Risk factor analysis in women who underwent trial of labor after cesarean section: a multicenter study in Germany

Objective: Rising caesarean delivery (CD) rates throughout the world are accompanied with high rates of severe maternal complications. The aim of the present study was to analyze the outcome of trial of labor after caesarean section (TOLAC) in a Western population and identify factors associated with the success of vaginal birth after caesarean section (VBAC). Material and Methods: A retrospective study was performed at two large obstetric departments in Germany from 2008 to 2018. Women with singleton pregnancies, a history of only one previous CD with a low transverse incision, a viable fetus in cephalic presentation, and gestational age >32 weeks were included in the study. The characteristics and outcome of successful VBAC and failed TOLAC were compared. A subgroup analysis addressed gestational age, interpregnancy interval, fetal macrosomia, body mass index, and maternal age. Results: Of 1,546 patients, 62.3% achieved VBAC while 37.7% had a secondary CD. Independent factors associated with the success of TOLAC were a history of vaginal birth in previous pregnancies (p<0.001) and the use of oxytocin (p<0.001), whereas preterm birth between gestational week 32 and 37 signified a higher risk of failed TOLAC (p=0.04). The success of VBAC did not differ significantly for patients older than 40 years of age, those with a shorter interpregnancy interval than 12 months, and fetal macrosomia with birth weight exceeding 4000 grams. Maternal and neonatal outcomes were poorer in women with failed TOLAC. Conclusion: Nearly two thirds of women with a history of CD achieve VBAC in Germany. Previous vaginal birth and the augmentation of labor with oxytocin are positively associated with the achievement of VBAC and no major perinatal complications. The decision to have a TOLAC should be encouraged in the majority of patients. Further studies are needed to evaluate the feasibility of TOLAC in preterm delivery.

Effect of tumor morcellation in patients with early uterine sarcoma: a multicenter study in Germany

Objective: The use of power morcellation at laparoscopy may worsen survival rates for patients with malignancy. The aim of the present study was to report the outcome of patients with early-stage uterine sarcoma after morcellation or total en-bloc resection, and evaluate potential signs of sarcoma preoperatively. Material and Methods: This multicenter retrospective study consisted of patients, who underwent surgery for FIGO-stage-1 uterine sarcoma. Twenty-four patients were divided into a non-morcellation group and a morcellation group. Clinical records and the outcomes of patients, including one-, three- and five-year survival rates were reviewed. Preoperative characteristics of patients with sarcoma were compared to those of a control group with uterine myoma (1:4 ratio), matched by age and type of operation. Results: Obesity was an independent risk factor for uterine myoma. Tumor growth, solitary growth, largest-diameter lesion >8.0 cm, and anechoic areas suggesting necrosis and increased vascularization were significantly more common in the sarcoma group. A large tumor diameter was significantly associated with mortality. Patients in the non-morcellation group had a slightly lower disease-free survival, but poorer overall survival (OS) rates compared to patients in the morcellation group, but neither difference was statistically significant. Patients in the non-morcellation group, who had undergone a re-exploration experienced late recurrence, but no upstaging was evident after the operation. Conclusion: Preoperative ultrasound characteristics could be useful to distinguish sarcoma from leiomyoma of uterus. Morcellation of a sarcoma may increase abdominal and pelvic recurrence rates, but may not be associated with OS in patients with FIGO-stage-1 disease.

Papillary squamotransitional cell carcinoma of the uterine cervix: a case report and review of the literature.

