Delivery of the second twin: influence of presentation on neonatal outcome, a case controlled study.

BACKGROUND: Spontaneous vaginal twin delivery after 32nd week of gestation is safe when first twin presenting cephalic. Aim of this study is to identify obstetric factors influencing the condition of second twin and to verify whether non-cephalic presentation and vaginal breech delivery of the second twin is safe. METHODS: This is a retrospective case controlled cohort study of 717 uncomplicated twin deliveries ≥32 + 0 weeks of gestation from 2005 to 2014 in two tertiary perinatal centers. Obstetric parameters were evaluated in three groups with descriptive, univariate logistic regression analysis for perinatal outcome of second twins. RESULTS: The three groups included twins delivered by elective cesarean section ECS (n = 277, 38.6%), by unplanned cesarean section UPC (n = 233, 32.5%) and vaginally (n = 207, 28.9%). Serious adverse fetal outcome is rare and we found no differences between the groups. Second twins after ECS had significant better umbilical artery UA pH (p < 0.001) and better Apgar compared to UPC (p = 0.002). Variables for a fetal population "at risk" for adverse neonatal outcome after vaginal delivery (UA pH < 7.20, Apgar 5´ < 9) were associated with higher gestational age (p = 0.001), longer twin-twin interval (p = 0.05) and vacuum extraction of twin A (p = 0.04). Non-cephalic presentation of second twins was not associated (UA pH < 7.20 OR 1.97, CI 95% 0.93-4.22, p = 0.07, Apgar 5´ < 9 OR 1.63, CI 95% 0.70-3.77, p = 0.25, Transfer to neonatal intermediate care unit p = 0.48). Twenty-one second twins (2,9%) were delivered by cesarean section following vaginal delivery of the first twin. Even though non-cephalic presentation was overrepresented in this subgroup, outcome variables were not significantly different compared to cephalic presentation. CONCLUSIONS: Even though elective cesarean means reduced stress for second twins this seems not to be clinically relevant. Non-cephalic presentation of the second twin does not significantly influence the perinatal outcome of the second twin but might be a risk factor for vaginal-cesarean birth.

Carboplatin and nonpegylated liposomal doxorubicin in primary advanced or recurrent endometrial cancer: a phase 2 trial conducted by AGO Austria.

OBJECTIVE: Recurrent/advanced endometrial carcinoma carries a poor prognosis. Chemotherapy usually consists of cisplatin/doxorubicin and paclitaxel or the doublet of carboplatin and paclitaxel.We report on final results of the Austrian phase 2 AGO trial of nonpegylated doxorubicin citrate and carboplatin in 39 patients with primary advanced or relapsed endometrial cancer. The main primary end point is response rate, and the main secondary end point is feasibility. METHODS: Thirty-nine patients received 60 mg/m nonpegylated doxorubicin citrate and carboplatin (area under the curve, 5) every 3 weeks for 6 to 9 cycles or until progression. Best response during therapy, progression-free survival, and the toxicity profile were recorded. RESULTS: Thirteen patients (33%) had primary advanced disease, and 26 patients (67%) had recurrent disease. Seventy-five percent of the tumors were adenocarcinomas, 15% were serous carcinomas, and 5% were clear cell and mixed müllerian carcinomas. We observed 1 complete response (3%) and 16 partial responses (41%) in the intention-to-treat population. The median progression-free survival was 7.2 months, and the median overall survival was 14.7 months. Overall, 177 cycles were administered; the mean number of cycles per patient was 4.5. Ten percent of patients received 9 cycles of chemotherapy, and 44% of patients received 6 cycles of chemotherapy. Grade 3/4 neutropenia occurred in 17%, grade 3/4 anemia in 5%, and grade 3/4 thrombopenia in 12% of the cycles. In 6% of the cycles, febrile neutropenia was noticed. Grade 3/4 nausea was seen in 5% of cycles. One patient (3%) experienced cardiac toxicity and had a reduction in the left ventricular ejection fraction to below 50%. CONCLUSIONS: The reported combination demonstrates considerable activity and should be evaluated further.

