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Biomedical subjects

F M Nagengast

Publications and source records attributed to F M Nagengast.

At least 37 records · Page 2Linked to original sources
PubMed2003

[From gene to disease; E-cadherin and hereditary diffuse gastric cancer].

Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant syndrome associated with an early-onset, histologically diffuse, signet ring cell type gastric cancer and the occurrence of cancer at other anatomical sites, i.e. breast, colon, prostate and ovary. Inactivating germline mutations in the CDH1 gene, encoding the cell to cell adhesion protein E-cadherin, predispose to HDGC. About 30% of HDGC families have a proven pathogenic CDH1 mutation. Lifetime penetrance of HDGC is about 70%. In HDGC families the recommendation for prophylactic total gastrectomy is restricted to carriers of an inactivating CDH1 mutation.

Cadherins↗
PubMed2003

Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens.

Gastrointestinal tumours are among the most common malignancies in Western society, the majority of which are associated with dietary and lifestyle factors. Many dietary or lifestyle factors have been identified which may have toxic or carcinogenic properties. However, several dietary compounds also able to reduce gastrointestinal cancer rates in both humans and animals have been characterized. Though the exact mechanism leading to the anticarcinogenic action of these compounds is not fully known, it has been demonstrated that this chemopreventive capacity may be due to elevation of the glutathione S-transferase detoxification enzymes. Here we have investigated the effect of several anticarcinogens on the gastrointestinal UDP-glucuronosyltransferase (UGT) enzymes. Diets of male Wistar rats were supplemented with ellagic acid, ferulic acid, Brussels sprouts, quercetin, alpha-angelicalactone, tannic acid, coumarin, fumaric acid, curcumin and flavone, separately, and combinations of alpha-angelicalactone and flavone. Hepatic and intestinal (proximal, mid and distal small intestine and colon) UGT enzyme activities were quantified using 4-nitrophenol and 4-methylumbelliferone as substrates. All anticarcinogens tested increased UGT enzyme activity with both substrates, at one at least of the five different sites investigated. alpha-Angelicalactone, coumarin and curcumin showed enhanced UGT enzyme activities at all five sites. Both small and large intestinal UGT enzyme activities were increased by quercetin, alpha-angelicalactone, coumarin, curcumin and flavone. Except for tannic acid, all agents induced hepatic UGT enzyme activity. Furthermore, dietary administration of alpha-angelicalactone and flavone, given individually or in combination, enhanced the UGT detoxification system in the liver and, to a lesser extent, in intestine. In conclusion, induction of gastrointestinal UGT enzyme activities after consumption of dietary anticarcinogens may contribute to a better detoxification of potentially carcinogenic compounds and subsequently to the prevention of gastrointestinal cancer.

Animals↗
PubMed2003

[A patient with biliary papillomatosis, a rare condition of the biliary system, with fatal outcome].

A 21-year-old man was admitted because of upper abdominal pain and cholestasis. Endoscopic retrograde cholangiopancreatography was suggestive of primary sclerosing cholangitis. During follow-up the patient developed symptoms which were not compatible with primary sclerosing cholangitis, i.e. icterus and weight loss. Finally the patient died, almost three years after presentation, because of a metastatic adenocarcinoma which had arisen from biliary papillomatosis. Biliary papillomatosis is characterised by papillary adenomatous proliferation of the bile duct epithelium. It has a high chance of malignant degeneration. The only curative option would have been transplantation of the liver and biliary system, but this ought to have happened at an early stage before malignant degeneration had occurred.

Adenocarcinoma↗
PubMed2003

[The treatment of gallstone disease in the elderly].

