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O Kronborg

Publications and source records attributed to O Kronborg.

At least 55 records · Page 3Linked to original sources

Cytogenetic analysis of colorectal adenomas: karyotypic comparisons of synchronous tumors.

The phenotypic progression of colorectal tumors is driven by their step-by-step acquisition of genomic alterations. These pathogenetically important mutations are at the same time markers of tumor clonality. The aim of this study was to describe the clonal relation among synchronous colorectal adenomas. Twenty-four colorectal adenomas from 11 patients were subjected to chromosome banding analysis. Clonal chromosome abnormalities were found in 20 tumors. Recurrent structural rearrangements involved chromosomes 1, 13, 17, and 18. The most common numerical changes were gain of chromosomes 7, 13, 20, and 3 and loss of chromosome 18. Eight adenomas had subclones as evidence of clonal evolution. Similar clones in separate polyps were seen in tumors from 6 patients; these adenomas were always located in the same part of the large bowel. In 2 patients, both with one rectal adenoma and one adenoma in the colon, no karyotypic similarity between the lesions was found. Our findings indicate that whereas close, but macroscopically distinct, synchronous colorectal adenomas usually have a common pathway of progression, perhaps even the same clonal origin, large bowel adenomas at a considerable distance from one another exhibit karyotypic differences, indicating that they arise independently.

Adenoma↗

Flow cytometric investigation of immune-response-related surface molecules on human colorectal cancers.

Our purpose was to clarify whether human colorectal cancer cells are equipped to present tumour-associated-antigens to the immune system, and whether this ability correlates with lymphoid infiltration, the Dukes' stage and Jass classification. Enzymatically dissociated tumour cells from 70 different colorectal cancers were monitored by multiparameter flow cytometry. Gating on EP4+ cells, the expression of the surface molecules HLA class I, HLA class II, CD80 (B7-1), CD54 (ICAM-I) and CD58 (LFA-3) was evaluated. In 60 of 70 tumours, all tumour cells expressed HLA class I, in 10 tumours 15-96% of the tumour cells expressed HLA class I. In 1 tumour, all tumour cells expressed HLA class II, in 67 tumours some expressed HLA class II, in 2 tumours none expressed HLA class II. Expression of CD58 was heterogeneous, and there was no or only sparse expression of CD80 and CD54. Expression of the HLA class I molecules, but not the class II, was correlated with lymphoid infiltration and the Jass classification. Expression of these surface molecules was not correlated with the Dukes' stage. The tumour cells were generally equipped to present antigens to the effector arm of the immune system since HLA class I is expressed, but the tumour cells were not optimal in stimulating an immune response, since HLA class II and CD58 were only marginally expressed and CD80 and CD54 were absent.

Adult↗

[Clinics for counseling on cancer genetics. Experiences with genetic studies and counseling on familial breast cancer and colorectal cancer].

Five to ten percent of cases of breast cancer and colorectal cancer are familial. These families can be divided into high-risk families and moderate-risk families. Cancer in high-risk families can often be explained by dominant inheritance of a gene causing increased susceptibility to cancer. There is a great demand for genetic counseling in these families, and the structure of and experiences from a familial cancer clinic at Odense University Hospital is described. The establishment of a familial cancer clinic involves three steps: 1) Identification of families with increased cancer susceptibility; 2) Molecular tests to identify gene carriers; 3) Clinical examinations for early detection of tumors. Achievement of these three steps requires the involvement of several medical specialties to ensure patient care. Experience with familial cancer clinics is still limited and the involvement of genetic testing and clinical examination programs at risk individuals are insufficiently examined. The rapidly improving techniques for genetic testing make it urgent that it is implemented as part of already established clinical programs.

Adult↗

Allelic imbalance and cytogenetic deletion of 1p in colorectal adenomas: a target region identified between DIS199 and DIS234.

