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Biomedical subjects

G Griffioen

Publications and source records attributed to G Griffioen.

125 records · Page 7Linked to original sources

Flow cytometric detection of aneuploidy in colorectal adenomas.

Flow cytometry has been used to study the incidence of aneuploidy in a series of 55 colorectal adenomas (29 tubular adenomas, 22 tubulovillous adenomas, and 4 villous adenomas). For comparison, 5 nonadenomatous polyps, 4 normal mucosa samples from colectomy specimens and 16 colorectal cancers were measured. Fifteen (27%) adenomas were aneuploid, 33 (63%) were diploid, and 7 (11%) were peridiploid. The aneuploidy incidence increased with the size of the adenomas (less than 1 cm, 0%; 1 to 2 cm, 30%; greater than 2 cm, 50% aneuploid cases, respectively) but was less dependent on the histological type or degree of dysplasia. However, the degree of aneuploidy [mean DNA index of aneuploid stem lines] was significantly higher in tubulovillous adenomas [1.26 +/- 0.33 (SD)] than in tubular adenomas [1.09 +/- 0.04] and only slightly lower than in carcinomas [1.59 +/- 0.26]. The progressive increase in ploidy abnormality with size and histological type strongly supports the evidence for the adenoma-carcinoma sequence in the development of colorectal cancer.

Adenoma↗

Quantitative changes in adenosine deaminase isoenzymes in human colorectal adenocarcinomas.

Several reports have suggested that a decrease or absence of adenosine deaminase complexing protein (ADCP) is consistently associated with cancer. However, in other studies, decreased as well as increased ADCP levels were found. In the present study, we investigated ADCP levels in 37 colorectal adenocarcinomas and correlated the results with clinicopathological characteristics in individual carcinomas. The levels of adenosine deaminase (EC 3.5.4.4) and soluble ADCP were determined in tissue samples by, respectively, a spectrophotometric assay and an ADCP specific radioimmunoassay. The values in the individual tumors were compared with their histological characteristics, such as degree of differentiation, nuclear grading, and the preoperative plasma carcinoembryonic antigen levels in the patients. It was found that ADCP was decreased in about a third of the tumors but unaltered or even increased in others. However, there was an overall 40% increase of the adenosine deaminase activity in the tumors compared to normal tissue. There seems to be no simple correlation between any of the clinicopathological parameters and the ADCP or adenosine deaminase levels. Methods detecting ADCP at single cell level might be helpful in exploring its potential use as a cancer-associated marker.

Adenocarcinoma↗

Technetium-99m nanocolloid for the scintigraphic assessment of inflammatory bowel disease in the colon: its value in comparison with indium-111-labelled granulocytes.

The usefulness of 99mTc-nanocolloid for the assessment of localization and disease activity of colitis in patients suffering from inflammatory bowel disease (IBD) was investigated in 10 patients. Results of 99mTc-nanocolloid scintigraphy were compared with Indium-111 autologous granulocyte scintigraphy and the activity index according to Van Hees. In none of the patients a true positive result of the 99mTc-nanocolloid scintigraphy was encountered, while 111In-granulocyte scintigraphy was positive in 7 of 10 patients with active disease. Radioactivity became visible in the small bowel starting 2 h after injection of 99mTc-nanocolloid most likely because of excretion by the liver of degradation products of the radiopharmaceutical. The authors conclude that despite a previous communication 99mTc-nanocolloid cannot replace 111In-granulocytes for the assessment of IBD patients with active colitis.

Adult↗

Prognostic value of plasminogen activators and their inhibitors in colorectal cancer.

Colorectal tumorigenesis is associated with remarkable changes in the plasminogen activation system at the tissue level. The sequence of normal mucosa-adenomatous polyp-adenocarcinoma-metastasis is accompanied by an increase in the urokinase-type of plasminogen activator, the urokinase receptor and the inhibitors type-1 and type-2, with a concurrent decrease in the tissue-type plasminogen activator. Overall survival analysis of colorectal cancer patients, with a follow-up of more than 5 years, revealed that several of these components, in both the carcinomas and their corresponding normal mucosa, are of prognostic value independent of major clinicopathological parameters. Therefore, the plasminogen activation cascade not only contributes to the invasive and metastatic growth of colorectal tumours, but might also have a clinical impact with respect to adjuvant and intervention therapy.

Biomarkers, Tumor↗

Hereditary nonpolyposis colorectal cancer: results of long-term surveillance in 50 families.