Gallstone diseases (asymptomatic, symptomatic and complicated) are frequently seen in the elderly; the prevalence increases proportionally with age. At higher ages (> 60 years) the presentation of symptomatic or complicated gallstone disease is frequently atypical. Complicated gallstone disease (especially cholecystitis and cholangitis) in the elderly is associated with high morbidity and mortality rates. The introduction of laparoscopic cholecystectomy has decreased the morbidity and mortality rates of symptomatic and complicated gallstone disease in the elderly; for elective procedures in particular, the risks hardly differ from those for younger patients. Percutaneous cholecystostomy is an effective and safe alternative for (laparoscopic) cholecystectomy in high-risk patients with an acute cholecystitis. Endoscopic retrograde cholangiopancreaticography (ERCP) with sphincterotomy is also the treatment of choice for common bile duct stones in the elderly. After removal of common bile duct stones (whether or not accompanied by cholangitis or pancreatitis) a laparoscopic cholecystectomy should be performed, unless contraindications are present.

Acute Disease↗
PubMed2003

Tissue levels of fish fatty acids and risk of colorectal adenomas: a case-control study (Netherlands).

Epidemiological and animal studies have suggested that a high ratio of n-3 fish fatty acids to arachidonic acid (AA), might protect against colorectal carcinogenesis. Competition of n-3 and n-6 fatty acids, especially AA, for the enzyme cyclooxygenase-2 may be responsible for this effect. To examine the relation between fish intake and colorectal adenomas, data from a Dutch case-control study were analysed. All 52 cases and 57 controls filled out a food questionnaire, underwent a full colonic examination and have had a fat biopsy from the buttock. Intake of fish and fish fatty acids was inversely associated with colorectal adenomas although not statistically significant. For the ratio of fish fatty acids to AA, the ORs in the second and third tertile were 1.2 and 0.8 (p-trend = 0.78). Tissue levels of fish fatty acids were inversely associated and tissue levels of AA were positively associated with adenomas, although not statistically significant. However, the OR for the ratio of fish fatty acids to AA was 0.2 in the second and third tertile (p-trend = 0.002). In line with the hypothesis, a high ratio of fish fatty acids to AA in adipose tissue was associated with a lower risk of colorectal adenomas.

Adenoma↗
PubMed2003

Very low incidence of microsatellite instability in rectal cancers from families at risk for HNPCC.

In families at risk for hereditary non-polyposis colorectal cancer (HNPCC) that do not fulfill all clinical criteria for HNPCC, additional evidence is sought by testing cancer specimens for microsatellite instability (MSI). We investigated whether the location of a colorectal cancer (CRC) predicts the result of MSI-testing in these families. One hundred and seven patients suspected for HNPCC were offered MSI-testing. MSI-testing was positive in 6/7 patients with endometrial carcinoma and in 22/100 patients with CRC. Only one out of 22 (4%) rectal cancers was MSI-positive, and in this patient no mismatch repair (MMR) gene mutation was found. Right-sided colon carcinomas were more likely to be MSI-positive (14/37 or 38%), followed by left-sided colon carcinomas (7/4 or 17%) (p < 0.05), with 6/14 and 4/7 MMR gene mutations, respectively. The likelihood that a tumor would be MSI-positive was 3.3 times greater for right-sided than for left-sided colon cancer (OR 3.3, p < 0.05). Microsatellite instability was 8.1 times more frequent in colon cancers than in rectal cancers (p < 0.05). The presence of MSI was independently related to fulfillment of the Bethesda criteria (OR 7.0, p = 0.01). In families with multiple cases of colorectal cancer, the rectal cancers are only rarely MSI-positive. This indicates that even in families with multiple colorectal cancers, rectal cancers are most commonly of sporadic origin.

Adult↗
PubMed2003

Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect.