Both cytogenetic and molecular genetic analyses have shown that many colorectal adenomas carry an acquired deletion distally in the short arm of one chromosome 1, but the two methods have never been brought to bear on the same tumors. The major part of this study was the analysis of 53 previously short-term cultured and karyotyped colorectal adenomas for allelic imbalance at eight microsatellite loci in 1p. Allelic imbalances were detected in seven of the 12 adenomas that had cytogenetically visible abnormalities of chromosome 1, as well as in four adenomas that either had a normal karyotype (one case) or had clonal chromosome abnormalities that did not seem to involve chromosome 1 (three cases); i.e., 30% of the adenomas had abnormalities involving 1p by the combined approach. A minimal region of overlap seemed to map to between DIS199 and DIS234, suggesting that this is a relevant target region. This genomic area contains the human homologue of the tumor modifier gene Mom1 (1p35-36.1), which, in mice, modifies the number of intestinal tumors in multiple intestinal neoplasia (Min)-mutated animals. To evaluate whether the imbalances corresponded to interstitial deletions of 1p material, we performed fluorescence in situ hybridization with a pericentromeric probe (15 adenomas) and a telomeric probe (6 adenomas) on uncultured cells from the 16 adenomas with chromosome 1 abnormalities. Except for three adenomas that had already been shown by banding analysis to have a trisomic pattern, two centromere 1 signals were invariably found. In the cases hybridized with the 1p-telomeric probe, we found the same frequencies of telomeric and centromeric signals, in agreement with the interpretation that the deletions were interstitial. One of the 53 adenomas had genomic instability, seen as new alleles at five of eight microsatellite loci. A comparison of the genetic findings with clinicopathologic data indicated that adenomas in the rectum have 1p abnormalities more often than do adenomas of the sigmoid colon, and that adenomas with 1p changes are larger than adenomas without abnormalities of chromosome 1.

Adenoma↗

Colorectal cancer screening: efficiency and effectiveness.

The cost-effectiveness of a series of mutually exclusive colorectal cancer screening programmes with varying screening interval and target group are analysed. Costs and effects for 60 possible screening programmes are simulated on the basis of data collected from a randomized trial initiated in 1985 in Funen County, Denmark. The screening test applied is the unhydrated Hemoccult-II. The analysis identifies six efficient programmes with cost-effectiveness estimates ranging from 17000 to 42500 Danish kroner (DKK) per life-year.

Aged↗

[Randomized population study of screening for intestinal cancer with Hemoccult-II].

The aim of the randomised study was to compare mortality rates from colorectal cancer (CRC) in persons screened with faecal occult-blood tests every two years during a 10-year period with those of unscreened similar controls. Thirty thousand nine hundred and sixty-seven persons aged 45-75 years in 1985 were allocated to screening and another 30,966 to a control group. Only participants who completed the first round with Hemoccult-II were invited for further screening. Participants with positive tests were offered colonoscopy. The primary endpoint was death from CRC. Sixty-seven percent completed the first screening round, and of these more than 90% accepted repeated screenings. During the 10 year study, 481 persons in the screening group had a diagnosis of CRC, compared with 483 unscreened controls. CRC mortality was significantly lower in the screening group (205 deaths) than in controls (249 deaths) (mortality ratio 0.82 [95% conf. lim. 0.68-0.99], p = 0.03). Our findings indicate that biennial screening by faecal occult-blood tests can reduce CRC mortality.

Adenoma↗

Cytogenetic findings in metastases from colorectal cancer.

Eighteen tumor samples from 11 patients with metastatic colorectal cancer were cytogenetically analyzed after short-term culturing. Of the 13 metastases examined, 11 were from lymph nodes, 1 from the peritoneum and 1 from the lung. In 5 of the 11 patients, matched samples from the primary tumor and lymph node metastases were analyzed. Cytogenetic similarities between the primary and secondary lesions were found in all 5 cases, indicating that many of the chromosomal aberrations presumably occurred before disease spreading took place. Compared with the primaries, the metastases appeared to exhibit decreased clonal heterogeneity but, concurrently, an increase in the karyotypic complexity of individual clones. Among the aberrations recurrently found in metastatic lesions were del(1)(p34), i(17)(q10), -18, -Y, -21, +7 and +20, all of which have been seen repeatedly in previous series of primary colorectal carcinomas, and del(10)(q22) and add(16)(p13), which so far have not been associated with primary tumors and which may play a particular pathogenetic role in the metastatic process.

Adenocarcinoma↗

[Emptying of colon prior to colonoscopy. A comparison between emptying using peroral polyethylene glycol-electrolyte and conventional emptying with dietary restrictions, laxatives and water lavage].

