The favorable effect of activating NOTCH1 receptor mutations on long-term outcome in T-ALL patients treated on the ALL-BFM 2000 protocol can be separated from FBXW7 loss of function.

Precursor T-cell acute lymphoblastic leukemia (T-ALL) remains an important challenge in pediatric oncology. Because of the particularly poor prognosis of relapses, it is vital to identify molecular risk factors allowing early and effective treatment stratification. Activating NOTCH1 mutations signify a favorable prognosis in patients treated on ALL-BFM protocols. We have now tested if NOTCH pathway activation at different steps has similar clinical effects and if multiple mutations in this pathway function synergistically. Analysis of a validation set of 151 T-ALL patients and of the total cohort of 301 patients confirms the low relapse rate generally and the overall favorable effect of activating NOTCH1 mutations. Subgroup analysis shows that the NOTCH1 effect in ALL-BFM is restricted to patients with rapid early treatment response. Inactivation of the ubiquitin ligase FBXW7 is associated with rapid early treatment response and synergizes with NOTCH1 receptor activation. However, the effect of FBXW7 inactivation is separable from NOTCH1 activation by not synergizing with NOTCH1 mutations in predicting favorable long-term outcome, which can probably be explained by the interaction of FBXW7 with other clients. Finally, the comparison with other European protocols suggests that the NOTCH effect is treatment dependent generally and may depend on the intensity of central nervous system-directed therapy specifically.

Clinical significance of first trimester umbilical cord cysts.

A cystic mass of the umbilical cord was identified by transvaginal sonography in 10 first trimester pregnancies at a mean gestational age of 8 weeks 4 days (range, 8 weeks 1 day to 9 weeks 3 days) and at a mean crown-rump length of 20.5 mm (range, 15 to 25 mm). The cyst was solitary in all cases, the mean diameter was 4.6 mm (range, 3 to 6 mm), and the location was closer to the fetal insertion in two cases, in the middle of the cord in seven cases, and closer to the placental insertion in one case. Gestational sac and yolk sac diameters as well as the fetal heart rate were within normal ranges for gestational age in all cases. Information on detailed second trimester scans was available in nine cases, demonstrating complete resolution of the cyst and normal fetal anatomic survey in each case. These nine pregnancies were followed to delivery, and normal healthy infants were delivered at term in all cases. This series suggests that the incidental detection of umbilical cord cysts in early pregnancy is not associated with an adverse pregnancy outcome.

[Cyto-histologic evaluation of parametrial involvement in cervico-uterine cancer using aspiration puncture guided by transvaginal echography]. / Evaluación cito-histologica del compromiso parametrial en cáncer cérvico-uterino mediante punción aspirativa guiada por ecografía transvaginal.

Vaginal tact is not sufficient for staging the extension of cervical Ca in its adnexal compromise. The use of transvaginal echography with a cytological hystological parametrial biopsy allow the diagnosis to be certified. In 23 cases studied, 21 epidermoid carcinoma and one adenocarcinoma related with of original cervical tumor were revealed. The clinical staging had a 8.3% error margin.

[Usefulness of transvaginal Doppler color in ovarian neoplasms diagnosis]. / Utilidad del Doppler color transvaginal en el diagnóstico de lesiones ováricas.

The vascular resistant evaluation by Doppler waveform is a method used in clinic and research. The neoplastic malignant has an increased growth with an increased amount of neomalignant vessels. The presence of these vessels produce an increase of the transversal section area from the tumoral vascular system, therefore there is a decrease in the vascular resistance. The main objective of this work is to show the usefulness of Doppler waveform as predictor factor of malignity in ovary tumors. Eighteen patients with tumoral mass in the ovary were studied. They were between 21 and 67 years old (mean = 43). The tumoral volume and the flow resistance of blood vessels which irrigated those tumoral mass were evaluated by transvaginal ultrasound with color and pulsed Doppler. The pulsatility index (SD/media) was used. The Chi cuadrado test was used to evaluate the results. The results show the presence of six malignant tumors, three of them with low malignicity and the presence of twelve benign tumors. The age of the patients between both groups (malignant and benign tumors) were significant different (40.7 versus 52 years old, p < 0.001). The mean tumoral volume was 65 ml, with a range of 17 to 225 ml in the group of patients with benign tumors and the mean tumoral volume from patients with malignant tumors was 951 ml with a range of 141 to 3142 ml. The difference in the tumoral in both groups was significative with p < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)