Tranexamic acid versus oxytocin prophylaxis in reducing post-partum blood loss, in low-risk pregnant women: TRANOXY STUDY, a phase III randomized clinical trial.

Background: To assess the equivalence of tranexamic acid (TRAN) versus synthetic oxytocin (OXY) in reducing post-partum blood loss, in full-term patients (37-42 weeks), at low risk of post-partum hemorrhage, with vaginal childbirth. Methods: Phase III, randomized (1:1), open-label, longitudinal, multi-center, prospective clinical trial (Prot. n 63209, ClinicalTrials.gov Identifier: NCT02775773). From January 7, 2020, to June 30, 2023, a total of 256 women were enrolled at two general urban community hospitals in Italy, serving a multi-ethnic patient population with National Health Insurance. The primary outcome was to explore a potential equivalence between the two treatments (OXY and TRAN) in preventing total blood loss. Therefore, we randomized 231 women into two groups: Group A (OXY), 127 women who were administered 10UI intramuscularly within 5 min from childbirth; Group B (TRAN), 104 women to whom 1-g slow intravenous infusion was administered within 5 min from childbirth. Findings: At the time of delivery, mean blood loss for OXY group versus TRAN group was 269.12 mL versus 263.88 mL, respectively, with equivalence between the two groups. Similarly, there was equivalence in total blood loss between the OXY and the TRAN group (397.66 mL versus 405.64 mL, respectively. No statistical differences between Hb levels at admission and discharge in the two groups were reported. No difference was found in terms of additional uterotonic and surgical therapies between the two groups of patients. Neither group showed thrombotic complications at check-up performed after 7 days or after a questionnaire regarding adverse effects, subjected after 40 days. Interpretation: The study shows the equivalence of tranexamic acid versus synthetic oxytocin in post-partum blood loss prophylaxis in term patients at low risk of PPH with vaginal childbirth. The safety profiles of OXY and TRAN were similar. Funding: None.

The fertility-sparing treatment in patients with endometrial atypical hyperplasia and early endometrial cancer: a debated therapeutic option.

Fertility-sparing treatment may represent a realist option for accurately selected young patients with endometrial atypical hyperplasia or well differentiated, early endometrial cancer. Oral progestins, and especially medroxyprogesterone acetate (MPA) and megestrol acetate with different doses and schedules, represent the most commonly used hormone agents in this clinical setting. Approximately three fourths of the women achieve a histologically documented complete response, with an mean response time of 12 weeks, but about one third of these subsequently developed a recurrence after a mean time of 20 months. The expression of receptor for progesterone receptor (PR), PTEN gene, DNA mismatch repair gene MLH1 and phospho-AKT on tissue specimens may be useful for selecting patients fit for a conservative management. Several successful pregnancies have occurred after a fertility-sparing treatment of endometrial atypical hyperplasia or endometrial cancer, more frequently with assisted reproductive technologies. The implementation of in vitro fertilisation techniques not only increases the chance of conception, but it may also decrease the interval to conception. The opportunity of a demolitive surgery after delivery or after childbearing being no longer required is a still debated issue. Large multicenter trials are strongly warranted to better define the selection criteria for a conservative treatment, endocrine regimen of choice, the optimal dosing, the duration of treatment and follow-up protocols. In any case, the patient should be accurately informed about the relatively high recurrence rates after complete response to hormone treatment and expectations for pregnancy.

Maternal anemia effects during pregnancy on male and female fetuses: are there any differences?

OBJECTIVE: Sideropenic anemia is a common pregnancy disorder. The relationship between anemia and adverse pregnancy outcome are contradictory, and it is related to the severity of the hemoglobin deficit. The aim of the study was to evaluate the relationship between maternal mild anemia at third trimester of pregnancy, fetal birth weight and fetal gender. STUDY DESIGN: A retrospective study including 1131 single physiological term pregnancies was conducted. According to maternal Hb levels during the third trimester, pregnant women enrolled were divided in two groups: Group A (n = 156) with Hb ≤ 11 g/dl and Group B (n = 975) with Hb ≥ 11,1 g/dl. RESULTS: Maternal characteristics, gestational age at delivery, Apgar score and post-partum hemorrhage were similar between groups. However, when neonatal sex was considerate, female newborns of anemic women had a higher birth weight (p = 0.01). Moreover, anemic women showed a significantly higher rate of emergency cesarean section (p = 0.006), in particular when the newborn was a male (p= 0.03). CONCLUSION: Maternal mild anemia in third trimester of pregnancy correlates with fetal birth weight, influencing fetal growth and delivery outcome on the basis of fetal gender. Even though the reason of this phenomenon is still unknown, these new data may represent a novel parameter to add significant prognostic information in relation to maternal mild anemia and neonatal outcome.