BACKGROUND: In view of the high risk of developing a new primary colorectal carcinoma (CRC), subtotal colectomy rather than segmental resection or hemicolectomy is the preferred treatment in hereditary non-polyposis colorectal cancer (HNPCC) patients. Subtotal colectomy however implies a substantial decrease in quality of life. To date, colonoscopic surveillance has been shown to reduce CRC occurrence. AIMS: To compare the potential health effects in terms of life expectancy (LE) for patients undergoing subtotal colectomy or hemicolectomy for CRC. METHODS: A decision analysis (Markov) model was created. Information on the 10 year risk of CRC after subtotal colectomy (4%) and hemicolectomy (16%) and stages of CRCs detected within a two year surveillance interval (32% Dukes' A, 54% Dukes' B, and 14% Dukes' C) were derived from two cohort studies. Five year survival rates used for the different Dukes stages (A, B, and C) were 98%, 80%, and 60%, respectively. Remaining LE values were calculated for hypothetical cohorts with an age at CRC diagnosis of 27, 47, and 67 years, respectively. Remaining LE values were also calculated for patients with CRC of Dukes' stage A. RESULTS: The overall LE gain of subtotal colectomy compared with hemicolectomy at ages 27, 47, and 67 was 2.3, 1, and 0.3 years, respectively. Specifically for Dukes' stage A, this would be 3.4, 1.5, and 0.4 years. CONCLUSIONS: Unless surveillance results improve, subtotal colectomy still seems the preferred treatment for CRC in HNPCC in view of the difference in LE. For older patients, hemicolectomy may be an option as there is no appreciable difference in LE.

Adult↗
PubMed2002

Meat consumption and meat preparation in relation to colorectal adenomas among sporadic and HNPCC family patients in The Netherlands.

Meat consumption and meat preparation methods are thought to be associated with the risk of sporadic colorectal cancer, and possibly adenomas. As the same somatic mutations occur in sporadic adenomas and hereditary non-polyposis colorectal cancer (HNPCC)-related adenomas, similar exogenous factors may play a role in the development of both types of adenoma. In a case control study among 57 sporadic colorectal adenoma cases and 62 adenoma cases from HNPCC families (and 148 adenoma-free controls) from the Netherlands, we examined whether meat consumption and preparation are similarly associated with sporadic and suspected HNPCC colorectal adenomas. Frequency of meat consumption was not significantly associated with adenoma risk in our population of sporadic and HNPCC family cases and controls (Odds Ratios (OR) for high versus low consumption were 1.0 and 0.6, respectively). Interestingly, consumption of red meat and specific preparation methods (i.e., "not adding any water" and " closed lid with most meat types") slightly, but non-significantly, increased the risk of adenomas in the sporadic group only (OR, 95% Confidence Interval (CI): 4.1, 0.7-23.0, 2.0, 0.6-6.5 and 2.6, 0.9-7.2, respectively). This is the first study to examine possible differences or similarities in risk factors for sporadic and HNPCC colorectal carcinogenesis. Our results do not provide support for meat consumption as a risk factor for adenoma formation in HNPCC family members. Some characteristics of habitual meat preparation in the Netherlands may, however, increase the risk of sporadic adenomas.

Adenoma↗
PubMed2001

[Revised CBO guideline 'Follow-up after polypectomy'].

The purpose of follow-up after polypectomy of one or more colorectal adenomatous polyps, is the timely removal of new adenomas and thereby the prevention of colorectal cancer. The first check-up following index-polypectomy can be carried out after six years if one or two adenomas were encountered during the index polypectomy, and after three years if three or more adenomas were encountered. The same check-up interval of six and three years respectively applies if none to two or more than three adenomas are encountered when a check-up colonoscopy is carried out. A check-up one year after the polypectomy and check-ups more frequently than respectively six and three years after polypectomy are not considered to be useful, while each check-up is accompanied by risks and costs. Check-ups can be suspended for patients in whom cumulatively one adenomatous polyp has been removed: from the age of 65 years, for patients in whom cumulatively two adenomas have been removed: from the age of 75 years, and for patients in whom cumulatively three adenomas have been removed check-ups must be continued for as long as the patient's vitality justifies this. Also if no adenomas are encountered during three consecutive check-ups, a suspension of the check-ups can be considered. Separate guidelines apply to patients with genetically determined adenomas.

Adenomatous Polyps↗
PubMed2001

Evaluation of (pre-)malignant colonic abnormalities: endoscopic validation of FDG-PET findings.

