43.3 years, 48% female). The impact of age, gender, smoking, symptom severity, disease distribution, rheumatic symptoms and surgery on IBD patients' HRQOL was analysed.Women had a reduction in IBDQ total score of 10 points compared to men, CD patients had a reduction of 7.5 compared to UC patients. The patients with moderate/severe symptoms had a 50 points lower score than the patients without symptoms. The patients with rheumatic symptoms had a 10 points lower total score than the patients without these symptoms. All differences were statistically significant. The multiple regression analysis showed that symptom severity, rheumatic symptoms and female gender were the strongest predictors of reduction in HRQOL for both diagnosis groups.IBD symptoms, rheumatic symptoms and female gender have a significant influence on patients' HRQOL as measured by IBDQ. This was confirmed by the regression analysis.

(2004). Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease. Scandinavian Journal of Gastroenterology: Vol. 39, No. 10, pp. 1017-1020.

Objectives 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.

Although the pathogenesis of osteoporosis in inflammatory bowel disease (IBD) is not established, vitamin D deficiency and disturbances in calcium metabolism are thought to be of importance, especially in Crohn disease (CD). Vitamin D status is assessed and the relation between indices of calcium metabolism, including 25-hydroxyvitamin D and parathyroid hormone concentrations. and bone mineral density (BMD) in CD and ulcerative colitis (UC) are examined. Sixty patients with CD and 60 with UC were investigated. Each group comprised 24 men and 36 women.Vitamin D metabolites, parathyroid hormone and biochemical markers of bone metabolism were measured in blood and urine. Lumbar spine, femoral neck and total body BMD were measured by dual X-ray absorptiometry (DXA) and Z-scores were obtained by comparison with age- and sex-matched normal values.Vitamin D deficiency (25-hydroxyvitamin D330 nmol/l) was present in 27% of patients with CD and in 15% with UC. Furthermore, CD patients had a significantly lower mean concentration of 25-hydroxyvitamin D3 compared with UC patients. Vitamin D status was not related to BMD at any of the skeletal sites measured. Secondary hyperparathyroidism was found in 10 out of 27 patients with CD after small-bowel resections. No differences were found in serum osteocalcin and urine pyridinoline between patients with CD and those with UC.Hypovitaminosis D is common in CD patients. Patients with CD and small-bowel resections are at risk of developing secondary hyperparathyroidism and low BMD.

Purpose: To prospectively compare MR cholangiopancreaticography (MRCP) vs. endoscopic retrograde pancreaticography (ERCP) in patients with suspected common bile duct (CBD) stone disease. Material and Methods: Fifty consecutive patients with suspected CBD disease underwent MRCP and then ERCP within 12 h of each other. The result of the MRCP was blinded to the reader of the ERCP. The MRCP was done using a superconducting 1.0 T unit with a heavily T2-weighted breath-hold technique. The ERCP was done in the fluoroscopy suite by one of the clinicians and was evaluated by one of the radiologists who had not read the MRCP examinations. Results: There were 28 true-positives, 17 true-negatives, 1 false-positive, and 4 false-negatives. The sensitivity was 87.5% and the specificity 94.4%, respectively. The positive predictive value was 96.6% and the negative predictive value was 81.1%. Conclusion: MRCP was shown to be good enough to replace ERCP as a diagnostic method in patients with suspected CBD disease. MRCP is now our modality of choice after ultrasound in the diagnostic evaluation of these patients.

Background. Calprotectin is a calciumbinding protein found in neutrophils. Inflammatory damage of the intestinal mucosa causes an influx of neutrophils into the intestinal lumen, after which increased calprotectin levels can be measured in stools. This review is based on publications identified through a non-systematic search in Medline and our clinical experience from measuring calprotectin in faeces for more than 10 years. Results. Calprotectin is first of all a very good marker of intestinal inflammation. The test is therefore a useful tool for investigation of abdominal discomfort when symptoms and clinical examination make it difficult to determine whether the condition is organic or functional. At the time of diagnosis, all patients with inflammatory bowel disease have clearly increased levels of faecal calprotectin; in patients with irritable bowel syndrome the levels are normal. Normalization of faecal calprotectin seems to be a strong indicator of healing of the intestinal mucosa. Interpretation. Determination of calprotectin in faeces 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 treatment response and disease course in patients with inflammatory bowel disease. Calprotectin is a small protein that can be detected in various body fluids and tissues by using ELISA methodology and immunohistochemistry. The protein originates mainly from neutrophils. In the 1990s, detection of calprotectin in faeces was marketed as a test for colorectal cancer. The specificity of the test was too low, which was one of the reasons for the test never being accepted. Calprotectin has received a lot of attention during recent years, and only during the last year more than 50 articles have been published about calprotectin measurements in faeces or in other body fluids and tissues. The article discusses measurement of calprotectin in faeces in diagnostics and followup of patients with inflammatory bowel disease and irritable bowel syndrome. Material and method This review article is based on literature identified through a non-systematic search in Medline and own clinical experience with measuring calprotectin in faeces for more than 10 years. Calprotectin in faeces After granulocytes are released from bone marrow, they circulate freely in the blood. Thereafter they spend a few days in various peripheral tissues before they end their life in the gastrointestinal tract (1), where they release a number of antimicrobial substances (among them calprotectin). It is assumed that calprotectin has an important biological function in regulation of the intestinal microbiota. The intestinal mucosa is continuously