Clear cell carcinoma of the endometrium: a biological and clinical enigma.

Clear cell carcinoma accounts for only 1 to 5.5% of all endometrial carcinomas, and it is often associated with an aggressive clinical behavior and a poor outcome. According to the FIGO Annual Report 2006, 5-year overall survival was 62.5% for patients with this histological type compared with 83.2% for those with endometrioid carcinoma of the endometrium. In contrast to endometrioid carcinoma and uterine papillary serous carcinoma (UPSC), the molecular pathways involved in the development of clear cell carcinoma are still unclear. Literature data on the pattern of failures and the optimal treatment modalities of the clear cell carcinoma are not well defined, largely because most papers have assessed clear cell carcinoma and UPSC together because of their rarity. Patients with clear cell carcinoma often experience relapse in the pelvis, in para-aortic nodes and at distant sites, whereas they do not seem to have a high propensity to fail in the abdomen. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with comprehensive surgical staging is the standard surgical treatment of patients with clear cell carcinoma of the endometrium, whereas pelvic irradiation, with or without brachytherapy and/or para-aortic irradiation, whole-abdomen irradiation, and chemotherapy have been widely employed as postoperative therapy. However, no commonly accepted guidelines are currently available for the management of these patients. An adequate molecular characterization of clear cell carcinoma of the endometrium is strongly warranted in order to identify new biological prognostic variables of the disease and to develop novel molecular targeted therapies.

The perioperative management of patients with gynaecological cancer undergoing major surgery: A debated clinical challenge.

Major extensive surgery still represents a cornstone of therapy of gynaecological cancer, and the adoption of implemented clinical guidelines for perioperative management can significantly decrease patient morbidity and mortality and reduce hospital stay. The overall risk of deep venous thrombosis in patients undergoing gynaecological surgery ranges from 7% to 45%, and fatal pulmonary embolism occurs in approximately 1% of these women. A meta-analyses of randomised trials showed a significant decrease in deep venous thrombosis in women receiving unfractioned heparin [UFH] compared with controls, and revealed no significant difference in deep venous thrombosis and pulmonary embolism between patients who received UFH and those who received low-molecular weight heparin [LMWH]. Potential advantages favouring LMWH over UFH include once-daily versus repeated daily injections and a lower risk of heparin-induced thrombocytopenia. All patients undergoing major surgical operations should receive LMWH that should be started preoperatively and then given for 7-10 days at least and prolonged for up to 4 weeks in high-risk cases. Antithrombotic mechanical methods can be added to pharmacological agents, but should not been used alone. Cephalosporins and amoxicillin-clavulanic acid have been widely used in gynaecological surgery prophylaxis. Both amoxicillin-clavulanic acid and cefazolin have good in vitro activity against the microbes more frequently involved in postoperative infections, such as Gram-negative bacilli, but amoxicillin-clavulanic acid is more effective against anaerobes. A single dose of antibiotics has been shown to be as effective as multiple doses in many trials that have compared a single-dose regimen with a multiple-dose regimen. Amoxicillin-clavulanic acid prophylaxis at the induction of anaesthesia can be suggested for gynaecological cancer patients undergoing major gynaecological surgery with or without colorectal resection. An additional antibiotic dose is recommended for prolonged operations or when intraoperative blood loss is important. Cephalosporins can be administered to women with a history of penicillin allergy not manifested by an immediate hypersensitivity reaction, whereas tigecyclin should be reserved to patients with a prior anaphylactic reaction to beta-lactams. Recent meta-analyses of randomised trials on patients undergoing elective colorectal surgery found more anastomotic leakages in patients who had preoperative mechanical bowel preparation with oral administration of different solutions than in those who had not, whereas there were no significant differences between the two arms as for wound infections, other septic complications, and non-septic complications. Therefore, preoperative mechanical bowel cleansing is not warranted for gynaecological cancer patients scheduled for surgery that may involve colon-rectum. After major abdominal gynaecological surgery, early oral feeding (within the first 24h regardless of the resolution of postoperative ileus) appears to be associated with increased nausea, shorter time to the presence of bowel sound, shorter time to first solid diet, and a trend toward shorter hospital stay when compared with delayed feeding. Since early oral feeding is safe but associated with increased nausea, the decision whether to adopt this postoperative regimen should be individualised. Decision making processes about thromboprophylaxis, antibiotic prophylaxis, bowel preparation for surgery that may involve colon-rectum, and timing of postoperative oral feeding will become more and more relevant for improved safety and quality of life of women with gynaecological cancer.