A surveillance programme comprising either colonoscopy of sigmoidoscopy plus barium enema every 2-3 years was instituted in 50 hereditary nonpolyposis colorectal cancer (HNPCC) families. The families included 238 patients with colorectal cancer (CRC) (mean age at diagnosis: 43.7 years; range: 16-86 years). These patients had 597 first-degree relatives of whom 493 could be traced and 388 (79%) accepted the invitation for screening. The control group were relatives (index patients) with symptomatic CRC. The average follow-up duration was 5 years (1-20 years). Screening led to the detection of adenomas in 33 patients and CRC in 11 patients. Pathological examination revealed 1 Dukes' A, 7 Dukes' B and 3 Dukes' C cancers. In contrast, among the control group 47% had advanced CRC (Dukes' C or distant metastases). The 5-year survival of the screen-detected cases was 87% versus 63% in the control group. Of the 11 CRC cases in the screening group, 4 were detected within 1-4 years after a negative colonic examination. A large proportion of the polyps found in the screening and control groups showed a villous growth pattern and/or a high degree of dysplasia. We conclude that periodic examination of HNPCC families allows the detection of cancer at an earlier stage than in patients not under surveillance. Because of the possibly more aggressive nature of polyps associated with HNPCC, we recommend a screening interval of 1-2 years.

Adenoma↗

Effect of oral zinc supplementation on metallothionein and superoxide dismutase concentrations in patients with inflammatory bowel disease.

Oxygen-derived free radicals may contribute to intestinal tissue damage in inflammatory bowel disease. The concentrations of metallothionein and superoxide dismutase, two copper and zinc containing proteins involved in the scavenging of free radicals; were previously found to be decreased in the intestinal mucosa of patients with this disorder. The plasma zinc concentration is often decreased also in these patients. Since zinc is reported to be an efficient inducer of metallothionein synthesis, and probably of superoxide dismutase, we evaluated the effect of oral zinc supplementation on metallothionein and superoxide dismutase levels in patients with inflammatory bowel disease. Fourteen patients with inactive to moderately active inflammatory bowel disease received oral zinc supplementation (300 mg zinc aspartate, equal to 60 mg elemental zinc per day) for 4 weeks in a placebo-controlled double-blind cross-over trial. The plasma zinc concentration of these patients was low at the start of the study (12.2 +/- 1.7 mumol/L, P < 0.05), when compared to that of 22 healthy controls (13.6 +/- 2.3 mumol/L), but increased (P < 0.05) towards the levels of controls during the supplementation period (13.3 +/- 2.5 mumol/L). The concentrations of metallothionein and superoxide dismutase in plasma and in erythrocytes did not change in relation to the supplementation. The metallothionein concentration in both inflamed and non-inflamed intestinal mucosa was slightly higher after zinc supplementation but the superoxide dismutase concentration in the tissue was not altered. The histological inflammation score of intestinal biopsies, plasma albumin levels, and the disease activity index of the patients did not change during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Limited influence of pouch function on quality of life after ileal pouch-anal anastomosis.

BACKGROUND/AIMS: Despite a high frequency of pouch function disorders, most patients are satisfied with the outcome of ileo-anal pouch surgery. Aims of this study were: 1) To assess the influence of pouch function on quality of life and, 2) to determine which aspects of pouch dysfunction affect quality of life the most. METHODOLOGY: Questionnaires, addressing current pouch function and quality of life (Rand-36, GIQLI), were sent to all (53) patients with intact ileo-anal pouches, operated on between 1987 and 1997 in our center. RESULTS: Thirty-six of 53 patients responded. Compared to reference data, Rand-36 scores for role-limitations based on a physical problem, vitality and general health perception were significantly diminished (P < 0.01). Physical and social functioning were normal. The GIQLI score was slightly decreased (111.7 vs. 125.8, P < 0.01). Overall pouch function did not correlate with the overall Rand-36 score, but correlated well with the overall GIQLI score (r = -0.47). Both quality of life scores were diminished mainly by the night-time stool frequency. CONCLUSIONS: 1) Quality of life after IPAA, as measured with validated questionnaires, is only slightly decreased; 2) the GIQLI questionnaire is more sensitive to pouch dysfunction than the Rand-36; 3) night-time stool frequency influences quality of life the most.

Adolescent↗

Screening of families predisposed to cancer development in The Netherlands.

