Genetic testing and prevention of hereditary cancer at the MMCI--over 10 years of experience.

Hereditary cancer syndromes are frequently seen in young cancer patients and patients with a positive family history. Genetic testing is important for the identification of high-risk individuals, and for the early introduction of specialized preventive care or prophylactic surgeries. High-risk tumour suppressor genes (BRCA1 and BRCA2) and DNA repair genes (MLH1, MSH2 and MSH6) are responsible for a substantial part of hereditary breast, ovarian and colorectal cancer. Other hereditary cancers are seen less frequently, but genetic testing has increased for many other site-specific cancers and complex syndromes. Genetic centres and molecular genetic laboratories are located mostly within university or regional hospitals. Some genetic centres are private. It is highly recommended (Czech Society for Medical Genetics) that all laboratories are accredited according to ISO 15,189 and that genetic testing of hereditary cancer syndromes is indicated by medical geneticists. The indication criteria and prevention strategies were published in Supplement 22 of Clinical Oncology 2009 (in Czech). Preventive care for high-risk individuals is organized by thirteen Oncology Centres, which provide most of the oncology care in the Czech Republic. Genetic testing and preventive care for high-risk individuals and mutation carriers is covered by health insurance. The molecular genetic laboratory at the MMCI provides molecular genetic testing of BRCA1, BRCA2, CHEK2 for hereditary breast/ovarian cancer, MLH1, MSH2, MSH6 for Lynch syndrome,TP53 for Li-Fraumeni syndrome, CDKN2A for familial malignant melanoma syndrome and CDH1 gene for hereditary diffuse gastric cancer. Other syndromes are tested in specialized laboratories elsewhere.The use of genetic testing is increasing because of more frequent referrals from oncologists and other specialists and the increasing variety of genes tested. However, in some patients the testing is not recommended and other family members are dying because of the late diagnosis of hereditary syndrome. Greater awareness of the importance of genetic testing in oncology is needed.

[Diagnosis of magnesium deficiency in the body, personal experience]. / Diagnostika deficitu horcíku v organismu, vlastní zkusenosti.

Magnesium as a component of a range of enzymatic systems is a very important intracellular cation in the organism. Its monitoring is limited in many observations only to determination of its concentration in blood serum. We have done an analysis of serum and erythrocyte magnesium concentrations in 23 healthy women, 70 healthy men and in 184 patients with ulcerative disease of gastroduodenum. It was proved in all the monitored groups that erythrocyte concentrations of magnesium were lower compared to values which were estimated from serum concentrations in 9 from 23 healthy women, in 3 from 60 healthy men, in 10 from 101 ill men with ulcerative gastroduodenal disease, and in 17 from 83 women with ulcerative gastroduodenal disease. The highest rate of low concentrations of erythrocyte magnesium in healthy women with physiologic concentrations of magnesium in serum was also confirmed by currently created subgroup of healthy women (n = 11) who undergone together with other analysis peroral Mg2+ load test. This test confirmed magnesium deficiency in 10 from 11 women. The results showed there are more frequent deficiencies of magnesium in organisms then it is generally assumed. They also proved the importance of nutrition and regular food in population of healthy, young women.

[Concomitant chemoradiotherapy in the treatment of carcinoma of the uterine cervix]. / Konkomitantní chemoradioterapie v lécbe karcinomu cípku delozního.

Cervical carcinoma represents a serious medical and social problem. Its incidence in the Czech republic is two times higher than it is in countries of the European Union. Initial stages of the disease have the best treatment results. But most of patients at the time of diagnosis have advanced inoperable carcinoma. Radiotherapy plays the main role in the treatment. Even though methods of radiotherapy have developed, treatment results have not been satisfying enough. The aim of chemotherapy is to improve these results. The effectiveness of adjuvant, neoadjuvant and concomitant chemotherapy was studied by number of authors. Concomitant chemoradiotherapy is considered as the most effective treatment. Concomitant weekly application of cis-platinum in the dose of 40-50 mg/m2 is a widely used standard regimen. Radiopotential effect of other cytostatic drugs has been studied in several ongoing trials.

[Concomitant chemoradiotherapy in the treatment of vulvar carcinoma]. / Konkomitantní chemoradioterapie v lécbe karcinomu vulvy.

Vulvar carcinoma belongs between the less frequent gynaecologic malignancies. Despite to the low morbidity its mortality is high. The reason is locally advanced disease at the time of diagnosis. Radical surgery is mutilating for patient. Radiotherapy was not considered as a standard treatment. Recently, due to technical improvement, mega-voltage facilities and knowledge of radiobiology, radiotherapy has become a part of standard treatment modalities. It plays an important role in the curative, adjuvant and palliative treatment. Concomitant chemoradiotherapy has been used since the eighties of the last century to improve results and reduce extent of surgery in locally advanced vulvar carcinomas. Results show that concomitant chemoradiotherapy is a method of choice in the treatment of locally advanced or recurrent disease. Additional studies are necessary to determine the specific categories of patients who would benefit most from concomitant chemoradiotherapy.

Treatment of uterine sarcoma. A survey of 49 patients.

PURPOSE: Surgery, radiotherapy and chemotherapy are employed in the treatment of uterine sarcoma. We claim to evaluate the role of radiotherapy in the treatment of uterine sarcoma. PATIENTS AND METHODS: We report a retrospective study of 49 patients with uterine sarcoma treated from 1990-1999 at Masaryk Memorial Cancer Institute in Brno. All 49 patients had surgery, 19 (38.7%) had adjuvant radiotherapy and 25 (51%) had chemotherapy. Using the FIGO classification: 71.4% had stage I, 6.1% stage II, 16.3%, stage III and 6.1% stage IVa disease. 42.9% of tumors were mixed Müllerian tumors, 34.7% leiomyosarcomas and 22.4% endometrial stromal sarcomas. 12 cases (24.5%) had a local recurrence, 7 (14.3%) had hematogenous dissemination. There was an increased disease free interval (DFI) for patients treated with adjuvant radiotherapy (p = 0.005). The DFI was favourably influenced by the stage of the disease. Of 12 patients with a local recurrence only one had postoperative radiotherapy. Radiotherapy had an impact on overall survival (OS). The five-year OS probability was 51.6% without radiotherapy and 88.9% with radiotherapy (p = 0.0066). CONCLUSION: We conclude that postoperative radiotherapy in our series of patients diagnosed with uterine sarcoma has an impact on locoregional and disease-free progression intervals (LRFI, DFI) and overall survival (OS). The most important prognostic factor is the extend of the disease (stage). Stage I patients have a significantly better survival.