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Biomedical subjects

O Kronborg

Publications and source records attributed to O Kronborg.

At least 37 records · Page 2Linked to original sources
PubMed2001

Colonic screening and surveillance.

Screening for colorectal cancer has not obtained worldwide acceptance in spite of its proven survival benefit for average-risk persons and some high-risk groups. The incidence of and mortality from colorectal cancer are worrying in Europe as well as in the USA, Australia and Japan. The best evidence-based studies are those published on screening using faecal occult blood tests, endoscopic methods and different tumour markers having been evaluated to a lesser degree. Feasibility studies are necessary before massive screening can be undertaken because the results obtained from randomized studies may not be reproduced to a satisfactory degree in average- as well as high-risk populations. Primary prevention by dietary intervention and drugs has been studied in great detail, so far without any major breakthrough. This chapter will address different screening methods in populations with a varying risk of colorectal cancer, together with providing a short review of prevention and intervention strategies.

Age Distribution↗
PubMed2001

Collagen metabolites in the peripheral and splanchnic circulation of patients with Crohn disease.

BACKGROUND: Fragments of collagen arising during synthesis and breakdown have been suggested as markers of fibrous tissue remodelling in Crohn disease. We compared serum concentrations of the C-terminal propeptide of collagen I (PICP), the N-terminal propeptide of collagen III (PIIINP) and the C-terminal telopeptide of type I collagen (ICTP) in the splanchnic and systemic circulation in Crohn disease requiring segmental intestinal resection. METHOD: 15 consecutive patients undergoing surgery due to strictures or continuous inflammation. Male:female ratio was 6:9. Blood was drawn from a peripheral vein prior to surgery. Immediately before intestinal resection, additional samples were drawn from the antecubital vein and from a mesenteric vein draining the affected intestinal segment. PIIINP, PICP and ICTP were measured with radioimmunoassays. RESULTS: Pre-surgery S-ICTP (median 5.5 microg/L; range 3.2-17.2 microg/L) was significantly increased in peripheral blood compared with healthy controls (median 2.6 microg/L; range 0.6-5.7 microg/L), P < or = 0.05. By contrast, S-PICP (median 98 microg/L; range 62-137 microg/L) and S-PIIINP (median 2.5 microg/L; range 1.2-7.4 microg/L) were significantly lower than S-PICP (median 133 microg/L; range 66-284 microg/L) and S-PIIINP (median 3.4 microg/L; range 1.0-7.1 microg/L) in healthy controls, P < or = 0.05. During surgery. no difference in S-PICP and S-PIIINP was documented between peripheral blood and splanchnic blood. In contrast, S-ICTP was increased in splanchnic blood (median 6.2 microg/L; range 2.7-17.4) compared to peripheral blood (median 5.0 microg/L; range 3.1-13.4) (P=0.05). CONCLUSION: The present study provides further evidence that the altered intestinal collagen metabolism in Crohn disease is reflected in the local and systemic circulation.

Adult↗
PubMed2001

A new fecal calprotectin test for colorectal neoplasia. Clinical results and comparison with previous method.

BACKGROUND: Fecal calprotectin is elevated in patients with colorectal cancer (CRC). An improved method has been developed. The aim was to evaluate sensitivity and specificity for CRC with the new fecal calprotectin method and to compare the results with those of the original method. METHODS: The study comprised 453 subjects including symptomatic CRC patients and CRC high risk subjects with and without CRC. Complete colonoscopy was performed. Calprotectin was measured with an enzyme linked immunosorbent assay (ELISA) using small (50-100 mg) feces samples. RESULTS: Fecal calprotectin levels were significantly elevated in symptomatic CRC and in asymptomatic CRC detected in high risk subjects. Calprotectin levels were significantly decreased 3 months after cancer removal. A cut-off limit of 50 microg/g resulted in a sensitivity of 89% in CRC patients and 79% in high risk subjects, compared to 89% and 75%, respectively, with the original method, using 10 mg/l as cut-off limit. Specificity was improved with the new method to 68% and 91% at cut-off of 50 and 150 microg/g, compared to 66% and 88%, respectively. Negative predictive value (NPV) was 99% for cut-off of 50 microg/g in the high risk population. One stool sample was sufficient, but measurement of two spots in two stools increased sensitivity to 98% for symptomatic and 82% for asymptomatic CRC. CONCLUSION: The new simple method, using small samples of feces, had a higher diagnostic accuracy, suggesting that it should be preferred to the original one, in screening high risk groups for CRC.

Adult↗
PubMed2000

Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group.

