K. Miyazaki

Expression of the thymidine phosphorylase gene in epithelial ovarian cancer

SummaryThymidine phosphorylase (TP) is associated with angiogenesis and the progression of solid tumours. High intracellular levels of this enzyme indicate increased chemosensitivity to pyrimidine antimetabolites. TP gene expression in 56 cases of epithelial ovarian cancer (27 of serous, 10 mucinous, 12 endometrioid, five clear cell and two undifferentiated) were analysed by polymerase chain reaction of RNA after reverse transcription. These included eight of low malignant potential. Twenty were stage I, four stage II, 27 stage III and five stage IV. The level of TP gene expression was presented by the relative yield of the TP gene to the β2-microglobulin gene. TP gene expression ranged from 0.19 to 5.38 (median 0.93). The value of TP gene expression in stage III–IV was significantly higher than that of TP gene expression in stage I–II (P = 0.0005). Histological grade significantly associated with TP gene expression (P = 0.008), but histological subtype did not (P = 0.166). A follow-up study of 34 cases after complete resection of the primary tumours by surgical operation was performed. TP gene expression of the cases with recurrence showed significantly higher levels compared to cases without recurrence (P = 0.049). Survival data were available for 47 of the 56 patients. The prognosis of the patients with high TP gene expression (equal to, or greater than, median) was to be significantly worse than patients with low TP gene expression (less than median) (P = 0.021). The TP gene expression level may play one of the key roles in the biology of ovarian epithelial cancer and define a more aggressive tumour phenotype. A new therapeutic intervention mediated by TP protein activity is anticipated.

Persistent pulsation in a fetal great vessel after complete cardiac arrest

Preterm delivery is a major cause of neonatal morbidity and mortality that especially affects multiple gestations. This potentially devastating complication can often be predicted from sonographic evidence of shortened cervical length. However, the data remain limited and no guidelines exist on the optimal timing and frequency of sonographic surveillance in triplet pregnancies. Preterm delivery in triplets has been found to be associated with shortened cervical length diagnosed by transvaginal ultrasound at various gestational ages: between 12 and 20 weeks1, between 16 and 20 weeks2, between 15 and 24 weeks3, or at 23 weeks’ gestation4. Furthermore, once cervical shortening has been diagnosed the clinical question becomes whether to perform a cervical cerclage or manage the pregnancy expectantly. Most evidence for multiple gestations is derived from studies of twins5, where ultrasound-indicated cerclage does not appear to prolong gestation or improve outcome. In triplets, routine prophylactic cerclage placement has not been found to be associated with significant pregnancy prolongation6. We have previously presented our preliminary data on 24 triplet pregnancies that were followed with biweekly transvaginal ultrasonography7. We demonstrated that patients diagnosed with cervical shortening following biweekly sonographic surveillance were at greater risk of delivering earlier and having babies that weighed less than patients without a shortened cervix. However, within the subset of patients with a short cervix, the placement of cervical cerclage did not appear to affect gestational age at delivery or neonatal outcome. We have since recruited more patients and completed our data analysis, and we present here our final results. We analyzed a total of 50 triplet gestations that underwent biweekly transvaginal ultrasound assessment of cervical length at between 11 + 1 and 28 + 3 weeks’ gestation. Of these, 24 (48.0%) were diagnosed with a short cervix, defined as a shortest cervical length of ≤ 25 mm. These patients went on to deliver 24 days earlier (P = 0.001), have babies that weighed 451 g less (P < 0.001) and had lower 1-min (P < 0.001) and 5min (P = 0.006) Apgar scores, compared with patients without cervical shortening. Once diagnosed with a shortened cervix and following appropriate counseling, 11 of the 24 patients (45.8%) underwent cervical cerclage placement at an average gestational age of 20 + 4 weeks, whereas the remaining patients were managed expectantly. When comparing the two groups (Table 1), cervical cerclage did not appear to affect gestational age at delivery, birth weight, 1or 5-min Apgar scores or fetal demise (all, P > 0.05). Statistical analysis was performed using the Student’s t-test for continuous Gaussian variables and chi-square test for categorical variables (Stata v.11, StataCorp LP, College Station, TX, USA). We can thus conclude that, in triplet pregnancies, transvaginal ultrasound ascertainment of a shortened cervix at between 11 + 1 and 28 + 3 weeks’ gestation is associated with an increased risk of preterm delivery and poorer neonatal outcome. However, once identified, these patients do not benefit from ultrasound-indicated cervical cerclage placement and can instead be safely managed expectantly.