Since there are now several ways to treat symptomatic gallstone disease, one is able to select treatment on the basis of the patient's comfort, the practicability, effectiveness, and side effects of the technique, and the relative costs. In order to assess the present status of contact dissolution with methyl tert-butyl ether with regard to these aspects, the present enquiry reports the data of 21 European hospitals. Eight hundred three patients were selected for contact litholysis of cholesterol gallbladder stones using methyl tert-butyl ether. Percutaneous transhepatic puncture of the gallbladder was performed under x-ray or ultrasound guidance. Dissolution rate, side effects, and treatment times of 268 patients from one single center were compared to those of 535 patients from the other 20 centers. Two hundred sixty-four patients were followed for five years to assess stone recurrence. Physicians were asked how they assessed the expenditure of the method, the discomfort to the patients, and the staffing situation. Patients were asked to indicate their acceptance on an analog scale. Puncture was successful in 761 (94.8%) patients. Prophylactic administration of antibiotics was not necessary. Stones were dissolved in 724 (95.1%) patients. In 315 (43.5%) sludge remained in the gallbladder. The most severe complication was bile leakage, which led 12 (1.6%) patients to have elective cholecystectomy. Toxic injuries due to the ether were not reported. Method-related lethality amounted to 0%, 30-day-lethality to 0.4%. Stone recurrence rate was about 40% in solitary stones and about 70% in multiple stones over five years. Patients with multiple stones developed recurrent stones almost twice as often as those with solitary stones. The probability of stone recurrence in patients with sludge in the gallbladder after catheter removal was not statistically significantly different from those without sludge. Seventy to 90% of the centers found the puncture to be simple and not distressing for patients and the relation between expenditure and therapeutic success to be acceptable. The acceptance of contact litholysis by the patients was excellent. Contact litholysis when applied by an experienced team provides real advantages in the treatment of gallstone disease. The method is technically simple, well accepted by the patients, and can be easily applied in community hospitals. Contact litholysis may be of particular value in patients who are not suitable for anesthesia or surgery.

The relative frequencies of the autoimmune liver diseases primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) have not been studied. We therefore performed an epidemiologic investigation to describe the incidence and prevalence of the three diseases in a defined population.Patients with PBC, PSC, or AIH admitted to Aker University Hospital in Oslo were prospectively registered during the 10-year period 1986-95. This hospital serves a defined population of 130,000 inhabitants. The mean yearly incidence and the point prevalences at the end of each year were calculated.During the 10-year period 21 patients with PBC, 17 with PSC, and 25 with AIH were diagnosed. The mean annual incidence per 100,000 was 1.6 for PBC, 1.3 for PSC, and 1.9 for AIH. The point prevalences per 100,000 on 31 December 1995 were 14.6, 8.5, and 16.9 for PBC, PSC, and AIH, respectively.The prevalences of PBC and AIH are of the same order of magnitude and about twice as high as that of PSC. These epidemiologic data can be used to estimate the number of liver transplantations required due to autoimmune liver diseases.

