Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?

BACKGROUND: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. METHODS: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). RESULTS: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. CONCLUSIONS: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

Maternal thrombophilia and the risk of recurrence of preeclampsia.

OBJECTIVE: The aim of this prospective study was to determine the impact of thrombophilia on the recurrence of preeclampsia. STUDY DESIGN: In a multicenter, observational, cohort design, 172 white patients with a previous pregnancy complicated by preeclampsia were observed in the next pregnancy. They were evaluated for heritable thrombophilia (factor V Leiden and factor II G20210A mutations, protein S, protein C, and antithrombin deficiency), hyperhomocystinemia, lupus anticoagulant, and anticardiolipin antibodies. Development of preeclampsia and maternal complications and both gestational age at delivery and birthweight were recorded. RESULTS: Sixty women (34.9%) showed the presence of a thrombophilic defect. They had a higher risk for the recurrence of preeclampsia (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.2-5.1), compared to patients without thrombophilia. Similar findings were observed considering only heritable thrombophilia. Thrombophilic patients were at increased risk for the occurrence of very early preterm delivery (< 32 weeks; OR, 11.6; 95% CI, 3.4-43.2). CONCLUSION: When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management.

17alpha-hydroxy-progesterone effects on cervical proinflammatory agents in women at risk for preterm delivery.

We evaluated if the inhibitory effect of 17alpha-hydroxyprogesterone caproate (17P) on cervical ripening is mediated by cervical proinflammatory agents. Women with singleton pregnancy and intact membranes, between 25 and 33 weeks + 6 days, were randomly allocated either to observation (22 cases, controls) or to receive 341 mg of intramuscular 17P (23 cases, 17P group), twice a week, until 36 weeks. Just before randomization, 7 and 21 days later, a cervical swab for interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and nitrates/nitrites (NOx) assays was collected. Moreover, an ultrasound measure of cervical length (CL) was performed at the same time. At randomization, both groups of women showed similar levels of cervical ILs and NOx. In the 17P group, cervical IL-1beta levels were significantly decreased at day 21 ( P = 0.036); in controls, they remained stable throughout the observation period. There was no significant change in IL-6, IL-8, TNF-alpha, and NOx in either group. Women in the control group had a progressive CL shortening until day 21 (median shortening of 4 mm), and this shortening was significantly less in the 17P group (median shortening of 2 mm; P = 0.017). In patients at risk of preterm labor, high-dose 17P simultaneously inhibits both cervical proinflammatory IL-1beta secretion and the progressive shortening of the cervix.

Elective cervical ripening in women beyond the 290th day of pregnancy: a randomized trial comparing 2 dinoprostone preparations.

OBJECTIVE: To determine the better performer among cervical ripening agents for the elective induction of labor. STUDY DESIGN: An open-label, randomized study was done in consecutive patients undergoing elective induction of labor at the 41st week and beyond. Inclusion criteria were: singleton pregnancy, gestational age ascertained through first-trimester ultrasound, Bishop score <4 and nulliparity. Exclusion criteria were: oligohydramnios, maternal/fetal disorder or pregnancy complication, previous uterine surgery, rupture of membranes and presence of uterine activity. Patients received either slow-release dinoprostone vaginal insert (VI) or 0.5-mg dinoprostone intracervical (IC) gel, twice, 6 hours apart. RESULTS: Women receiving VI showed increased risk of entering labor without further stimulation (OR = 6.48, 95% CI 2.06-21.67, p < 0.001) and delivering vaginally within 24 hours (OR = 2.71, 95% CI 1.19-6.21, p = 0.01) in comparison to those receiving IC gel. A stay in the hospital (> 4 days) was more prevalent in women treated with IC gel in comparison to those treated with VI (OR = 2.35, 95% CI 1.04-5.37). CONCLUSION: Preinduction cervical ripening with the dinoprostone slow-release vaginal insert is associated with a hight rate of women undergoing vaginal delivery within 24 hours, with a shorter stay. Considering its good performance, the dinoprostone slow-release vaginal insert is the first choice for elective induction of labor in postdate pregnancy.

Effects of three different stimulations (acupuncture, moxibustion, acupuncture plus moxibustion) of BL.67 acupoint at small toe on fetal behavior of breech presentation.

The aim of the study was to evaluate cardiovascular effects and fetal behavior during moxibustion, acupuncture or acupuncture plus moxibustion applied on the BL.67 acupoint of women (beside the outer corner of the 5th toenail) in fetal breech presentation. During the acupoint stimulation (20 min, two times a week), the women were submitted to computerized non-stress test. Fourteen cases were treated by both acupuncture and moxibustion, 15 cases by moxibustion and 10 cases by acupuncture. In 56% of cases, fetal position was converted from breech position to cephalic one; the success share was 80% for moxibustion, 28% for acupuncture, 57% for acupuncture plus moxibustion; the conversion, on average, was achieved after 3 sessions. Statistical analysis indicated that acupuncture plus moxibustion was able to reduce fetal heart rate during the application of stimuli while acupuncture and moxibustion separately did not affect such parameter. Moreover, moxibustion and acupuncture with moxibustion reduced fetal movements while acupuncture only appears ineffective. The present study suggests that fetal movements were reduced by both acupuncture plus moxibustion and moxibustion and that fetal heart rate was reduced just by acupuncture plus moxibustion. The mechanisms leading the effect on fetal heart rate and fetal movements remain to be clarified. Even though further studies are needed, such preliminar report mainly investigated the impact of different stimula on the BL.67 acupoint. Unfortunately these small series of data do not allow us to draw any conclusion about the effectiveness of the different treatments.

