Rational selection of predictive pharmacogenomics test for the Fluoropyrimidine/Oxaliplatin based therapy.

OBJECTIVE: Both Fluoropyrimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat colorectal, ovarian, and gastrointestinal cancers. Nevertheless, the efficacy of FluOx-based therapy is often compromised by the severe risk of neurotoxicity, cardiotoxicity, and gastrointestinal toxicity. Stratification of patients for their individual response to drugs is a promising approach for cancer treatment and cost-effectiveness. Here we evaluate the most recent findings on the most appropriate gene variants related to the toxicity in patients receiving FluOx chemotherapy. MATERIALS AND METHODS: A systematic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted to identify all clinical studies of any association between DPYD and 5-FU correlated to allelic status of 6 validated polymorphisms in five genes Dihydropyrimidine Dehydrogenase (DPYD), Thymidylate Synthase (TYMS), Glutathione S-Transferase (GSTP1), and DNA-repair genes (ERCC2 and XRCC1). RESULTS: The stratification of the patients into three genotype profiles group, who are most likely responders to FluOx treatments, provide informations about toxicity and/or resistance before starting therapy. Also, early evaluation cost of panel testing proposed is averaged about €100,00 per sample. The evaluation costs of genotyping before starting treatment could be a good cost-effectiveness strategy. CONCLUSIONS: Based on the individual genomic profile, the oncologists will have new possibilities, based on the individual genetic profile, to make treatment decisions for their patients and to redefine scheduling and dosage of FluOx-based therapy.

[Digital nerve block anaesthesia: historical development and two cases of finger-tip necrosis, a rare complication]. / Fingerblock-Anästhesie - Uber die geschichtliche Entwicklung und zwei Fälle einer Fingernekrose als seltene Komplikation.

Two cases of finger-tip necrosis following digital blocks are presented. These are rare complications of this technique. Pathogenesis and treatment options are discussed and the literature reviewed. Circulatory problems can be avoided by using adrenalin free anaesthetics, infiltrating at the metacarpal level with small volumes, and using upper-arm tourniquets instead of rubber bands at the phalangeal level.

Evaluation of genotyping methods and the relative cost of pharmacogenomics.

Recently, several methods to assess the quality of cost-effectiveness, cost-utility and cost-benefit in the pharmacogenomic field have become available. A relevant example is the National Institute for Health and Clinical Excellence (NICE). NICE forms a diverse clinical Advisory committee, which stimulates Pharma and Academic communities to produce a robust set of data, including the design and data source, for economic models of personalized healthcare. Personalized medicine includes genomic tests of each patients and their disease into their clinical treatments, so as minimize toxicity and maximize benefits. It is well known that Pharmacogenomics (PG) tests, performed before drug treatment, lower overall medical costs and provide higher quality of life and longer life expectancy. In this issue relative costs of genotyping methods and platforms, were evaluated by "manually cured criteria" due to lack of specific guidelines. Finally, with the progress made in this scenario over the next five years, health decision-making may able to accelerating the translation of genetic technologies into routine clinical laboratory.

[Stomach surgery--are the requirements for specialist in general surgery still realistic?]. / Magenchirurgie--sind die Bedingungen für den Facharzt für allgemeine Chirurgie noch realistisch?

This paper discusses the possibility for a surgical trainee to acquire the necessary experience in gastric operations for his fellowship in general surgery. All operations of the stomach performed at the surgical unit of Lucerne Hospital between January 1994 and September 1997 were analysed retrospectively. Of 184 operations performed only nine were done by a trainee, four of which were gastrostomies and five operations of a perforated ulcer. These results prove the difficulties for a trainee to achieve the required number of operations. Possible solutions would be the acknowledgement of assisted operations for the fellowship in general surgery and/or the limitation of gastric operations performed by the trainee himself to the curriculum for the fellowship in visceral surgery.