BACKGROUND: The incidence figures for ulcerative colitis (UC) and Crohn's disease (CD) have been difficult to interpret, and geographical variations may be due to differences in classification criteria and study design. Few studies have based the incidence on prospective systematic follow up to confirm the initial diagnosis. METHODS: Between 1990 and 1993, in a prospective incidence study of inflammatory bowel disease (IBD) in south eastern Norway, 527 cases of UC, 228 cases of CD, 36 cases of indeterminate colitis (IND), and 55 cases of possible IBD were identified, yielding an annual incidence of 13.6, 5.9, 0.9, and 1.4 per 10(5) respectively. The diagnosis and all clinical data were reviewed by two gastroenterologists independently of each other. One to two years after diagnosis, all patients were offered a clinical follow up in which the initial diagnosis was assessed. RESULTS: Between the time of diagnosis and the follow up, 16 patients had died, four of complications related to IBD. Of the remaining 830 patients, 98% (814/830) were available for follow up, 93% (772/830) attended a clinical examination which included a colonoscopy in 77% (637/830), and the remainder had had a telephone interview, or reassessment based on hospital records, or both. Twenty seven patients were reclassified as not having IBD (3%), and 65 patients were characterised as possible IBD (8%). Of the patients initially classified as UC, 88% had their diagnosis confirmed, compared with 91% with an initial diagnosis of CD. In patients with indeterminate colitis, 33% were classified as definite UC and 17% as CD. This reclassification of patients yielded a corrected annual incidence of 12.8 for UC and 6.0 for CD. CONCLUSION: At follow up one to two years after the diagnosis of IBD, the initial incidence was only marginally altered. This is probably due to uniform inclusion criteria and careful diagnostic methods. The study also illustrates the importance of the re-evaluation of the initial diagnosis as close to 10%, both among patients with UC and CD, were reclassified at follow up.

This study comprised 62 outpatients with ulcerative colitis who underwent 64 colonoscopies. The disease activity was evaluated according to endoscopic and histological criteria. The results revealed a significant correlation between both the endoscopic as well as the histological gradings of disease activity and faecal calprotectin. The median faecal calprotectin levels in the control group (6 mg/l) and in the patients with no or low disease activity (11.5 mg/l) were significantly different (p < 0.0001). The median calprotectin level among patients with active disease was 68 mg/l which was significantly different from the latter group (p < 0.0001). Furthermore, we suggest that the degree of inflammation rather than the extent of the disease determined the faecal calprotectin levels. In conclusion, assessment of faecal calprotectin seems to be a marker of disease activity in patients with ulcerative colitis.

Background: Standardized criteria for Crohn's disease (CD) have only recently been developed, and prospective community-based incidence studies have been performed only during the past 3 decades. Geographic variations in incidence may therefore be due to differences in study design. Methods: From 1 January 1990 to 31 December 1993 all new cases of CD in four counties in southeastern Norway were prospectively registered. Results: A total of 225 new cases yielded an annual incidence of 5.8/105, with the highest incidence in mixed rural-urban areas. A peak of 11.2/105 in the annual incidence was found for the age group 15 to 24 years, with no significant differences in the overall annual incidence by gender. An average duration of 6 months of disease before diagnosis was unchanged during the 4 years. About half of the patients had isolated colonic disease, and one-quarter had isolated small-bowel disease. Conclusions: This study confirms the high incidence figures for Scandinavia, with a particularly high in...

Background: The incidence of ulcerative colitis (UC) has been difficult to interpret because prospective studies have only been performed during the past 3 decades. Geographic variations may therefore be due to differences in study design. Method: From 1 January 1990 to 31 December 1993 all new cases of UC in four counties in southeastern Norway were prospectively registered. Cases diagnosed as indeterminate colitis (IND) when endoscopy and histopathology were inconclusive or diverged with regard to diagnosis of UC or Crohn's disease (CD) were also included in the study. Results: A total of 525 cases of UC and 93 cases of IND yielded an mean annual incidence of 13.6/105 and 2.4/105, respectively. There were differences in incidence between counties, and a peak of 21.5/105 in the annual incidence was found for the age group 25 to 34 years in UC. The distribution was about equal for each of the groups proctitis and left-sided and extensive colitis. The time interval from onset of symptoms to diagnosis was 4...

To assess the feasibility of a prospective incidence study of inflammatory bowel disease (IBD), the registration methods and incidence figures during 1990 were evaluated. The study was a collaboration

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.

In the present study the prophylactic effect of concentrated wheat fibre on duodenal ulcer recurrence was evaluated. Eleven grams of fibre (Fiberform) or placebo was added to an ordinary Norwegian diet for 1 year after endoscopic healing of duodenal ulcer. The ulcer recurrence rates were 84% (31 of 37 patients) in the fibre-supplemented group and 85% (30 of 36 patients) in the placebo group (NS). The effect on ulcer symptoms was similar in both groups. Side effects were infrequently seen. A concentrated wheat fibre supplement seems to have no preventive effect when given to duodenal ulcer patients living on a traditional Norwegian diet.

