858 research outputs found
Reply: Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients
Cellular mechanisms in basic and clinical gastroenterology and hepatolog
Bewaring van lelieplantgoed : energiebesparing door vermindering van de circulatie
De veruit belangrijkste energiepost bij de teelt van lelies is het elektraverbruik voor koeling en circulatie tijdens de bewaring van november t/m april. Lelieplantgoed wordt bewaard in palletkisten bij een temperatuur van 2-4 oC in de eerste weken na het rooien tot gemiddeld -0.5 oC in de laatste maanden. Enige ventilatie is nodig voor het afvoeren van CO2 , water en warmte die in de ademhaling geproduceerd worden. Tot enkele jaren geleden werd geadviseerd om één keer per dag de celdeur korte tijd open te zetten om op deze manier te ventileren. Tegenwoordig is in veel leliecellen een PVC-pijpje in de buurt van de verdamper aangebracht om wat verse lucht aan te zuigen. De ventilatiebehoefte van lelies is dus kennelijk erg laag vergeleken met die van tulpenbollen, maar niet exact bekend. Doel van de circulatie is het creëren van een over alle kisten gelijkmatig en gunstig bewaarklimaat tussen de bollen in termen van temperatuur, RV, en CO 2 -gehalte. Voor de circulatie worden in de praktijk normen gehanteerd variërend van 50 tot 300 m3 lucht/uur per m3 leliebollen. Groot nadeel van de circulatie is dat de warmteproductie van de systeemventilatoren ook teruggekoeld moet worden. Doel van dit onderzoek is om voor circulatie en ventilatie tot normen te komen waarmee maximaal op energie wordt bespaard zonder dat dit ten koste gaat van de kwaliteit van het lelieplantgoed. Voor de verminderde circulatie is hierbij ook een vergelijking gemaakt tussen de aan/uit regeling en de frequentieregeling
Family history is neglected in the work-up of patients with colorectal cancer: a quality assessment using cancer registry data
In the diagnostic work-up of hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome), high-risk patients can be identified using information from the family history on cancer (‘Amsterdam criteria’ and ‘Bethesda guidelines’). To investigate to what extent the medical specialists apply these criteria to patients with colorectal carcinoma and a suspicion of HNPCC, we collected information on diagnostic work-up of 224 patients of seven hospitals in the region of the Comprehensive Cancer Centre West in Leiden, The Netherlands. These patients were diagnosed with colorectal cancer between 1999 and 2001 and satisfied at least one of the Bethesda guidelines. A complete family history was recorded for 38 of the 244 patients (16%). Patients with a complete family history were more likely to be referred to the Clinical Genetic Centre than those with an incomplete or absent family history (53% vs. 13% and 4%, respectively; P < 0.0001), and more likely to be analyzed for microsatellite instability (MSI), which is a characteristic of HNPCC (34% vs. 6% and 1%, respectively; P < 0.0001). We conclude that the family history is neglected in the majority of patients with colorectal cancer and MSI-analysis is only performed in a small proportion of the patients that meet the guidelines for this analysis
Penetrance of HNPCC-related cancers in a retrolective cohort of 12 large Newfoundland families carrying a MSH2 founder mutation: an evaluation using modified segregation models
<p>Abstract</p> <p>Background</p> <p>Accurate risk (penetrance) estimates for associated phenotypes in carriers of a major disease gene are important for genetic counselling of at-risk individuals. Population-specific estimates of penetrance are often needed as well. Families ascertained from high-risk disease clinics provide substantial data to estimate penetrance of a disease gene, but these estimates must be adjusted for possible specific sources of bias.</p> <p>Methods</p> <p>A cohort of 12 independently ascertained HNPCC families harbouring a founder MSH2 mutation was identified from a cancer genetics clinic in St. John's, Newfoundland, Canada. Carrier status was known for 247 family members but phenotype information on up to 85 additional relatives with unknown carrier status was available; using modified segregation models these additional individuals could be included in the analyses. Three HNPCC-related phenotypes were evaluated as age at diagnosis of: any HNPCC cancer (first cancer), colorectal cancer (CRC), and endometrial cancer (EC) for females.