Incidence of Medication-Related Osteonecrosis of the Jaw in Patients With Breast Cancer During a 20-Year Follow-Up: A Population-Based Multicenter Retrospective Study.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is one of the most important toxicities of antiresorptive therapy, which is standard practice for patients with breast cancer and bone metastases. However, the population-based incidence of MRONJ is not well established. We therefore performed a retrospective multicenter study to assess the incidence for a whole Austrian federal state (Tyrol). MATERIALS AND METHODS: This retrospective multicenter study was conducted between 2000 and 2020 at all nine breast centers across Tyrol, Austria. Using the cancer registry, the total Tyrolean population was screened for all patients with breast cancer. All patients with breast cancer and bone metastases receiving antiresorptive therapy were finally included in the study. RESULTS: From 8,860 patients initially screened, 639 individuals were eligible and included in our study. Patients received antiresorptive therapy once per month without de-escalation of therapy. MRONJ was diagnosed in 56 (8.8%, 95% CI, 6.6 to 11.0) patients. The incidence of MRONJ was 11.6% (95% CI, 8.0 to 15.3) in individuals treated with denosumab only, 2.8% (95% CI, 0.7 to 4.8) in those treated with bisphosphonates only, and 16.3% (95% CI, 8.8 to 23.9) in the group receiving bisphosphonates followed by denosumab. Individuals developed MRONJ significantly earlier when treated with denosumab. Time to MRONJ after treatment initiation was 4.6 years for individuals treated with denosumab only, 5.1 years for individuals treated with bisphosphonates only, and 8.4 years for individuals treated with both consecutively. CONCLUSION: MRONJ incidence in breast cancer patients with bone metastases was found to be considerably higher, especially for patients receiving denosumab, when compared with available data in the literature. Additionally, patients treated with denosumab developed MRONJ significantly earlier.

Diagnostic accuracy of guided cervical biopsies: a prospective multicenter study comparing the histopathology of simultaneous biopsy and cone specimen.

OBJECTIVE: We sought to determine the validity of colposcopically directed cervical biopsies as a diagnostic test to define the degree of cervical intraepithelial neoplasia (CIN). STUDY DESIGN: In a prospective multicenter trial, patients undergoing excisional procedures of the transformation zone additionally had colposcopy and up to 3 guided cervical biopsies in a single procedure. Cervical biopsies were regarded as a diagnostic test to detect high-grade lesions (CIN 2,3), with the cone specimen as reference standard. RESULTS: In all, 488 biopsies were performed in 244 cases, with 2 biopsies done in 192 cases. Cervical biopsies underestimated the severity of lesions in 46.7% of cases. Sensitivity, specificity, and positive and negative predictive values were 66.2% (95% confidence interval [CI], 59.4-72.3), 95.0% (95% CI, 83.5-98.6), 98.5% (95% CI, 94.8-99.6), and 35.5% (95% CI, 27.1-44.9), respectively. CONCLUSION: Our data suggest that cytologically suspected high-grade lesions (CIN 2,3) can be confirmed by biopsy in many cases, but they cannot be excluded.

Contralateral prophylactic mastectomy in women with breast cancer without a family history or genetic predisposition : Consensus statement from the Austrian Gynecologic Oncology Working Group of the Austrian Society of Obstetrics and Gynecology.

The working group recommends against contralateral prophylactic mastectomy (CPM) in women with breast cancer without a family history or genetic predisposition with unilateral breast cancer. This is based on the low risk of developing contralateral breast cancer, the lack of a survival benefit, the increased risk of surgical complications, and the lack of benefit on quality of life.

Prognostic significance of TPA versus SCC-Ag, CEA and neopterin in carcinoma of the uterine cervix.

INTRODUCTION: Prognostic significance of squamous cell carcinoma antigen (SCC-Ag), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA) and neopterin in cervical cancer patients was compared. MATERIALS AND METHODS: Pretreatment concentrations were determined in 138 women. RESULTS: Median age was 52 years, 85% squamous cell carcinomas, 15% adeno- or adenosquamous carcinomas were seen. In 36% Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I, 24% stage II, 32% stage III and 8% stage IV was diagnosed. TPA was elevated in 22%, SCC in 68%, CEA in 42% and neopterin in 29%. These patients showed significantly worse overall survival in univariate analysis (p<0.001). TPA remained as independent prognostic factor in multivariate analysis. CONCLUSIONS: Elevation of TPA was associated with worse overall survival.

Erythropoetin beta twice weekly versus standard therapy in patients with gynaecological malignancies--a randomised Austrian AGO trial.

BACKGROUND: The influence of two regimens of erythropoetin beta on haemoglobin level, quality of life (QoL) and side-effects in patients with gynaecological malignancies was assessed. PATIENTS AND METHODS: A total of 119 patients during chemotherapy were randomised to either standard therapy with 10,000 IU erythropoetin beta three times a week (group A) or 20,000 IU twice a week (group B). Haemoglobin level and QoL were measured. Characteristics of the study population were analysed with descriptive statistical methods. Analysis of variance for repeated measurements was performed with haemoglobin level as dependent variable, and time and study arms as factors. RESULTS: The rise in haemoglobin levels and QoL improvement were significant, without any difference between study arms. Adverse events were similar, except significantly more thromboembolic events in group B (0 vs. 8 events; p = 0.003). CONCLUSION: Our results show similar improvements in haemoglobin level and QoL, but raise the question whether less frequent dosing regimes may result in increased rates of thromboembolic events.