Induction of labor at term using isosorbide mononitrate simultaneously with dinoprostone compared to dinoprostone treatment alone: a randomized, controlled trial.

OBJECTIVE: We aimed to determine whether isosorbide mononitrate (IMN) given simultaneously with dinoprostone in term pregnancies is superior to dinoprostone alone to promote delivery. STUDY DESIGN: One hundred and twenty nulliparous women at term were randomly assigned to receive per vaginam IMN 40 mg or placebo in addition to 3 mg dinoprostone 2 times daily for up to 2 days. Analysis was by intention to treat. RESULTS: Baseline characteristics of both groups were comparable. The induction to delivery intervals did not differ between the IMN and the placebo group (26.4 +/- 14.4 vs 23.4 +/- 14.8 hours, P = .408). IMN resulted in more headache compared to placebo (32/55 [58.2%] vs 2/55 [3.6%], P < .001). CONCLUSION: Vaginally administered IMN does not play a role in promoting delivery in term pregnancy if given at the same time as dinoprostone. This might reflect its relaxant effect on the uterine fundus, which may overcome its cervical softening effect.

Changes in cervical nitric oxide concentration correlate with Bishop score and cervical length modifications in prostaglandin E2-mediated induction of labor.

OBJECTIVE: Nitric oxide (NO) plays a fundamental role in cervical ripening and it is synthesized in the human cervix. We studied the effect of the dinoprostone on cervical NO release in pregnant women, and we investigated the relationship between cervical NO metabolites, cervical length, and Bishop score. METHODS: Seventy-seven women underwent induction of labor at > or = 37 weeks of gestation, due to post-term pregnancy (23.8%), oligohydramnios (36.3) or preeclampsia (29.9%). Cervical fluid samples for NO metabolites (NOx), Bishop score, and cervical length were assessed immediately before (time 0 [T0]) and 6 hours after (T6) the local application of dinoprostone, a commercially available prostaglandin E2 (PGE2) analog. RESULTS: The mean patients' age was 34 +/- 3.2 years, mean gestational age at enrollment was 284 +/- 9.2 days, and nulliparous represented 31.2% of the study population. At time 0, Bishop score was less than 4 in 74% (57/77) of the subjects, mean cervical length was 28.6 +/- 5.8 mm, mean NOx concentration was 208.6 +/- 103.8 microM/mL; 6 hours later, at T6, the mean cervical length decreased to 19.5 +/- 8.8 mm, and the mean NOx concentration increased up to 316.7 +/- 240.9 microM/mL. Data were unaffected by parity or by regular uterine contraction patterns. A statistically significant positive correlation was found between changes in cervical NOx levels and Bishop score modification (P < .01; r = .494), as well as between the modification of NO metabolites concentration and cervical shortening (P < .01; r = .307). CONCLUSIONS: Prostaglandin (PG)-induced cervical ripening is associated with local NO release. NO plays an active role in cervical remodeling since it positively correlates with both cervical shortening and Bishop score increase. NO oxide and PG are the two pathways that, cross activating each other, trigger the cascade of events responsible of cervical ripening.

[Migraine in SLE: role of antiphospholipid antibodies and Raynaud's phenomenon]. / Emicrania nel LES: ruolo del fenomeno di Raynaud e degli anticorpi antifospolipidi.

OBJECTIVES: To determine the role of antiphospholipid antibodies (aPL) and of Raynaud's phenomenon (RP) in the development of migraine in patients with systemic lupus erythematosus (SLE). METHODS: 50 unselected SLE patients and 20 rheumatoid arthritis (RA) controls underwent an interview to define the presence of migraine according to the guidelines of the International Headache Society (1988). Serological tests for aPL were performed in all patients. SLE patients were divided according to positivity for RP and/or aPL into 4 subsets: R-/aPL-, R-/aPL+, R+/aPL- and R+/aPL+. Data were analysed using Fisher's exact test, Chi-square test and U Mann-Whitney test. RESULTS: SLE and RA patients were similar for demographic and clinical features; aPL positivity was found in a greater proportion of SLE patients versus RA controls (68% vs 25%, p=0.0036). 31 of the 50 lupic patients (62%) and 7 of the 20 RA controls (35%) suffered from migraine (OR=3, CI:1-8.9). Among SLE and RA patients, migraine was associated with aPL positivity (p=0.027 and p=0.019). Analysing the combined effect of aPL and RP on migraine, in R+/aPL+ patients we detected an higher frequency of migraine (85.7%) with respect to the patients negative for these two features (27%, p=0.0051, OR=16, CI:2.2-118) and to the patients positive only for aPL (65%, p=0.0031, OR=6.2, CI:1.2-32). CONCLUSIONS: Migraine in SLE and RA associates with aPL positivity. The simultaneous presence of RP increases by 2,5 times the probability of having migraine, suggesting that cerebral vasospasm might be more common in patients with peripheral vasospasm, given the presence of aPL.