</p> <p>Results</p> <p>Lifetime (age 70) risk estimates for male and female carriers were similar for developing any HNPCC cancer (Males = 98.2%, 95% Confidence Interval (CI) = (93.8%, 99.9%); Females = 92.8%, 95% CI = (82.4%, 99.1%)) but female carriers experienced substantially reduced lifetime risk for developing CRC compared to male carriers (Females = 38.9%, 95% CI = (24.2%, 62.1%); Males = 84.5%, 95% CI = (67.3%, 91.3%)). Female non-carriers had very low lifetime risk for these two outcomes while male non-carriers had lifetime risks intermediate to the female carriers and non-carriers. Female carriers had a lifetime risk of developing EC of 82.4%. Relative risks for developing any HNPCC cancer (carriers relative to non-carriers) were substantially greater for females compared to their male counterparts (Females = 54.8, 95%CI = (4.4, 379.8); Males = 9.7, 95% CI = (0.3, 23.8)). Relative risks for developing CRC at age 70 were substantially greater for females compared to their male counterparts (Females = 23.7, 95%CI = (5.6, 137.9); Males = 6.8%, 95% CI = (2.3, 66.2)). However, the risk of developing CRC decreased with age among both genders.</p> <p>Conclusion</p> <p>The proposed modified segregation-based models used to estimate age-specific risks for HNPCC phenotypes can reduce bias due to ascertainment and missing genotype information as well as provide estimates of absolute and relative risks.</p
Efficacy of early diagnosis and treatment in women with a family history of breast cancer
BACKGROUND: Surveillance programmes for women at increased genetic risk of breast cancer are being established worldwide but little is known of their efficacy in early detection of cancers and hence reduction in mortality. METHODS: Data were contributed from seven centres participating in the EU Demonstration Programme on Clinical Services for Familial Breast Cancer. All breast tumours (n = 161) detected prospectively, from the time of enrolment of women in a screening programme, were recorded. Analysis took account of age at diagnosis, whether tumours were screen-detected or not, their pathological stage and outcome by Kaplan—Meier survival plots. RESULTS: Mean age at diagnosis was 48.6 years. Overall, 75% of tumours were detected in the course of planned examinations. For women under age 50 at diagnosis, this figure was 68%. Eighteen percent were mammographically negative, (23% in patients under age 50). At first (“prevalence”) round and at follow-up screening, 16% and 22% of tumours respectively were carcinoma in situ (CIS) while 27% and 22% respectively had evidence of nodal or distant spread (CaN+). Comparison of screen-detected and other tumours showed that the latter were more frequently mammogram-negative and CaN+. Overall five-year survival was 89% and five-year event-free survival 86%. Five-year event-free survival was 100% for CIS, 88% for invasive cancer without nodal or distant spread and 67% for CaN+. CONCLUSIONS: The majority of cancers arising in women at increased genetic risk of breast cancer can be detected by planned screening, even in those under age 50. Surveillance should include regular expert clinical examination and teaching of “breast awareness” as well as mammography. Attention to the logistics of screening programmes may improve still further the proportion of tumours that are screen-detected. The trend towards earlier pathological stage in tumours detected during follow-up rounds and the preliminary findings on survival analysis suggest that this approach will prove to be of long-term benefit for breast cancer families.publishedVersio
Ethical, social and economic issues in familial breast cancer: a compilation of views from the EC biomed II demonstration project
ABSTRACT:
Demand for clinical services for
familial breast cancer is continuing to rise across
Europe. Service provision is far from uniform and, in
most centres, its evolution has been determined by
local conditions, specifically by local research
interests, rather than by central planning. However, in
a number of countries there is evidence of progress
towards co-ordinated development and audit of clinics
providing risk assessment, counselling, screening and,
in some cases, prophylactic intervention. Much
important information should emerge from continued
observation and comparative assessment of these
developments.
In most countries for which relevant data are
available, there is a distinct bias towards higher social
class among those who avail themselves of clinic
facilities (in line with findings from many other
health-promotion initiatives). This should be
addressed when considering future organisation of
clinical services.