Enhancement of cholesteryl ester transfer in plasma by hormone-replacement therapy.

To study possible mechanisms for the suggested protective effect of hormone-replacement therapy (HRT) with respect to cardiovascular disease we investigated lipoprotein parameters, mass and activity of lipoprotein-metabolizing enzymes, magnitude of postprandial lipemia, and vascular endothelial function in 13 postmenopausal women. All patients were examined before and 3 months after implementation of HRT with estrogen alone (group A, n = 6) or estrogen plus gestagen (group B, n = 7). HRT (groups A and B) resulted in enhanced total transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins (56% +/- 11.45% v 50.82% +/- 13.68%, P <.05) and increased apoA-I plasma concentration (171 +/- 30 v 147 +/- 22 mg/dL, P <.05). Fasting triglycerides (TG) were increased (134 +/- 40 v 115 +/- 39 mg/dL, P <.05). In group A patients the magnitude of postprandial lipemia increased significantly (1,737 +/- 756 v 1,475 +/- 930 mg TG/dL plasma/8 h, P <.05) without any change in lipoprotein lipase (LPL) activity, but with a concomitant decrease in low-density lipoprotein (LDL) size. In both groups flow-mediated dilation (FMD) reflecting vascular endothelial function was not influenced, suggesting that HRT may not directly affect vascular function but rather alters lipoprotein metabolism. The increase of apoA-I was not accompanied by an equivalent rise of HDL cholesterol. Based on the present data this finding can be readily explained by an increase in CE transfer from HDL to TG-rich lipoproteins, which is not due to increased cholesteryl ester transfer protein (CETP) plasma levels, but rather reflects an increase in fasting and postprandial TG. In conclusion, the net effect of accelerated CE transfer due to HRT depends on the balance of proatherogenic aspects, like the generation of small dense LDL, and antiatherogenic aspects, like the stimulation of reverse cholesterol transport.

Importance of erythropoetin receptor expression in tumour tissue for the clinical course of breast cancer.

BACKGROUND: Adverse outcomes in breast cancer patients treated with recombinant human erythropoietin (rhEpo) have been linked to the expression of Epo-receptors (EpoR) in cancer cells, although limited data on the clinical significance of these observations are available. PATIENTS AND METHODS: Tissue samples from 107 patients with breast cancer who did not receive rhEpo and from 12 patients with benign lesions were retrospectively analysed for EpoR expression by RT-PCR and Western blot, and the results were correlated to clinical and demographic data. RESULTS: While EpoR levels were not linked to anaemia or inflammation, they were positively associated with progesterone and oestrogen receptor status. Patients with increased EpoR-mRNA expression had a higher local cancer recurrence rate (p=0.021), however, no significant difference in overall survival was observed. CONCLUSION: Since EpoR expression is associated with hormone receptor positivity and decreased locoregional disease control, this parameter characterises a specific cancer phenotype rather than being a negative predictor itself.

Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse.

PURPOSE: This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC). PATIENTS AND METHODS: Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m(2)) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m(2)) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival. RESULTS: Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm. CONCLUSION: To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.

Type-specific antiviral antibodies to genital human papillomavirus types in mothers and newborns.

Type-specific antibodies to human papillomaviruses (HPVs) can be detected in most infected adult patients, and they have virus-neutralizing properties. However, there is a dearth of information on the seroprevalence of maternal and neonatal antibodies to HPV capsid antigens. Sera from 104 mothers, their newborns, and 3 twin pregnancies were analyzed by an enzyme-linked immunosorbent assay (ELISA) for the presence of specific IgG, IgM, and IgA antibodies to virus-like particles of HPV-6, -11, -16, -18, and -31. Maternal IgG positivity rates to HPV types 6, 11, 16, 18, and 31 were 23.1%, 2.9%, 8.7%, 5.8%, and 9.6%, respectively. Neonatal rates did not differ significantly, and individual IgG ELISA values of mothers and their infants and all paired twins showed a very high correlation. In contrast, nearly all IgM and IgA individual values in newborns were designated negative, whereas mothers' positivity rates ranged as high as 19.2%. Infants showed no HPV-related lesions at birth or at 4-year follow-up. Seven of 8 tested children lost IgG HPV antibodies in a follow-up examination. Similar anti-HPV IgG seropositivity in mothers and newborns and a lack of neonatal IgA and IgM together with twin and follow-up results indicate that neonatal IgG is not a sign of intrauterine HPV infection but, rather, maternofetal antibody transmission.