BACKGROUND: Some epidemiological studies have suggested that high dietary intake of calcium and fibre reduces colorectal carcinogenesis. Available data are not sufficient to serve as a basis for firm dietary advice. We undertook a multicentre randomised trial to test the effect of diet supplementation with calcium and fibre on adenoma recurrence. METHODS: We randomly assigned 665 patients with a history of colorectal adenomas to three treatment groups, in a parallel design: calcium gluconolactate and carbonate (2 g elemental calcium daily), fibre (3.5 g ispaghula husk), or placebo. Participants had colonoscopy after 3 years of follow-up. The primary endpoint was adenoma recurrence. Analyses were by intention to treat. FINDINGS: 23 patients died, 15 were lost to follow-up, 45 refused repeat colonoscopy, and five developed severe contraindications to colonoscopy. Among the 552 participants who completed the follow-up examination, 94 stopped treatment early. At least one adenoma developed in 28 (15.9%) of 176 patients in the calcium group, 58 (29.3%) of 198 in the fibre group, and 36 (20.2%) of 178 in the placebo group. The adjusted odds ratio for recurrence was 0.66 (95% CI 0.38-1.17; p=0.16) for calcium treatment and 1.67 (1.01-2.76, p=0.042) for the fibre treatment. The odds ratio associated with the fibre treatment was significantly higher in participants with baseline dietary calcium intake above the median than in those with intake below the median (interaction test, p=0.028) INTERPRETATION: Supplementation with fibre as ispaghula husk may have adverse effects on colorectal adenoma recurrence, especially in patients with high dietary calcium intake. Calcium supplementation was associated with a modest but not significant reduction in the risk of adenoma recurrence.

Adenoma↗
PubMed2000

Screening for early colorectal cancer.

There is now solid evidence from randomized trials suggesting that it is possible to reduce mortality from colorectal cancer by 15% to 25% by screening with fecal occult blood tests (FOBTs). The major benefit results from detection of early cancer in average-risk persons above 50 years of age who have a positive test followed by colonoscopy. However, it has to be demonstrated that the same acceptability can be reached in the general population as that obtained in trials. Many countries must establish a screening organization in a limited area to learn how satisfactory quality assurance can be obtained before a country-wide screening program is set up. So far, screening has not resulted in a reduced incidence of colorectal cancer in true population studies despite removal of two to three times as many possible precursors compared to controls. Cost-effectiveness will probably be as good as that known from screening for breast cancer with mammography and better than that for cervical cancer. However, the calculations are based on the unhydrated Hemoccult-II test in randomized trials. More sensitive methods would be attractive, but none has yet been evaluated properly in average-risk persons. There is no general agreement how to screen high risk groups such as patients with previous colorectal adenomas and carcinomas, one or two first-degree relatives with colorectal neoplasia, or ulcerative colitis. Families with familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, however, are presented with firm guidelines. Genetic screening has been helpful in no more than these two small groups in the colorectal carcinoma universe.

Colonoscopy↗
PubMed2000

Colon polyps and cancer.

Several important studies on screening for colorectal neoplasia were published in 1998-99, including average-risk as well as high-risk groups, and different strategies such as endoscopy, fecal occult blood tests, and other more specific markers of neoplasia. Some of these studies included the use of interventions other than initial screening and polypectomy; a few dealt with diagnostic methods in symptomatic patients, and the new diagnostic tool of virtual colonoscopy was highlighted by several authors. Endoscopic treatment for large adenomas and early colorectal cancer has become more widespread, but clearly it has limitations. Current discussion of the topic of colorectal polyps and cancer is largely based on the concept of the adenoma-carcinoma sequence, which is thought to be the most probable pathogenesis for colorectal cancer.

Adenomatous Polyps↗
PubMed2000

A prospective multicenter evaluation of new fecal occult blood tests in patients undergoing colonoscopy.