BACKGROUND: Papillary squamotransitional cell carcinoma of the uterine cervix is a rare neoplasm, a subtype of transitional cervical carcinoma that appears to be a variation of squamous cervical carcinoma. It has a disposition toward metastasis at an advanced stage and local recurrence. Owing to the difficulty of illustrating the invasion histologically, misdiagnosis is likely to affect the patient's prognosis. CASE PRESENTATION: We present a case report of an 81-year-old Caucasian patient with squamotransitional cell carcinoma with unusual clinical behavior that was primarily thought to be ovarian cancer. According to the clinical examination and radiologic imaging, the patient had no vaginal bleeding and a normal cervix. Nevertheless, the tumor was already metastasized at the retroperitoneal tissue and at the right ovary. Computed tomography-guided biopsy of the right adnexa gave no further clarification. Although the tumor resembled urothelial cancer, this diagnosis was dismissed because of the results of immunohistochemistry analysis with CK7+, CK5+, and CK20-. Because of the differential diagnosis of ovarian cancer, we decided in favor of an exploratory surgical approach. Hysterectomy with bilateral adnexectomy, extensive retroperitoneal tumor debulking, and infragastric omentectomy was performed by laparotomy. Histopathology revealed a squamotransitional cervical cancer as the primary tumor with a tumor stage of pT3b, pN1 (1/2), V0, RX, G2, corresponding to International Federation of Gynecology and Obstetrics stage IIIB. CONCLUSIONS: As far as we are aware, this is the first report of papillary squamotransitional cell carcinoma of the uterine cervix metastatic to the ovary without vaginal bleeding and with a clinically and radiologically unsuspicious cervix. Physicians should always contemplate papillary squamotransitional cell carcinoma of the uterine cervix in unclear cases with ovarian metastasis, especially if the histology indicates a transitional cancer (CK7+ and CK20-), before proceeding with treatment. More cases are needed to illuminate the clinical characteristics and categorization of papillary squamotransitional cell carcinoma of the uterine cervix.

Misoprostol for pre-term labor induction in the second trimester: Role of medical history and clinical parameters for prediction of time to delivery.

OBJECTIVE: Serious fetal malformations and/or chromosome aberrations detected by modern diagnostic tools in early pregnancy require discussions on induced abortion with pregnant women. Competent counseling includes prediction of the time needed for the whole abortion process. In an attempt to refine our predictions, we evaluated the impact of 11 medical history and clinical variables on time to delivery. MATERIAL AND METHODS: We performed a retrospective chart analysis on 79 women submitted for pre-term abortion because of fetal anomalies. Abortion was induced by vaginal application of misoprostol (prostaglandine E1, Cytotec™, Pfizer, New York, USA). We investigated 11 medical history and clinical variables for their impact on the percentage of women delivering within 24 hours (primary endpoint) and on the mean induction-delivery time interval (secondary endpoint). RESULTS: Fifty-three percent (42/79) of women delivered within 24 hours; 83.6% (66/79) delivered within 48 hours. A total of 83.3% of women with a history of late abortion delivered within 24 hours, whereas 50.7% without this history did. Mean induction-delivery time interval was 12.3 hours versus 35.5 hours, respectively. For history of early abortion, the figures were 65.2% versus 48.2% for delivery within 24 hours and 15.6 hours versus 32.5 hours for mean induction-delivery time interval. Current weight of fetus >500 g, weight of last previous newborn of ≤3500 g, previous pregnancies, premature rupture of membranes, and an elevated CRP of >0.5 mg/dL also cut time to delivery. Surprisingly, maternal and gestational age had no remarkable or consistent impact on the mean induction-delivery time interval. None of the differences reached statistical significance. Eighty-three percent of women needed 1000 µg or less for successful delivery. CONCLUSION: Neither variables of medical history nor specific clinical variables allow for precise prediction of time to delivery in the second trimester. Certain parameters, however, show a trend to reduce the induction-delivery time interval. Our results might serve as initial guidance for patient counseling.

Migration and maternity: insights of context, health policy, and research evidence on experiences and outcomes from a three country preliminary study across Germany, Canada, and the United kingdom.

A group from Germany, Canada, and the United Kingdom undertook country-specific scoping reviews and stakeholder consultations before joining to holistically compare migration and maternity in all three countries. We examined four interlinking dimensions to understand how international migrant/minority maternal health might be improved upon using transnational research: (a) wider sociopolitical context, (b) health policy arena, (c) constellation, outcomes, and experiences of maternity services, and (d) existing research contexts. There was clear evidence that the constellation and delivery of services may undermine good experiences and outcomes. Interventions to improve access and quality of care remain small scale, short term, and lacking in rigorous evaluation.

Axillary ultrasound for breast cancer staging: an attempt to identify clinical/histopathological factors impacting diagnostic performance.