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.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.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.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.

Several retrospective studies have reported seasonal variations in the relapse of ulcerative colitis, and two studies have found seasonality in the onset of ulcerative colitis, with a peak from August to January. This study was designed to investigate possible seasonal variations of onset of ulcerative colitis (UC) and Crohn's disease (CD). Patients with symptoms of one year or less were recruited from a prospective study of the incidence of inflammatory bowel disease, and the onset of symptoms was recorded month by month for four consecutive years. A total of 420 patients with UC and 142 patients with CD were included. There was monthly seasonality (p = 0.028) in symptomatic onset in December and January for UC but not for CD. It was found that environmental agents with known seasonality can be of importance for the seasonal variations of disease onset in UC.

Fecal calprotectin (CPT) is elevated in the majority of patients with known colorectal cancer (CRC), but the specificity is not clarified. Aim: To evaluate if a CPT test (PhiCal ELISA) was more sensitive than Hemoccult II test in detecting colorectal neoplasia, and to obtain reference values in subjects with normal colonoscopy. To evaluate a possible relation between number and extent of dysplasia of adenomas in first degree relatives of patients with CRC and the stage of the carcinoma in the index casus. Further to study the prevalence of CRC and adenomas in the first degree relatives of patients operated for CRC. Method: In a multicenter study, 253 first degree relatives of patients with CRC, aged 50–75 years (mean age 60 years) underwent colonoscopy after having delivered stool samples and three Hemoccult II slides. Results: In 237 first degree relatives from 148 patients with CRC, polyps were found in 118 (50%). Seventy three (31%) had adenomas and 17 had adenomas ≧10 mm. Five had asymptomatic cancers. The specificity of fecal CPT for adenomas at cut off levels ≤10, ≤15 and ≤20 mg/l were 47.4, 59.6 and 71.1%, respectively (max of three samples). The sensitivity at same cut off levels was 56.2, 45.2 and 31.5% and 4/5 of patients with carcinoma had CPT values >15 mg/l. The sensitivity of Hemoccult II for adenomas was 8%, and 4/5 of patients with carcinoma had negative Hemoccult II. The specificity for adenomas was 95%. Conclusion: Fecal CPT test was more sensitive than Hemoccult II in detecting colorectal neoplasia but the specificity was lower. In a high risk group like first degree relatives of patients with CRC, there are good reasons to consider fecal CPT as a first test in selecting patients for endoscopy.

We wanted to investigate the relationship between the fecal levels of granulocyte marker protein (GMP) and the presence of aberrant crypt foci (ACF) and colorectal cancer in rats given injections of azoxymethane (AOM) and fed either of two different diets, a basal diet plus 20% corn oil or 20% beef suet, respectively.The rats received intraperitoneal injections of AOM, 15 mg/kg, once weekly for 6 weeks and were killed after 22 weeks.In the group fed beef suet 17 of 19 rats developed colon cancer, whereas in the group fed corn oil 4 of 14 rats developed cancer. None of the 20 control rats fed either the beef suet or corn oil diets developed cancer or aberrant crypts, and GMP remained unchanged. Surprisingly, the numbers of ACF were significantly higher (467 versus 295; P = 0.004) in the group fed corn oil than in the group fed beef suet. On the other hand, the size (crypts/focus) of the ACF was significantly higher (P = 0.03) in the beef suet group. Furthermore, fecal GMP was significantly higher in the beef suet group than in the corn oil group after 18 weeks, and this difference increased further toward the end of the study. GMP was greatly increased in all rats with colorectal cancer.Fecal GMP may have provided us with a valuable tool for further studies of the induction and progression of neoplasia in rats and, possibly, in mice, since the anti-GMP antibody cross-reacts with feces extracts from mice.

