L I H Overbeek

UMC St. Radboud Nijmegen, Nymegen, Gelderland, Netherlands

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Publications (5)11.59 Total impact

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    ABSTRACT: - Lynch syndrome is the most common cause of hereditary intestinal cancer, with a 30-70% risk of colorectal cancer (CRC).- Prevention of CRC by colonoscopy in family members with Lynch syndrome is highly effective; therefore, it is important to trace as many people with this syndrome as possible.- Criteria have been developed in the Netherlands to increase detection of hereditary colorectal cancer in a practically feasible and cost-effective way. Based on these criteria, the pathologist can perform microsatellite instability testing in patients recently diagnosed with CRC.- The criteria are: CRC under the age of 50, second CRC under the age of 70, or CRC under the age of 70 with a concurrent or previous malignancy associated with Lynch syndrome.- For family members and patients diagnosed with CRC more than a year ago, a digital test can be used to determine whether genetic counselling by a geneticist is indicated (www.umcn.nl/verwijzers).
    Nederlands tijdschrift voor geneeskunde 10/2012; 156(42):A4982.
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    ABSTRACT: We investigated success factors for the introduction of a guideline on recognition of Lynch syndrome in patients recently diagnosed with colorectal cancer (CRC) below age 50 or a second CRC below age 70. Pathologists were asked to start microsatellite instability (MSI) testing and report to surgeons with the advice to consider genetic counselling when MSI test or family history was positive. A multicentre cluster-randomised controlled trial (ClinicalTrials.gov, number NCT00141466) was performed in 12 pathology laboratories (clusters), serving 29 community hospitals. All received an introduction to the new guideline. In the intervention group, surgeons received education and tumour test result reminders; pathologists were provided with inclusion criteria cards, an electronic patient inclusion reminder system and feedback on inclusion. Two hundred sixty-six CRC patients were eligible for recognition as at risk for Lynch syndrome. The actual recognition was 18% more successful in the intervention as compared to the control arm (77% (120 of 156) compared to 59% (65 of 110)), with an adjusted odds ratio (OR) = 2.8 (95% confidence interval (CI) 1.1-7.0). The electronic reminder system for pathologists was most strongly associated with recognition of high-risk patients, OR = 4.2 (95% CI 1.7-10.1). An electronic reminder system for pathologists appeared effective for adherence to a new complex guideline and will enhance the recognition of Lynch syndrome.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 04/2010; 456(6):653-9. DOI:10.1007/s00428-010-0907-7 · 2.65 Impact Factor
  • N Hoogerbrugge · L I H Overbeek · J de Hullu · C M Kets · K M Hebeda · M J L Ligtenberg ·
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    ABSTRACT: Endometrial cancer diagnosed at a relatively young age or in a patient with a medical history of colorectal cancer may be indicative of Lynch syndrome. Four women, aged 43, 60, 41 and 54 respectively, with a family history of endometrial or colorectal neoplasm were examined for microsatellite instability (MSI) in tumour tissue with positive results. Subsequently, a mutation was found in one of the DNA mismatch repair genes. Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is caused by a germline mutation in a mismatch repair gene and is an autosomal dominant disorder that is characterized by the development of carcinoma of the endometrium and colorectum at a relatively young age. Until recently, recognition of Lynch syndrome was mainly based on an, often incomplete, family history, but today the presence of MSI in tumour tissue can be used to identify patients at risk for Lynch syndrome. A pathologist can contribute to identifying a patient at risk for Lynch syndrome by initiating MSI testing when: (a) endometrial cancer is diagnosed under the age of 50, (b) a combination of endometrial cancer and colorectal cancer is diagnosed under the age of 70.
    Nederlands tijdschrift voor geneeskunde 07/2007; 151(26):1441-4.
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    ABSTRACT: The cancer risk is unknown for those families in which a microsatellite instable tumour is neither explained by MLH1 promoter methylation nor by a germline mutation in a mismatch repair (MMR) gene. Such information is essential for genetic counselling. Families suspected of Lynch syndrome (n = 614) were analysed for microsatellite instability, MLH1 promoter methylation and/or germline mutations in MLH1, MSH2, MSH6, and PMS2. Characteristics of the 76 families with a germline mutation (24 MLH1, 2 PMS2, 32 MSH2, and 18 MSH6) were compared with those of 18 families with an unexplained microsatellite instable tumour. The mean age at diagnosis of the index patients in both groups was comparable at 44 years. Immunohistochemistry confirmed the loss of an MMR protein. Together this suggests germline inactivation of a known gene. The Amsterdam II criteria were fulfilled in 50/75 families (66%) that carried a germline mutation in an MMR gene and in only 2/18 families (11%) with an unexplained microsatellite instable tumour (P<0.0001). Current diagnostic strategies can detect almost all highly penetrant MMR gene mutations. Patients with an as yet unexplained microsatellite instable tumour likely carry a different type of mutation that confers a lower risk of cancer for relatives.
    British Journal of Cancer 05/2007; 96(10):1605-12. DOI:10.1038/sj.bjc.6603754 · 4.84 Impact Factor
  • L I H Overbeek · L Kapusta · P G M Peer · C L de Korte · J M Thijssen · O Daniels ·
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    ABSTRACT: To renew the echocardiographic reference values of heart dimensions in healthy children. Group 1 consisted of 587 children, of which 361 boys and 226 girls, age from birth to 18 years, body weight over 2500 g, who visited the Pediatric Cardiology outclinic during the period January 2000 till March 2004. All included children were diagnosed as normal, or as having innocent heart murmur. The second group was taken from an earlier study and comprised 160 children (77 boys and 83 girls). The echocardiographic measures were taken from conventional M-mode recording of the left ventricle (LV) parasternal long axis view. End diastolic septal (IVS) and LV posterior wall thickness (LVPW) and end diastolic as well as end systolic LV intracavity dimensions were retrospectively analyzed. The regression lines from all measured sizes are significantly different from those collected in the early eighties. Especially the thickness of the IVS is smaller. The regression lines are independent of gender. New reference values have been found which should replace the presently used ones. There is no difference between boys and girls. Why the muscular wall thicknesses are thinner than found 20 years ago needs to be further explored.
    European Heart Journal – Cardiovascular Imaging 04/2006; 7(2):113-21. DOI:10.1016/j.euje.2005.03.012 · 4.11 Impact Factor