AIM: To assess the diagnostic value of pre-surgery axillary ultrasound for nodal staging in patients with primary breast cancer and to identify clinical/histopathological factors impacting diagnostic performance. STUDY DESIGN: Single-center, retrospective chart analysis. We assessed sensitivity, specificity, and positive and negative predictive value of clinical examination as well as axillary ultrasound vs. clinical examination alone. The histopathological results were the standard of truth. In addition, we analyzed clinical and histopathological factors regarding their potential to impact sensitivity and specificity. RESULTS: We enrolled a total of 172 women in the study. Sensitivity of clinical examination plus ultrasound was significantly higher than for clinical examination alone (58% vs. 31.6%). Specificity and positive predictive value were similar while the negative predictive value increased from 63.4% to 73% when additionally applying ultrasound. Sensitivity and specificity of axillary ultrasound were impacted by tumor size (P = 0.2/0.04), suspicious axillary palpation (P < 0.01/<0.01), number of affected lymph nodes (P < 0.01/-) and distant metastases (P = 0.04/<0.01). All other factors had no impact. CONCLUSION: Since pre-surgery axillary nodal staging is currently used to determine disease management, axillary ultrasound is a useful add-on tool in the diagnostic armamentarium for breast cancer patients. Tumor size, suspicious axillary palpation, number of affected lymph nodes and distant metastases increase diagnostic performance of this diagnostic modality.

The metabolic effects of drugs used for the treatment of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. It is characterized by menstrual disorders, hyperandrogenism (clinical and/or biochemical) and ultrasonographic features. It is well known that PCOS has unfavourable effects on carbohydrate metabolism, the parameters of cardiovascular disease and lipid profile. Mode of treatment is mainly guided by the main complaint of the patient. A lot of medicines have been used for many years to treat these women. For that reason the recognition the effects of these drugs on the metabolic risk profile is important. The aim of this review was to evaluate the effects of these drugs on metabolic parameters in women with PCOS.

Axillary dissection in primary breast cancer: variations of the surgical technique and influence on morbidity.

Lymphedema of the arm is the most common and impairing complication after breast cancer surgery with axillary lymph node dissection (ALND). Our prospective study evaluated the effect of two different surgical techniques for ALND on postoperative morbidity. Patients were scheduled to undergo ALND. Patients in group 1 (n = 17) underwent the most common and standard technique of ALND, which uses sharp dissection of the tissue and subsequent electro-coagulation of bleedings. Patients in group 2 (n = 17) underwent a modified standard technique of ALND with clamping and ligatures of all resection margins. Postoperative wound secretion was quantified and patients were followed up for 6 months to assess long-term morbidity. The variations in surgical technique had no significant influence on the outcome variables. However, patients in group 2 showed a tendency to less wound secretion (713 versus 802 mL; P = nonsignificant), a decreased rate of immediate postoperative seromas (11.8 versus 23.5%; P = nonsignificant) and less lymphedema after 3 months (29.4 versus 41.2%; P = nonsignificant). Moreover, the number of resected lymph nodes correlated with the total amount of drained fluid (P = 0.006), the duration of the drain (P = 0.015), and the risk for the development of lymphedema after 3 months (P = 0.016). The described variations in surgical technique had no influence on the outcomes of the patients. The number of resected axillary lymph nodes remains the most important risk factor for treatment-related morbidity. Therefore, a well-balanced choice of the extent of the axillary dissection should be the surgeon's main concern.

Chromosomal abnormalities in fetuses with ultrasonographically detected neural tube defects.

We analyzed the karyotype of fetuses with ultrasonographically detected neural tube defects (NTDs). In our study, we included a total of 194 fetuses with NTDs. We analyzed the type of NTD, the karyotype, maternal age, fetal gestational age at diagnosis, and fetal sex. Of the 194 fetuses with NTDs, 87 were anencephalic and 107 had other, nonanencephalic, NTDs. A total of 12 fetuses were shown to have chromosomal abnormalities. Three of 87 anencephalic fetuses (3.45%) had chromosomal abnormalities. The sex ratio for anencephalic fetuses was 65.5% : 34.5% for female and male fetuses. Nine of 107 fetuses with other NTDs (8.41%) had chromosomal abnormalities. Seven fetuses had isolated NTDs and a further seven fetuses had additional ultrasonographic anomalies. Two of the latter had abnormal karyotypes. The sex ratio of all other NTD cases was 67.3% : 32.7% for female and male fetuses. The high number of chromosomal abnormalities justifies prenatal karyotyping in all fetuses with ultrasonographically diagnosed NTDs.