Screening for hereditary tumours provides a basis for secondary prevention. In 1985, the Foundation for the Detection of Hereditary Tumours was established in The Netherlands to coordinate screening in families with hereditary tumours. In the initial period of four years a large number of families were collected. Registration started with families with the multiple endocrine neoplasia syndrome type 2 and familial adenomatous polyposis. Later, families with the familial dysplastic nevus syndrome, hereditary nonpolyposis colorectal cancer and the multiple endocrine neoplasia syndrome type 1 were also collected and inventoried, because expansion of the registry to include these syndromes was considered. As a general conclusion based on our studies, it may be said that screening of families with the multiple endocrine neoplasia syndrome type 2, familial adenomatous polyposis, familial dysplastic nevus syndrome, and hereditary nonpolyposis colorectal cancer leads to detection of these tumours in an earlier stage, which in turn may permit curative treatment and improvement of the prognosis and life expectancy. Screening of the MEN-1 syndrome may improve the prognosis by favouring appropriate management decisions. It is evident that a detailed family cancer history is extremely important as an indicator of a genetic basis and has implications for family screening and follow up. The doctor's task of ensuring that the necessary investigations are carried out is made easier by use of the facilities of the Foundation for the Detection of Hereditary Tumours. The registration system in particular has assured the continuation of periodic examination, because the specialist is kept informed at all times. The collection of data and the preparation of an inventory of the data of families with hereditary tumours on a national scale have contributed to both the understanding of these syndromes and the optimalization of the screening procedures. The study of hereditary tumours is important, because it can provide clues concerning carcinogenesis in general.

Adenomatous Polyposis Coli↗

Colorectal adenomas: clinical and morphological aspects. A review of 166 polyps from 124 Dutch patients.

In a series of 124 consecutive Dutch patients the clinical and morphological features of 166 endoscopically removed colorectal adenomatous polyps were reviewed. The most frequent clinical symptom was manifest blood loss with the stools (51%), but no specific adenoma symptom seemed to exist. Barium enema X-ray examination was done in 108 patients, whereas all patients were colonoscoped. The routinely performed barium examinations detected 71% of the polyps that were found during endoscopy, but not all X-ray examinations were air contrast barium enemas. A good correlation between the localization of the adenomas after both diagnostic modalities was found, indicating that more than 80% were located in the left part of the colon. Nineteen percent of the patients had had a metachronous (pre)neoplastic lesion removed from their large bowel previously, while 40% of the patients had a synchronous polypoid lesion at the moment of polypectomy. Sixty-two percent of the adenomas were tubular, whereas 38% were villous adenomas. There was a strong correlation between size and villous architecture (r = 0.38; p less than 0.001). The epithelial dysplasia was mild in 21%, moderate in 70% and severe in 9% of the adenomas. The degree of dysplasia correlated well with the villous type of mucosal growth (r = 0.24; p less than 0.005). These findings indicate that, 1) there are no colorectal adenoma specific symptoms, 2) to detect colorectal adenomas colonoscopy is the investigation of choice, 3) after the detection of a colorectal adenoma the whole colon should be investigated, 4) colorectal adenoma patients should be kept under surveillance, and 5) determination of the diameter and of the degree of epithelial cell dysplasia may be helpful in assessing the biological behavior of an adenomatous polyp.

Adenoma↗

Vitamin B12 malabsorption after irradiation for gynaecological tumours.

The serum vitamin B12 levels were determined in 44 asymptomatic patients at least one year after completion of pelvic irradiation for a gynaecological tumour. Ten patients (23%) were found to have decreased levels of serum vitamin B12, of which six (14%) were assumed to be caused by malabsorption due to radiation damage to the terminal ileum as no other reason for a lower vitamin B12 level could be detected. Neither the radiation dose or volume nor the manifestation of acute or late radiation side effects appeared to be correlated with the finding of decreased levels of vitamin B12. It is concluded that even in asymptomatic patients who received pelvic irradiation, serum vitamin B12 levels can serve as a marker for radiation enteropathy. It is advocated to check vitamin B12 levels prior to the radiation treatment as well as during the follow-up of these patients.

Adult↗

Sites and types of p53 mutations in an unselected series of colorectal cancers in The Netherlands.

An unselected series of colorectal adenocarcinomas together with their corresponding normal mucosa, derived from 24 Dutch patients, was investigated for the loss of a marker mapping close to the region of p53 on chromosome 17p and for mutations in exons 5, 6, 7 and 8 of the p53 gene. The observed loss of heterozygosity of the marker on chromosome 17p was 36% of the informative cases, while 58% of the tumors contained a mutation in p53. This might be an indication that the mutation in p53 precedes the loss involving p53 on the homologous chromosome. Four tumors showed the presence of two different missense mutations in the p53 gene; in one of them the mutations involved the first two nucleotides of one and the same codon, while in a second case they were found within the same exon. In the remaining two cases the assessment of their situation, cis or trans, was not feasible. Six of the 18 mutations observed during this study were base transversions, including 3 G- > T substitutions. The hotspot codons 248, 273 and 282, were found to be involved in a third of the mutations.

Adult↗