Molecular genetic studies designed to identify the
underlying mutations responsible for familial breast
cancer are not generally regarded as part of the clinical
service and are funded through research grants (if at
all). Economic considerations suggest that there is a
case for keeping this policy under review.
Familial cancers throw into sharp relief certain ethical
and legal issues that have received much recent
attention from government advisory bodies, patients
’
representatives, professional commentators and the
popular media. Two are of particular importance;
first, the right to gain access to medical records of
relatives, in order to provide accurate risk assessment
for a given family member, versus the right to privacy
in respect of personal medical information and,
second, the obligation (or otherwise) to inform family
members of their risk status if they have not actively
sought that knowledge. The legal position seems to
vary from country to country and, in many cases, is
unclear. In view of pressures to establish uniform
approaches to medical confidentiality across the EC, it
is important to evaluate the experience of participants
in this Demonstration Programme and to apply the
principle of
“
non-malfeasance
”
in formulating regu-
lations that should govern future practice in this field.
Data on economic aspects of familial breast cancer are
remarkably sparse and outdated. As evidence accrues
on the influence of screening and intervention
programmes on morbidity and mortality, there is a
strong case for evaluating the cost-effectiveness of
different models of service provisi
Low frequency of defective mismatch repair in a population-based series of upper urothelial carcinoma
BACKGROUND: Upper urothelial cancer (UUC), i.e. transitional cell carcinomas of the renal pelvis and the ureter, occur at an increased frequency in patients with hereditary nonpolyposis colorectal cancer (HNPCC). Defective mismatch repair (MMR) specifically characterizes HNPCC-associated tumors, but also occurs in subsets of some sporadic tumors, e.g. in gastrointestinal cancer and endometrial cancer. METHODS: We assessed the contribution of defective MMR to the development of UUC in a population-based series from the southern Swedish Cancer Registry, through microsatellite instability (MSI) analysis and immunohistochemical evaluation of expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6. RESULTS: A MSI-high phenotype was identified in 9/216 (4%) successfully analyzed patients and a MSI-low phenotype in 5/216 (2%). Loss of MMR protein immunostaining was found in 11/216 (5%) tumors, and affected most commonly MSH2 and MSH6. CONCLUSION: This population-based series indicates that somatic MMR inactivation is a minor pathway in the development of UUC, but tumors that display defective MMR are, based on the immunohistochemical expression pattern, likely to be associated with HNPCC
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Utilisation of prophylactic mastectomy in 10 European centers
ABSTRACT:
Increasingly women at high risk of
breast cancer are opting for prophylactic surgery to
reduce their risks. Data from 10 European centres that
offer a risk counselling and screening service to
women at risk show different approaches to the option
of preventive surgery, although most centres adhere to
a protocol including at least two risk counselling
sessions and a psychological assessment. Thus far the
combined centres have data on 174 women who have
undergone prophylactic mastectomy with in excess of
400 women years of follow up. Operations were
carried out on women with lifetime risks of 25–80%,
with an average annual expected incidence rate of 1%
per women. No breast cancers have occurred in this
cohort. Long term follow up on an extended group of
women will be necessary to truly address the risk of
subsequent breast cancer and the psychological
sequelae
MEN-2 Syndrome: The Value of Screening and Central Registration; A Study of Six Kindreds in The Netherlands
Since 1975, six families with the MEN-2A syndrome including 66 patients have been identified in The Netherlands. All these patients underwent thyroidectomy for C-cell hyperplasia and/or medullary thyroid carcinoma (MTC); eight were symptomatic (Group A), 51 were relatives of patients found to be affected (Group B), and seven had had a negative screening test that became positive (Group C). To assess the effect of screening, we compared these groups with respect to the occurrence of metastatic MTC at thyroidectomy and the results of the postoperative calcitonin (CT) tests. We found that 87% of Group A, 37% of Group B; and none of Group C had metastatic disease at surgery. The cure rates in these three groups with MEN-2A, as determined by stimulated CT measurement, was 0%, 51%, and 100%, respectively. From these results it may be concluded that screening can lead to the detection of MTC at an earlier stage which in turn could permit curative treatment and improvement of both prognosis and life expectancy. The need for supervision of affected families by central registration to guarantee the continuity of screening is stressed
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