Patients with inflammatory bowel disease (IBD) are at risk of developing metabolic bone disease. In diagnosing osteoporosis, bone mineral density (BMD) measurements play a key role. Our aims in this study were to assess the skeletal status with quantitative ultrasound (QUS) and to evaluate the ability of this method to predict BMD as measured by dual-energy X-ray absorptiometry (DXA) in IBD patients.Altogether 53 patients with Crohn disease (CD) and 57 with ulcerative colitis (UC) were studied by using a Lunar Achilles ultrasound bone densitometer. The ultrasound variables are broadband ultrasound attenuation (BUA) and speed of sound (SOS). The lumbar spine, femoral neck, and total body BMD were measured with DXA. The age- and sex-adjusted values (Z-scores) were obtained by comparison with age- and sex-matched normal values.In CD patients Z-scores for both BUA and SOS were significantly less than zero, and Z-score for SOS was significantly lower than that for UC patients. Z-scores for BMD measured with DXA were significantly lower at all measurements in patients with CD. QUS and DXA measurements were significantly correlated. However, the agreement between the measurements in each individual patient was poor. Body mass index (BMI) was a major determinant for both BUA and SOS. In CD patients low QUS variables were associated with corticosteroid therapy, and both CD and UC patients with previous fractures had low SOS values.Our study indicates that QUS and DXA are not interchangeable methods for estimation of bone status. QUS variables are insufficient to provide accurate prediction of BMD values and should therefore not be recommended as a screening test for osteoporosis in IBD patients.

PURPOSE: The study contained herein was undertaken to investigate fecal calprotectin excretion in a series of patients with colorectal carcinoma and to determine whether the excretion was influenced by localization or stage of the tumor. Furthermore, the effect of surgical treatment on the concentrations was studied. Fecal calprotectin was also compared with plasma concentrations of calprotectin, carcinoembryonic antigen, and C-reactive protein. METHODS: Fecal calprotectin was measured in 119 consecutive patients admitted for treatment of colorectal carcinoma. In 116 (97.5 percent) patients, resectional surgery was performed. Plasma calprotectin was measured in 90 (76 percent) patients, carcinoembryonic antigen in 88 (74 percent) patients, and C-reactive protein in 82 (69 percent) patients. RESULTS: Median fecal calprotectin concentration in the 119 patients was 50 (range, 2-950) mg/l, which was significantly (P

The clinical course and prognosis in ulcerative colitis (UC) and Crohn's disease (CD) have been described in many studies, mostly retrospective. Such studies are hampered by problems such as inclusion over a long time period, proper definitions, incomplete case records, and outdated methods of diagnosis. In a prospective study we identified 846 patients with inflammatory bowel disease (IBD) over a 4-year period from 1990 to 1993. Uniform diagnostic and therapeutic strategies were used as a basis for later assessment of the short-term clinical course in different subgroups of UC and CD and analysis of potential risk factors for relapse or surgery.At the time of follow-up, a mean of 16.2 months after diagnosis, 496 UC patients and 232 CD patients, altogether 98%, were available for evaluation. A colonoscopy was performed in 88% (410 of 465) of the UC patients attending a clinical examination and in 76% (164 of 216) of the CD patients.Eleven patients with UC and five patients with CD died during follow-up, four of complications related to IBD. The cumulative 1-year relapse rate in the remaining patients was 50% for UC and 47% for CD. Of the patients with relapses 11 % of the UC patients and 10% of the CD patients had a chronic relapsing course without any difference with regard to the various disease categories in UC or CD. An increased risk of relapse was found in patients less than 50 years old only in UC. In UC a higher risk for surgery was found in patients with extensive colitis compared with left-sided colitis (P = 0.011), and CD patients with small-bowel involvement had a higher risk of surgery than patients with disease confined to the colon (P = 0.021). There was no excess risk of relapse or surgery in smokers as compared with non-smokers or former smokers, nor did the risk of relapse vary with the level of cigarette consumption in either UC or CD patients.The high relapse rate of around 50% for both UC and CD calls for a review of the existing treatment. Further follow-up will be necessary to improve our ability to make clinical decisions relating to medical and surgical treatment options.

BACKGROUND: Patients with inflammatory bowel disease are at risk of developing metabolic bone disease. AIMS: To compare bone mineral density in patients with Crohn's disease with patients with ulcerative colitis and healthy subjects, and to evaluate possible risk factors for bone loss in inflammatory bowel disease. PATIENTS: 60 patients with Crohn's disease, 60 with ulcerative colitis, and 60 healthy subjects were investigated. Each group consisted of 24 men and 36 women. METHODS: Lumbar spine, femoral neck, and total body bone mineral density were measured by dual x ray absorptiometry (DXA), and Z scores were obtained by comparison with age and sex matched normal values. RESULTS: Mean Z scores were significantly lower in patients with Crohn's disease compared with patients with ulcerative colitis and healthy subjects. Patients with ulcerative colitis had bone mineral densities similar to healthy subjects. Use of corticosteroids, body mass index (BMI), and sex were significant predictor variables for bone mineral density in Crohn's disease. In ulcerative colitis only body mass index and sex were of significant importance. Disease localisation and small bowel resections had no influence on bone mineral density in patients with Crohn's disease. CONCLUSIONS: Patients with Crohn's disease have reduced bone mineral density. Several factors are probably involved, but the reduction is associated with corticosteroid therapy. When studying skeletal effects of inflammatory bowel disease, patients with Crohn's disease and those with ulcerative colitis should be evaluated separately.