OBJECTIVE: Guaiac-based fecal occult blood (FOB) tests, in particular, Hemoccult II (HO), are commonly used to detect colorectal neoplasia. Because the sensitivity and specificity of these tests are critical to cost-effective screening programs, we aimed to investigate the improved performance characteristics of new FOB tests for known colonic lesions. METHODS: Nine centers worldwide performed FOB testing with guaiac-based tests (Hemoccult II [HO] and Hemoccult II SENSA [SENSA]) and immunochemical tests (HemeSelect [HS] and FlexSure OBT [FS]) on 554 patients referred for colonoscopy for predetermined indications. A combination testing strategy consisting of SENSA followed by HS or FS (which was considered positive only when both tests were positive) was also evaluated. Results of FOB tests were compared to findings on colonoscopy. RESULTS: Cancers were identified in 2.9% of subjects, whereas adenomas > or =10 mm were found in 39 patients. Small adenomas, colitis, and other lesions were identified in 141 patients. The positivity rate of HO for adenomas > or =10 mm was less than for SENSA (20.5% vs 35.9%, p < 0.05), whereas the positivity rate of HO, SENSA, FS, HS, or the combination tests for cancers was not statistically different. The overall positivity rates were significantly greater for FS (15.9%, p = 0.0002) and significantly lower using the combination tests (SENSA/FS 6.0%, p = 0.01; SENSA/HS 6.2%, p = 0.02) compared to HO (9.4%). In this study population, the relative specificity (i.e., true-negative tests/true-negatives + false-positives in patients without adenomas > or =10 mm or cancers) of HO (93.9%; 95% CI, 91.7-96.1) was similar to that of SENSA (92.8%; 95% CI, 90.4-95.2) and HS (90.1%; 95% CI, 87.4-92.8), and greater than FS (88.0%; 95% CI, 85.1-90.9, p < 0.001). When considering adenomas > or =10 mm, cancers alone or cancers and adenomas combined, the combination test using SENSA/FS was associated with significantly fewer false-positive tests than any of the individual tests. CONCLUSIONS: Compared to single tests, the combination test with the highly sensitive SENSA and an immunochemical test had slightly reduced sensitivity but significantly fewer false-positive tests than any single test. These data raise the possibility that a combination test (i.e., highly sensitive guaiac plus immunochemical) could reduce the costs of screening for colon cancer, and suggest that further study of combination test strategies is warranted.

Adenocarcinoma↗
PubMed2000

Faecal calprotectin levels in a high risk population for colorectal neoplasia.

BACKGROUND: Faecal concentrations of the protein calprotectin have been found to be elevated in patients with colorectal neoplasia, suggesting that it might be used as a screening tool for colorectal cancer as well as adenomas. AIMS: To measure the sensitivity and specificity of faecal calprotectin for the detection of adenomas in high risk individuals undergoing colonoscopy. Also, to investigate between and within stool variability of calprotectin concentrations. SUBJECTS: A total of 814 patients planned for colonoscopy were included for the following indications: positive faecal occult blood test, 25; neoplasia surveillance, 605; newly detected polyp, 130; and family risk, 54. METHODS: Two faecal samples from each of two stools were analysed using the PhiCal ELISA test device (Nycomed Pharma AS). RESULTS: Adenoma patients had significantly higher calprotectin levels than normal subjects (median 9.1 (95% confidence interval 7.5-10.1) v 6.6 (5.6-7.4)mg/l). There was no significant decrease in calprotectin levels after polypectomy. Levels in cancer patients were significantly higher than those in all other subgroups (median 17.6 mg/l (11.5-31.0)). With a cut off limit of 10 mg/l, the sensitivity for cancer was 74% and for adenoma 43%. Corresponding specificity values were 64% for no cancer and 67% for no neoplasia (cancer+adenoma). Specificity varied from 71% for one stool sample to 63% for four samples. Stool variability was small, suggesting that two spots from one stool were as discriminative as two spots from each of two stools. CONCLUSIONS: The sensitivity and specificity of faecal calprotectin levels as a marker for colorectal adenoma and carcinoma justifies its use in high risk groups, but specificity is too low for screening of average risk persons. Lack of a decrease in levels after polypectomy may be due to a more widespread leucocyte migration into the intestinal lumen than that at the polyp site, and needs further investigation.

Adenoma↗
PubMed1999

Possible advantages and drawbacks of adding flexible sigmoidoscopy to hemoccult-II in screening for colorectal cancer. A randomized study.

BACKGROUND: Flexible sigmoidoscopy (FS) has been recommended as a screening method to reduce mortality from colorectal cancer (CRC). The present study evaluates the effect of adding FS to the fecal occult blood test Hemoccult-II (H-II) on diagnostic yield of colorectal neoplasia. METHODS: A total of 10,978 normal persons aged 50-75 years were invited to participate, 5495 persons being allocated at random to H-II and FS and 5483 to H-II alone. RESULTS: In spite of a lower compliance (40% versus 56%) for the combined procedure, the diagnostic yield of colorectal neoplasia was higher than for H-II alone (12 CRC versus 4 CRC, and 72 large adenomas versus 14). Within 24-62 months after screening there were fewer CRCs detected after H-II + FS than after H-II alone. The stage distribution was less favorable than in screen-detected cases. CONCLUSION: One FS may not be an optimal way of screening, but FS deserves to be evaluated in randomized population studies including repeated H-II tests in the control arm.

