Predictive Genetic Testing for Hereditary Breast and Colorectal CancerrnAn AssessmentrnrnAim and Methodsrn• The aim of this health technology assessment was to analyse the current scientific and genetic counselling situation about predictive genetic testing for hereditary breast and colorectal cancer. Predictive genetic testing will be possible for several common diseases in the future and questions related to financial issues and quality standards will be raised.rn• This report is based on a systematic literature research using several databases (e.g. EmBase, Medline, Cochrane Library) and on a specific health technology assessment (CCOHTA) resp. review (American Gastroenterological Ass.). Laboratory test methods, early detection methods and the benefit from prophylactic interventions were well directed analysed and social consequences were interpreted.rnBackgroundrn• Breast and colorectal cancer are counted among the most frequently cancer diseases. Most of them are based on random accumulation of risk factors, 5-10% show a familial determination. A hereditary modified gene is responsible for the increased cancer risk. In this families high tumour frequency, young age at diagnosis and multiple primary tumours are remarkable.rnResults and Reflectionrn• Genetic diagnosis: The sequence analysis is the gold standard. Denaturing high performance liquid chromatography is a quick alternative method. The identification of the responsible gene defect in an affected family member is important. If the test result is positive there is an uncertainty about if the disease will occur, when and in which degree founded in the geno-/phenotype correlation. The individual risk estimation is based upon empirical evidences. The test results have effects on the whole family. rn• Prevention/early detection: At the moment primary prevention is possible for familial adenomatous polyposis (celecoxib, prophylactic colectomy) and for hereditary mamma carcinoma (prophylactic mastectomy). The so-called preventive medical check ups are early detection examinations. For colorectal cancer the evidence about early detection methods is better than for breast cancer.rn• Prophylactic surgical interventions: Prophylactic mastectomy (PM) reduces the relative breast cancer risk by approximately 90%. The question is if PM influences on mortality. The acceptance of PM depends on culture. Colectomy can be used as a prophylactic (FAP) and therapeutic method. After operations the cancer risk remains high and so early detection examinations are still necessary.rn• Evidence based statements: The evidence is often fragmentary and from limited quality. For objective test result presentations information about sensitivity, specifity, positive predictive value, and number needed to screen resp. treat are necessary.rn• Reflections: New identifications of mutations and demand creation will result in an increase of predictive genetic counselling and testing. There is a gap between predictive genetic diagnosis and the prediction, prevention, early detection and surgical interventions. These circumstances require a basic strategy. Since predictive genetic diagnosis is a very sensitive issue it is important to deal carefully with it in order to avoid inappropriate hopes. Thus, media, experts and politicians have to consider opportunities and limitations in their daily decision-making processes.rn

Immunoglobulins in Transplant MedicinernPrevention and Therapy of Cytomegalovirus InfectionsrnAn AssessmentrnrnBackgroundrnCytomegalovirus (CMV) infections are one of the most common infection complications of transplant recipients. In immune competent persons CMV infections are usually asymptomatic but in immune compromised patients there can be fatal consequences. CMV infections are linked to graft dysfunction and graft loss. The most favourable prophylactic treatment/therapy regime and the starting point of the intervention are under long lasting discussion.rnrnAim and MethodsrnThe aim of this health technology assessment (HTA) was to analyse the clinical effectiveness of immunoglobulins (IG) for prevention/therapy of CMV infections in transplant recipients and to compare IG with other prevention/therapy regimes (virustatica, e.g. Ganciclovir) with regard to clinical effectiveness and cost efficiency. This assessment is based on a systematic review and a meta analysis. Additionally basic knowledge on CMV infection, frequency of transplantations and cost issues are analysed.rnrnResultsrn• With IG there is a significant reduction of CMV infections and diseases in comparison with placebo or no prophylactic treatment/therapy. rn• A comparison of effectiveness based on a systematic review and meta analysis gives no evidence that IG are more effective than virustatica. There is also no evidence for additional effects of IG in antiviral therapy.rn• A review of cost-efficieny/clinical effectiveness studies shows that virustatica are the most cost efficient option for prophylactic treatment/therapy of CMV infections.rn rnrnConclusiornBefore clinical symptoms appear the avtive CMV infection can already be diagnosed by laboratory tests. This allows for a combined CMV management consisting of risk adapted prophylactic treatment in high risk groups and the start of preemptive therapy. For risk evaluation the most important citeria are: CMV antibody constellation between donor and recipient, the type of immune suppressive therapy and the transplanted organ itself. Despite lower toxicity of IG this added value is only marginal because of the many times higher price and the similar, inclining lower clinical effectiveness in comparison to virustatica (e.g. Ganciclovir). From the clinical and economical point of view systematic decisions in the CMV management are necessary: analysis of the actual situation, compilation of working papers for concrete internal standards founded on evidence based guidelines with documentation, including patients in well designed, multicentric studies and considering the establishment of a CMV co-ordinator.rn