Multifocal intestinal infarctions, due to thrombosis in small vessels, might be a pathogenetic mechanism for Crohn's disease (CD). Deficiency of free protein S may contribute to the development of such thrombotic occlusions. In the present study free protein S was measured in 54 patients with CD. In 31 patients (57.4%) the plasma concentrations of free protein S were below the lower normal range. The mean value of free protein S in CD patients was 72.2%, as compared with 97.5% in healthy subjects (p < 0.01). The concentrations of C4b-binding protein and protein C were similar in the two groups. Free protein S levels were not correlated to disease activity, previous surgery or complications, extraintestinal manifestations, or current medical therapy. The impairment of the protein S/protein C/thrombomodulin system found in patients with CD favours coagulation and might be of importance for both the development of CD and its thromboembolic complications.

Calprotectin, a prominent cytosol protein in neutrophil granulocytes, was present in increased concentrations in stools from 50 of 53 patients with colorectal cancer, 32 of 40 patients with colorectal polyps, and all of 18 patients with gastric cancer. After radical surgery, faecal calprotectin levels reverted to the normal range in all but one patient with colorectal cancer. Calprotectin determinations are simplified by the stability of this protein in stools. Reliable estimates can be obtained in samples of only 5 g. On the basis of data from the literature, the test for calprotectin seems better than that for occult blood for the detection of gastrointestinal neoplasms.

The safety and efficacy of methyl fert-butyl ether (MTBE) dissolution of cholesterol gallbladder stones were evaluated in 25 patients with increased risk for surgery. Two patients were treated twice. The MTBE was infused and aspirated manually through a percutaneous transhepatic catheter to the gallbladder. The placement of the catheter failed in three patients (11%). In 19 of 24 patients (79%) there was complete dissolution of stones after a mean treatment time of 12.2 h (range, 4.3-19.5 h). In five patients treatment was discontinued before complete dissolution owing to technical problems or side effects. Side effects were nausea, pain, vasovagal reaction, and fever. Fifteen patients were followed up for a mean of 15.7 months after dissolution. Stone recurrence was found in eight patients, five of whom suffered symptomatic relapse. We conclude that dissolution therapy with MTBE is a safe and adequate alternative to surgery in selected high-risk patients.

Free protein S, protein C, and C4b-binding protein (C4b-BP) were measured in randomly selected outpatients: 22 with Crohn's disease (CD) and 16 with ulcerative colitis (UC). Active disease was recorded in 10 patients with CD and 4 with UC. Fourteen patients (63.6%) with CD and 4 (25%) with UC had free protein S values below the normal range, with mean values of 62% and 78% of that found in healthy control subjects (p < 0.01). The C4b-BP level was 127% in patients with CD as compared with 89% in both healthy subjects and UC patients (p < 0.01). The protein C levels were similar in the three groups. The present results add to the factors already known favouring thromboembolic complications in inflammatory bowel disease and which might play a major role both for the pathogenesis and for the increased tendency to venous thromboembolism in these diseases.

This study describes methods for extraction and quantification of calprotectin (L1 protein) in feces by enzyme immunoassay. This protein is a prominent antimicrobial component of neutrophils, monocytes, macrophages, and squamous epithelia. Calprotectin was stable in feces during storage for 7 days at room temperature. Small fecal samples taken from a 24-h feces collection gave a reliable estimate of calprotectin. Within-assay precision was 1.9%, and between-assay precision 14.8%. In healthy subjects (n = 33) median fecal calprotectin was 2025 micrograms/l and in hospital controls (n = 40) 10,500 micrograms/l. Median values in patients with Crohn's disease (n = 21) was 43,000 micrograms/l and in ulcerative colitis (n = 17) 40,000 micrograms/l. Fecal calprotectin was significantly correlated to fecal alpha 1-antitrypsin in the patients with Crohn's disease. Ten of 11 patients with gastrointestinal carcinomas had calprotectin level above the suggested reference limit of 6740 micrograms/l.