Aged↗
PubMed1999

Influence of follow-up on health-related quality of life after radical surgery for colorectal cancer.

BACKGROUND: The possible benefit for patients of follow-up examinations after curative surgery for colorectal cancer is at present not proven. The purpose of this study was to evaluate the influence of follow-up examinations on health-related quality of life and to assess the attitude of the patients to check-ups. METHODS: A total of 350 patients who had had curative surgery for colorectal cancer and who had been subsequently randomized to either frequent follow-up or virtually no follow-up completed the Nottingham Health Profile and a second questionnaire assessing their attitude to the follow-up visits. RESULTS: The patients who were receiving more frequent follow-up had greater confidence in the check-ups, but the improvement in the health-related quality of life was only marginally better than that of those receiving few follow-up visits. CONCLUSION: The relatively small benefit for health-related quality of life does not justify expensive frequent routine examinations after surgery for colorectal cancer. The Nottingham Health Profile proved to be a reliable instrument within this patient group.

Adult↗
PubMed1999

The expression of p53, Ki-67 and urokinase plasminogen activator receptor in colorectal adenomas with true invasion and pseudoinvasion.

The recognition of pseudoinvasion is important in the differential diagnosis of adenocarcinoma in patients with adenomas. This distinction might occasionally be difficult, particularly when the dysplasia is pronounced. The present study was undertaken in order to investigate whether the immunohistochemical expression of p53, Ki-67 and the urokinase plasminogen activator receptor (uPAR) was different in adenomas with true invasion and pseudoinvasion. We studied 26 formalin-fixed, paraffin-embedded tumor samples, consisting of 10 cases of adenomas with pseudoinvasion and 16 cases of adenocarcinomas in adenomas. In this series of selected histologically typical cases a constant moderate or strong reaction for uPAR was present at the invasive front in all of the 16 adenomas with adenocarcinoma, but only focally in one of 10 adenomas with pseudoinvasion. The reactions for p53 and Ki-67 showed only minor differences. In conclusion, the immunohistochemical reaction for uPAR seems to be a useful supplement in cases without typical histology or with severe dysplasia.

Adenocarcinoma↗
PubMed1999

Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair.

BACKGROUND: Despite intensive research into the molecular abnormalities associated with colorectal cancer (CRC), no diagnostic tests have emerged which usefully complement standard histopathological assessments. AIMS: To assess the feasibility of using immunohistochemistry to detect replication error (RER) positive CRCs and determine the incidence of RER positivity within distinct patient subgroups. METHODS: 502 CRCs were analysed for RER positivity (at least two markers affected) and/or expression of hMSH2 and hMLH1. RESULTS: There were 15/30 (50%) patients with metachronous CRCs, 16/51 (31%) with synchronous CRCs, 14/45 (31%) with a proximal colon carcinoma, and 4/23 (17%) who developed a CRC under the age of 50 showed RER positivity. However, 0/54 patients who developed a solitary carcinoma of the rectum/left colon over the age of 50 showed RER positivity. Immunohistochemical analysis revealed that 66/66 (100%) RER positive carcinomas were associated with complete lack of expression of either hMSH2 or hMLH1. This correlation was confirmed using a further 101 proximal colon carcinomas. Patients with a mismatch repair defective carcinoma showed improved survival but a 5.54 times relative risk of developing a metachronous CRC. A prospective immunohistochemical study revealed 13/117 (11%) patients had a mismatch repair defective carcinoma. A fivefold excess of hMLH1 defective cases was noted. CONCLUSIONS: All RER positive carcinomas were identified by the immunohistochemical test. This is the first simple laboratory test which can be performed routinely on all CRCs. It will provide a method for selecting patients who should be investigated for HNPCC, offered long term follow up, and who may not respond to standard chemotherapy regimens.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Clinical evidence for the adenoma-carcinoma sequence.

A review is given on evidence supporting or rejecting the hypothesis of a colorectal adenoma-carcinoma sequence. The majority of studies discuss adenomas from a clinical point of view, but pathology has also been considered in detail, and molecular biology has been touched on. It is concluded the adenoma stage is, most probably, a phase on the way to carcinoma. But it remains to be shown what effect the removal of adenomas will have in the long run on the incidence of colorectal carcinoma.

Adenocarcinoma↗