The purpose of the study was to compare the degree of bowel emptying at colonoscopy after preparation with either traditional water enema, dietary restrictions and laxatives or after oral lavage solution (Klean-Prep). Colonoscopy was performed in 104 patients over a two month period, 56 patients being allocated to the conventional preparation and 48 to Klean-Prep. The quality of bowel emptying was evaluated visually during endoscopy and by the proportion of incomplete colonoscopies. Bowel emptying was less satisfactory after Klean-Prep (p = 0.018) and seven incomplete colonoscopies resulted in contrast to two after conventional preparation. The results were obtained from a surgical department with a permanent small staff of motivated nurses preparing a huge number of patients for colonoscopy. No economic advantages could be demonstrated by the use of Klean-Prep.

Administration, Oral↗

The pattern of recurrent colorectal cancer in a prospective randomised study and the characteristics of diagnostic tests.

In a prospective randomised study, 597 patients subjected to curative surgery for colorectal cancer were allocated to either a group with frequent follow-up or a control group with follow-up every 5 years. The pattern of recurrence is reviewed. An equal number of recurrences was detected in the two groups, but the recurrence was diagnosed 9 months earlier in patients followed frequently, and the diagnostic characteristics of various tests dependent upon how often they were used. It is unlikely that frequent follow-up after curative surgery for colorectal cancer has a large positive influence upon survival, but a small benefit from an intensive follow-up program cannot be ruled out. The present results indicate that clinical examination, digital rectal examination, proctoscopy, colonoscopy and chest x-ray should be included in such a programme, whereas others (blood haemoglobin, faecal occult blood test, double contrast braium enema, serum alanine aminotransferase, and serum bilirubin) should be avoided, having a low sensitivity for detecting recurrent colorectal cancer.

Adult↗

Analysis of screening data: colorectal cancer.

BACKGROUND: This paper illustrates how data gathered from an existing screening programme against colorectal cancer can be used to produce new information on the natural history of colorectal cancer as well as the characteristics of the unhydrated Hemoccult II screening test. METHODS: A mathematical model is used, which on the basis of prevalence and interval incidence data from a randomized screening project initiated in Funen County, Denmark, estimates the sensitivity of the screening test and the sojourn time of the disease. RESULTS: The sensitivity of the Hemoccult is estimated at 62.1% and the mean sojourn time is estimated to be 2.1 years. CONCLUSIONS: The short sojourn time indicates that overall effectiveness of a Hemoccult II screening programme can be improved significantly by more frequent screening.

Aged↗

A prospective randomized study of follow-up after radical surgery for colorectal cancer.

BACKGROUND: The possible benefit for patients from follow-up examinations after curative surgery for colorectal cancer is unproven. The purpose of this study was to determine whether survival is improved by frequent follow-up examinations. METHODS: A total of 597 patients less than 76 years old treated with radical surgery for colorectal cancer were included in the study from 1983 to 1994. Patients were randomized to frequent follow-up (group 1) or virtually no follow-up (group 2) with examinations at 5 and 10 years. RESULTS: Group 1 comprised 290 patients, group 2 contained 307. Recurrence was equally frequent (26 per cent), but the time of diagnosis was 9 months earlier in group 1; also, more recurrences were asymptomatic in group 1 and more patients had new surgery with curative intent (P = 0.02). However, no improvement in overall survival or in cancer-related survival resulted. CONCLUSION: Patients subjected to intensive follow-up have recurrence diagnosed earlier, and have more operations for recurrence, but the survival results suggest that any major improvement by intensive follow-up is unlikely.

Adult↗

Chemoprevention of metachronous adenomas of the large bowel: design and interim results of a randomized trial of calcium and fibre. ECP Colon Group.

A European multicentric intervention study, led by the colon group of the European Cancer Prevention Organization, is under way. The main aim of the study is to test the efficacy of oral calcium supplementation with 2 g calcium per day and oral dietary supplementation with mucilaginous substances (as 3.8 g of ispaghula husk) on adenoma recurrence. Secondary aims are the study of treatment efficacy on colonic cell proliferation and on stool bile acid and sterol concentration. Serum and plasma samples are also collected. To better interpret the effect of the intervention, a diet history questionnaire and an aspirin and anti-inflammatory drug questionnaire are administered. The aim will be achieved through a randomized placebo-controlled clinical trial using a parallel design in patients aged 35 to 75 at entry with a complete colonoscopy and a clean colon. Overall, 655 subjects have been included. All randomized patients are followed up every six months for 3 years. If one of the evaluated interventions proves efficient, the benefits of a simple, safe and inexpensive prophylaxy for a very common cancer will be clear.

Adenoma↗