The diagnostic accuracy of 2-[(18)F]-fluoro-2-deoxy- D-glucose positron emission tomography (FDG-PET) for the detection of (pre-)malignant lesions of the colon was compared with that of endoscopy. We selected a cohort of 39 patients [13 females and 26 males; mean age 62.3 years standard deviation (SD) 9.6 years] who underwent both FDG-PET and endoscopy (total of 44 procedures) in a 2-year period with a maximum interval between the examinations of 3 months (mean 30 days, SD 28 days). The underlying pathology was colorectal malignancies (24 patients), other malignancies (nine patients) and other disorders (six patients). Follow-up of resected colorectal cancer was the most common reason for the performance of endoscopy. In 19 patients FDG bowel uptake was interpreted as non-physiological, and in 18 patients abnormal findings (adenomatous polyps >3 mm or carcinoma) were detected by endoscopy. Compared with colonoscopy, FDG-PET had a sensitivity of 74% and specificity of 84%. The positive predictive value of FDG-PET was 78%. FDG-PET failed to detect small (diameter 3-10 mm) polyps in four patients. In nine cases abnormal FDG accumulation on PET imaging was the sole reason for performance of an endoscopic procedure. In these cases, endoscopy detected large adenomatous polyps in four patients and carcinomas in two patients, but no abnormalities were detected on endoscopy in the other three patients. There was a good correlation between the location of FDG uptake and endoscopy-positive lesions. FDG-PET is able to detect clinically relevant lesions of the colon. Our study suggests that it can be regarded as a useful adjunct in the non-invasive follow-up of patients with colorectal carcinomas.

Adenoma↗
PubMed2001

MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families.

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and MSH6. The aims of the present study were to compare the risk of developing colorectal, endometrial, and other cancers between families with the various MMR-gene mutations. PATIENTS AND METHODS: Clinical and pathologic data were collected from 138 families with HNPCC. Mutation analyses were performed for all families. Survival analysis was used to calculate the cumulative risk of developing cancer in the various subsets of relatives. RESULTS: Mutations were identified in 79 families: 34 in MLH1, 40 in MSH2, and five in MSH6. The lifetime risk of developing cancer at any site was significantly higher for MSH2 mutation carriers than for MLH1 mutation carriers (P < .01). The risk of developing colorectal or endometrial cancer was higher in MSH2 mutation carriers than in MLH1 mutation carriers, but the difference was not significant (P = .13 and P = .057, respectively). MSH2 mutation carriers were found to have a significantly higher risk of developing cancer of the urinary tract (P < .05). The risk of developing cancer of the ovaries, stomach, and brain was also higher in the MSH2 mutation carriers than in the MLH1 mutation carriers, but the difference was not statistically significant. CONCLUSION: Pending large prospective studies, the extension of the current surveillance program in MSH2 mutation carriers with the inclusion of the urinary tract should be considered.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Effect of resistant starch on potential biomarkers for colonic cancer risk in patients with colonic adenomas: a controlled trial.

Resistant starch decreases the concentration of secondary bile acids in the feces and the proliferation rate of colonic mucosal cells in healthy volunteers. This may reduce the risk of colon cancer. We investigated 23 patients with recently removed colonic adenoma(s) in a controlled parallel trial. They consumed 45 g of maltodextrin per day as placebo for four weeks and were randomly assigned to either 45 g of native amylomaize starch, containing 28 g of resistant starch type II or 45 g of maltodextrin for another four weeks. No effect on colorectal cell proliferation, fecal wet and dry weights, pH, and short-chain fatty acid excretion was seen. The bile acid concentration in fecal water decreased by 15% (P = 0.048) and the percentage secondary bile acids decreased by 14% (P = 0.002) on resistant starch relative to placebo. Whether this has a substantial role in colon cancer prevention in these patients remains to be established.

Adenoma↗
PubMed2001

The glutathione biotransformation system and colorectal cancer risk in humans.

