Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status.

The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients. We found TP53 mutations in 50 cases (0.2-16.3% VAF), regardless of disease subtype, driver gene status and cytoreduction. Both therapy and TP53 mutations were strongly associated with older age. Over-time analysis showed that the mutations may be undetectable at diagnosis and slowly increase during disease course. Although three patients with TP53 mutations progressed to TP53-mutated or TP53-wild-type AML, we did not observe a significant age-independent impact on overall survival during the follow-up. Further, we showed that complete p53 inactivation alone led to neither blast transformation nor HU resistance. Altogether, we revealed patient's age as the strongest factor affecting low-burden TP53 mutation incidence in MPN and found no significant age-independent association between TP53 mutations and hydroxyurea. Mutations may persist at low levels for years without an immediate risk of progression.

[Ultrasonic staging cervical cancer -a proposal for the standard procedure]. / Ultrazvukový staging karcinomu delozního hrdla - návrh standardního postupu.

OBJECTIVE: To develop guidelines for the ultrasound examination of cervical cancer, including a unified ultrasound terminology. SUBJECT: Original paper. SETTING: Gynecological Oncology Center, Department of Obstetrics and Gynecology, Masaryk University and General Faculty Hospital Brno, and Gynecological Oncology Center, Department of Obstetrics and Gynecology, Charles University in Prague - First Faculty of Medicine and General Faculty Hospital Prague. SUBJECT AND METHOD: The standard diagnostic algo-rithm for examination of cervical cancer in oncogynecology centers in the Czech Republic is based on published studies, own experience (Oncogynecological Center, Department of Gynecology and Obstetrics,1st Medical Faculty, Charles University) and the experiences of a group of ultrasonographers involved in the grant project IGA MZ CR NT13070 focused on the implementation of an oncogynecological ultrasound into clinical practice. Standard ultrasound examination includes two-dimensional real-time ultrasound examination (sagittal and transverse views). Transrectal or transvaginal ultrasound examination is combined with transabdominal ultrasound. Prerequisites are quality ultrasound equipment, a high frequency microconvex linear probe and abdominal convex and linear probe. The examination is performed by an experienced sonographer (level 2 or 3 according to the recommendations of the Ultrasound division of the Czech Society of Obstetrics and Gynecology and the Czech Society of Ultrasound in Obstetrics and Gynecology). Intravenous administration of contrast material or three-dimensional ultrasound examination do not influence accuracy of the examination and is not a prerequisite. CONCLUSION: Based on the consensus of experienced sonographers and a review of the literature, guidelines were created for ultrasound staging of cervical cancer.

[Ultrasound staging of endometrial cancer - recommended methodology of examination]. / Ultrazvukový staging karcinomu endometria - doporucená metodika vysetrení

The extent of the staging surgery in cases of histologically proven endometrial cancer depends on whether the tumor is of high risk or low risk for extrauterine spread and recurrence. There are several significant prognostic factors - histological subtype and grade of dediferentiation from preoperative biopsy and local stage of uterine involvement based on imaging methods. The depth of myometrial invasion and presence of cervical stromal infiltration (local staging) can be assessed by ultrasound with the overall accuracy comparable to that of magnetic resonance. Transvaginal ultrasound enables to vizualize detailed pelvic anatomy and that is why it is considered to be a suitable tool for assessment of local stage of endometrial cancer. It is advisable to use the standardized terminology defined by International Endometrial Tumor Analysis group (IETA) to describe ultrasound findings. The standardized methodology of ultrasound preoperative staging examination based on prearranged protocols is recommended.

[Retrospective analysis of effectiveness of transvaginal ultrasound in the detection of ectopic pregnancy]. / Retrospektivní analýza efektivity diagnostiky ektopické gravidity transvaginálním ultrazvukovým vysetrením.

OBJECTIVE: To evaluate the effectiveness of transvaginal ultrasonographic (US) scan in own group of patients. DESIGN: Retrospective analysis. SETTING: Department of Gynaecology and Obstetrics, 3rd Faculty of Medicine, Charles University and Faculty Hospital Kralovské Vinohrady, Prague. METHODS: We retrospectively evaluated the history, laboratory and ultrasound findings in a group of 115 patients, that have undergone a surgical procedure due to a positive diagnose or suspicion of ectopic pregnancy (EP). In all cases the diagnose of ectopic pregnancy was histologically confirmed. RESULTS: 67% of our patients were nulliparous, 10% of patients had a positive personal history of previous ectopic pregnancy, only 5% of pacients had a record of pelvic inflammatory disease in the past. Histological examination confirmed 96.5% (111/115) tubal, 1.7% (2/115) interstitial, 0.9% (1/115) ovarian and 0.9% (1/115) cervical ectopic pregnancy. Our transvaginal ultrasonography (TVUS) scan was successful in 76.5% (88/115). A pathological adnexal mass was visualised in 67% (77/115) cases. A negative ultrasound finding was observed in 23.5% (27/115) cases. CONCLUSION: The US detection of ectopic pregnancy by a single TVUS examination was successful in 76.5% (88/115) cases. Early detection of ectopic pregnancy by TVUS decreases the risk of rupture of different types of EP, decreases the rate of surgical interventions and also promotes conservative management of ectopic pregnancies.

[Sperm banking before gonadotoxic treatment--11-years experience]. / Kryokonzervace spermatu pred gonadotoxickou lérbou--11 let zkuseností.

INTRODUCTION: The aim of this study was to analyze possible relation of sperm pathology and diagnosis of malignant disease and present our experience of sperm banking programme for cancer patients. DESIGN: Retrospective clinical study. SETTING: Department of Obstetrics and Gynecology, Masaryk University, Brno. MATERIAL AND METHODS: 521 patients (age 26.0 +/- 6.7 years) were referred to our unit by oncology specialists for semen cryopreservation before cancer treatment during 1995-2005. Sperm samples obtained by masturbation were analysed according to guidelines of WHO. Cryoprotective medium and Planer Kryo F 10 were used for standard cryopreservation. National cancer register was used to analyze patients survival. Basic statistics was used for data description and relations among sperm parameters and diagnosis were tested by Kruskal-Wallis ANOVA. Standard intracytoplasmic sperm injection (ICSI) using frozen spermatozoa was used for infertility treatment following malignant disease recovery. RESULTS: Testicular cancer was diagnosed in 45.7% patients, malignant disease of lymphatic and haemopoetic tissue in 32.0% cases--out of them 16.5% Hodgkinps lymphoma. Sperm concentration > or =20 mil/ml had 45.9% men. Severe oligospermia < or =1 mil/ml was found in 23.2% men and azoospermia in 10.0% patients. Severe asthenospermia < or =10% was in 60.8% men. Sperms were retrieved in 76.7% of 30 boys 14 to 16 years old, in 46.7% was concentration lower than 1 mil/ml and in 26.1% sperm motility lower than 1%. Sperm concentration was significantly lower in men with testicular cancer (p = 0.002), differences in sperm motility were insignificant. Cryopreserved samples were used in 30 patients (5.8%), 22 of them in our centre. Intracytoplasmatic sperm injection was used in all cases, 7 clinical pregnancies (31.8%) and 5 deliveries were achieved. In the group of all patients died 62 men (11.9%). CONCLUSION: Cancer patients have high frequency of severe sperm pathology. The lowest sperm concentration was in men with testicular cancer. Only minority of patients return for fertility treatment. Cryopreserved spermatozoa of cancer patients are able to achieve pregnancy by assisted reproduction techniques.