Induction of labor in women with oligohydramnios.

OBJECTIVE: To prospectively evaluate the outcome of labor induction in women with oligohydramnios at term. METHODS: This was a prospective case-control study which included 120 consecutive patients with Amniotic Fluid Index (AFI) < or =5 undergoing labor induction. One hundred and sixteen patients with normal amniotic fluid matched for gestational age (+/- 3 days) and Bishop-score served as controls. Inclusion criteria were: requirement of labor induction, singleton pregnancy, nulliparity, Bishop score <5, gestational age > or =266. Preinduction treatment included the use of up to 3 successive doses of dinoprostone intracervical gel (0.5 mg). Vaginal dinoprostone (2 mg) and/or oxytocin were then applied to induction labor, if necessary. RESULTS: The rate of cesarean section in AFI < or = 5 group (38.3%) was not significantly different to that in control group (34.2%). The interval from induction to vaginal delivery was not significantly different for AFI < or =5 group (1499 +/- 895 min.) and control group (1398 +/- 852 min.). The changes in Bishop score evaluated at 6th and 12th hour after dinoprostone were not significantly different in control and AFI< or =5 group. More women in the latter group (11.7% vs 3.3%, Chi Square:4.86, p = 0.027) required the use of drugs in order to manage tachysystole/hyperstimulation allowing a OR = 3.83 (95%C.I. = 1.13-14.27). The length of stay at hospital was 4.2 +/- 1.8 days for AFI < or =5 group and 4.3 +/- 1.3 for control group. CONCLUSIONS: Oligohydranmios at term did not influence the outcome of induction of labour in nulliparous women with unfavorable cervix.

Comparison of two preparations of dinoprostone for pre-induction of labour in nulliparous women with very unfavourable cervical condition: a randomised clinical trial.

The aim of this study was to compare the clinical effects of preinduction cervical ripening by using two ways of dinoprostone administration. In a prospective, open-label trial, 144 consecutive nulliparous women with a Bishop score <4 who required induction of labour at term were randomised to receive dinoprostone via either a vaginal insert (10 mg over 12 h) or a cervical gel (0.5 mg, twice in 12 h). If labour did not start by 24 h after this preinduction, patients received 2 mg vaginal dinoprostone gel followed 6 h later by oxytocin infusion. The main outcome measure was the rate of caesarean sections (CS). Secondary measures were: changes in Bishop score at 6 h and 12 h, delivery within 12 h and 24 h, need for oxytocin for induction, failure of induction (delivery after >48 h), need for pharmacological interventions to manage tachysystole/hyperstimulation, length of stay in hospital. The CS rate was lower in the vaginal insert group (22.9%) than in the cervical gel group (34.3%), though the difference did not reach statistical significant difference (P = 0.13). The indications for CS overlapped between the groups. The rate of vaginal delivery within 12 h and 24 h was similar, as was the rate of failure of induction. More women in the gel group (41.4% versus 24.3%) required the use of oxytocin (OR = 2.21; 95% CI = 1.07-4.55). Tachysystole or hyperstimulation in the vaginal insert group (7) was twice that with cervical gel (4). Four women in the vaginal insert group and three in the cervical gel group reported infectious complications. A long stay in hospital (>4 days) was less frequent with vaginal inserts (21.4 versus 38.6%; OR = 0.43, 95% CI = 0.19-0.97). The more challenging preinductions of labour at term are associated with increased obstetric interventions such as a high CS rate and a more frequent requirement for oxytocin inductions. In terms of success and failure, vaginal inserts releasing dinoprostone do not differ from dinoprostone given by the traditional cervical route. However, the use of vaginal inserts reduces the need for obstetric interventions and allows shorter periods in hospital.

Changes in the cervical competence in preterm labour.

Cervical competence is a key function in normal and abnormal labour. Remodelling of the cervical structure, by reorientation and changes in the integrity of collagen fibres by an alteration in the content of water, proteoglycans and hyaluronic acid, takes place before parturition. Such morphological changes have been associated with the activation of several biochemical pathways, sharing those of an apyretic, proinflammatory reaction, including the inducible isoform of the nitric oxide synthase (NOS). Nitric oxide (NO) is believed to be the final mediator in the mechanisms that allow ripening of the cervix. A reduction of NO activity in the uterus, together with its activation in the cervix, is hypothesised to be a facilitating factor in human parturition. The local application of NO donors in both animals and humans induces ultrastructural changes similar to those occurring during physiological cervical maturation. NO donors have proven to be clinically effective in facilitating first trimester dilation and curettage. Preliminary data also suggest that in women presenting with threatening preterm labour, there is increased activity of NO in the cervix, which is associated with shortening. A complex interaction between cytokines, prostaglandins (PGs) and NO is the key biochemical pathway accounting for the preterm ripening of the cervix.