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.

Discordant uterine artery velocity waveforms as a predictor of subsequent miscarriage in early viable pregnancies.

OBJECTIVE: Our purpose was to determine whether an abnormal uterine perfusion pattern was associated with subsequent pregnancy loss after fetal cardiac activity was documented. STUDY DESIGN: Pulsatility indexes of both the right and left uterine arteries were obtained by transvaginal color Doppler ultrasonography in 318 consecutive viable pregnancies between 6 and 12 weeks' gestation. The Delta uterine artery pulsatility index value, expressed as the highest uterine artery pulsatility index value minus the lowest value, was calculated for each pregnancy. Women were subsequently classified as having continuing pregnancies or pregnancy loss before 20 weeks' gestation. To predict subsequent pregnancy loss, Doppler findings were adjusted for maternal age, history of previous abortion, presence of subchorionic hematoma, embryonic bradycardia, and gestational age by means of multivariate logistic regression analysis. RESULTS: Twenty-four pregnancies (8%) were spontaneously aborted before 20 weeks' gestation. Both Delta uterine artery pulsatility index (odds ratio 2.9, 95% confidence interval 1.5-5.8) and history of previous abortion (odds ratio 3.1, 95% confidence interval 1.2-8.2) were significantly associated with pregnancy loss in the multivariate logistic regression analysis. The sensitivity and specificity of the multivariate logistic regression model to predict abortion were 75% and 85%, respectively, significantly higher than the diagnostic performances of qualitative and quantitative variables considered individually. CONCLUSION: Discordant uterine artery pulsatility indexes in the first trimester were strongly associated with subsequent pregnancy loss. This suggests that uterine ischemia may be implicated in certain cases of early pregnancy loss after documentation of fetal cardiac activity during the first trimester.

Uterine artery blood flow velocity waveforms in pregnant women with müllerian duct anomaly: a biologic model for uteroplacental insufficiency.

OBJECTIVE: The purpose of this study was to determine whether there are demonstrable alterations in uterine artery blood flow in pregnant women with müllerian duct anomaly. STUDY DESIGN: Flow velocity waveforms obtained from the placental and nonplacental uterine arteries were studied at 18 to 24 weeks' gestational age in 15 pregnant women with müllerian duct anomaly and in 30 controls. The systolic/diastolic ratios were compared and correlated with the degree of placental laterality and perinatal outcome. RESULTS: Systolic/diastolic ratio in the uterine artery was abnormal in 80% of the cases and in 10% of controls (p < 0.0001). A completely lateral placenta was found in 10 of 15 women of the study group and only in 1 of the 30 controls (p < 0.0001). Women with müllerian duct anomaly had higher systolic/diastolic ratios in the nonplacental uterine artery than those with a normal uterus (median 4.3, range 2.0 to 7.4 vs median 2.8, range 2.0 to 4.0; p < 0.001). Twelve of 15 women of the study group had poor perinatal outcome compared with 4 of the 30 controls (p < 0.001). Among those women with poor perinatal outcome, 11 of 12 (92%) in the study group and only 1 of the 4 (25%) in the control group had an abnormal systolic/diastolic ratio in the uterine arteries (p < 0.05). CONCLUSION: There is a clear association between placental laterality and high systolic/diastolic ratio in the nonplacental uterine artery in pregnant women with müllerian duct anomaly who had poor perinatal outcome. This finding suggests that unilateral placental implantation could lead to functional exclusion of one uterine artery from the uteroplacental circulation and could explain pregnancy complications in women with developmental fusion defects of the uterus.

[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.

[Color Doppler of the utero placental territory and its relationship with the placental localization: normal and elevated resistance groups]. / Doppler color del territorio útero-placentario y su relación con la ubicación placentaria: grupos de resistencia normal y elevada.

Forty two pregnancies of gestational age between 20 and 40 weeks were studied, 26 with normal uterine artery resistance; Group A, and 16 with elevated UA resistance; Group B. Three categories of placental location were established: Type I; central, Type II; partially lateralized including uterine midline, Type III; completely lateralized not including uterine midline. A Diasonic doppler duplex color equipment was used to assess the systole/diastole ratio (s/d ratio). Five different pints of the uteroplacental vascular territory were evaluated in each patient; right and left bottom uterine artery (cervico ithsmical union), right and left top UA (laterally outstanding point of the uterine wall), and inter villous space. The results were analyzed with Statview (Macintosh) statistics software. Placental Type II, prevailed on Group A, Type III prevailed on Group B, Types II and III were predominantly located on the right side of the uterus. S/D ratio was higher in Group B than in Group A in all five sites. S/D rel was higher on left side than on right side measurements. On Group B, left placental side patients had significantly higher s/d rel on non placental uterine artery than right placental side patients. When one altered uterine Doppler flow value is found, all the uteroplacental vascular territory show a high resistance patterns. The lateral placental location patterns tend to express higher resistance values. Right lateral placental locations have even higher resistance values than left ones. The placental location classification is suggested as a screening method for detecting the group of patients in risk of having altered values of Uterine Doppler Flow Velocimetry.

[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)

[Doppler velocimetry: perinatal results according to an integral evaluation of resistances]. / Velocimetría Doppler: resultados perinatales según valoráción integral de resistencias.

The experience with 180 high-risk pregnancies evaluated with Doppler velocimetry in Rancagua Regional Hospital, classified according to an original integral resistance evaluation table, is presented. Perinatal outcome is analyzed in relation to this classification, demonstrating a high correlation between progressive increase of resistance and poor perinatal outcome, evidenced as proportion of SGA newborns, non-reactive NST, low five-minute Apgar score, admission to neonatology or perinatal death, with good sensibility, specificity and predictive values.

[Doppler velocimetry of the arcuate arteries in adolescent pregnant women: predictive value in small for gestational age newborn infants]. / Velocimetría Doppler de arterias arcuatas en embarazadas adolescentes: valor en la predicción de recién nacidos pequeños para la edad gestacional.

A prospective study on 25 adolescent pregnant women was carried out. A single measurement of the systolic-diastolic ratio (S/D) was taken using continuous Doppler on arcuate arteries on both sides of the uterus. All measurements were taken after the 16th week of amenorrhea. The relationship between Doppler velocimetry and birthweight was established. Seven newborns were small for gestational age. The sensitivity of this method was 94.4% and specificity was 57.1%. Positive predictive value was 80.0% while negative predictive value was 85.0%. The importance of measuring both arcuate arteries and determining the site of placental insertion for proper interpretation of results is stressed.