Evidence for a protective role of the glutathione biotransformation system in carcinogenesis is growing. However, most data on this system in relation to colorectal cancer originate from animal studies. Here we review the human data. In humans, a significant association was found between glutathione S-transferase (GST) activity in the mucosa along the gastrointestinal tract and the corresponding tumour incidence. Low activity was correlated with high tumour incidence and vice versa. Also, in normal colonic mucosa, GST activity is lower in patients at risk of colon cancer than in healthy controls and therefore interventions which increase the glutathione detoxification capacity may reduce cancer incidence. Consumption of vegetables and fruit is associated with a lower risk of colorectal cancer. Human intervention studies showed that (components from) vegetables induced colonic glutathione detoxification capacity. Such an effect could contribute to a lower colon cancer risk, but further data are needed. The human GSTs consist of four main classes--alpha (A), mu (M), pi (P) and theta (T)--each of which is divided into one or more isoforms. Functional polymorphisms are known for the GST genes M1, P1 and T1 and they all lead to less active enzymes compared to the wild-type gene products. However, studies that compared these GST polymorphisms in relation to colon cancer risk were not conclusive with respect to an increased or decreased risk of a particular genotype. Diet or medication can also influence the expression levels of specific isoenzymes and the effect of such interventions on cancer risk deserves more attention.

Biotransformation↗
PubMed2000

[Aortic stenosis and intestinal blood loss from angiodysplasia: valve replacement is a therapeutic option].

Three patients, men aged 67, 68 en 61, had for many years suffered from recurrent iron deficient anaemia and were found to have an aortic stenosis. Coloscopy identified angiodysplastic lesions, and we suspected additional lesions in the small intestine. Despite surgical and endoscopic treatment, gastrointestinal bleeding recurred. Replacement of the stenosed aortic valve with a bioprosthesis led to a recovery in the haemoglobin levels of all three patients. Angiodysplasias are a common source of gastrointestinal bleeding with an invisible origin. Data from the literature suggest an association between aortic stenosis and angiodysplasia although epidemiological evidence is lacking.

Aged↗
PubMed2000

A combination of anti-CD3 and anti-CD7 ricin A-immunotoxins for the in vivo treatment of acute graft versus host disease.

This study evaluated the anti-graft versus host disease (GVHD) potential of a combination of immunotoxins (IT), consisting of a murine CD3 (SPV-T3a) and CD7 (WT1) monoclonal antibody both conjugated to deglycosylated ricin A. In vitro efficacy data demonstrated that these IT act synergistically, resulting in an approximately 99% elimination of activated T cells at 10(-8 )mol/L (about 1.8 microg/mL). Because most natural killer (NK) cells are CD7(+), NK activity was inhibited as well. Apart from the killing mediated by ricin A, binding of SPV-T3a by itself impaired in vitro cytotoxic T-cell cytotoxicity. Flow cytometric analysis revealed that this was due to both modulation of the CD3/T-cell receptor complex and activation-induced cell death. These results warranted evaluation of the IT combination in patients with refractory acute GVHD in an ongoing pilot study. So far, 4 patients have been treated with 3 to 4 infusions of 2 or 4 mg/m(2) IT combination, administered intravenously at 48-hour intervals. The T(1/2) was 6.7 hours, and peak serum levels ranged from 258 to 3210 ng/mL. Drug-associated side effects were restricted to limited edema, fever, and a modest rise of creatine kinase levels. One patient developed low-titer antibodies against ricin A. Infusions were associated with an immediate drop of circulating T cells, followed by a more gradual but continuing elimination of T/NK cells. One patient mounted an extensive CD8 T-cell response directly after treatment, not accompanied with aggravating GVHD. Two patients showed nearly complete remission of GVHD, despite unresponsiveness to the extensive pretreatment. These findings justify further investigation of the IT combination for treatment of diseases mediated by T cells. (Blood. 2000;95:3693-3701)

Acute Disease↗