A peptide epitope derived from the cancer testis antigen HOM-MEL-40/SSX2 capable of inducing CD4⁺ and CD8⁺ T-cell as well as B-cell responses.

BACKGROUND: Antigen-derived HLA class I-restricted peptides can generate specific CD8(+) T-cell responses in vivo and are therefore often used as vaccines for patients with cancer. However, only occasional objective clinical responses have been reported suggesting the necessity of CD4(+) T-cell help and possibly antibodies for the induction of an effective anti-tumor immunity in vivo. The SSX2 gene encodes the cancer testis antigen (CTA) HOM-MEL-40/SSX2, which is frequently expressed in a wide spectrum of cancers. Both humoral and cellular immune responses against SSX2 have been described making SSX2 an attractive candidate for vaccine trials. METHODS: SYFPEITHI algorithm was used to predict five pentadecamer peptides with a high binding probability for six selected HLA-DRB1 subtypes (*0101, *0301, *0401, *0701, *1101, *1501) which are prevalent in the Caucasian population. RESULTS: Using peripheral blood cells of 13 cancer patients and 5 healthy controls, the HOM-MEL-40/SSX2-derived peptide p101-111 was identified as an epitope with dual immunogenicity for both CD4(+) helper and cytotoxic CD8(+) T cells. This epitope also reacted with anti-SSX2 antibodies in the serum of a patient with breast cancer. Most remarkably, SSX2/p101-111 simultaneously induced specific CD8, CD4, and antibody responses in vitro. CONCLUSIONS: p101-111 is the first CTA-derived peptide which induces CD4(+), CD8(+), and B-cell responses in vitro. This triple-immunogenic peptide represents an attractive vaccine candidate for the induction of effective anti-tumor immunity.

The rationale behind collecting umbilical cord blood.

Umbilical cord blood (UCB) is an increasingly important and rich source of stem cells. These cells can be used for the treatment of many diseases, including cancers and immune and genetic disorders. For patients for whom no suitable related donor is available, this source of hematopoietic stem cells offers substantial advantages, notably the relative ease of procurement, the absence of risk to the donor, the small likelihood of transmitting clinically important infections, the low risk of severe graft-versus-host disease (GVHD) and the rapid availability of placental blood for transplantation centers. Even though almost 80 diseases are treatable with cord blood stem cells, 97 percent of cord blood is still disposed of after birth and lost for patients in need! To improve availability of stem cells to a broader community, efforts should be undertaken to collect cord blood and expectant parents should be properly informed of their options with regard to cord blood banking.

A multicenter, prospective, randomized, double-blind, placebo-controlled study to investigate the efficacy of a continuous-combined hormone therapy preparation containing 1mg estradiol valerate/2mg dienogest on hot flushes in postmenopausal women.

OBJECTIVES: To evaluate the effects of an estrogen-reduced, continuous-combined hormone therapy preparation (HT) containing 1mg estradiol valerate (1EV) and 2mg dienogest (2DNG) on the number of moderate and severe hot flushes. METHODS: This study compared the effects of an oral continuous-combined HT containing 1mg EV and 2mg DNG (1EV/2DNG) with those of placebo. The planned treatment duration was 12 weeks. Data were obtained from 324 postmenopausal women. The primary efficacy variable was the individual relative change of the mean number of moderate and severe hot flushes per week. Weeks 5-12 of treatment were compared with the 2 weeks preceding the treatment phase. RESULTS: Moderate and severe hot flushes were reduced by 80.8+/-30.9% in the 1EV/2DNG group and by 41.5+/-39.4% in the placebo group. This difference was statistically significant (p<0.0001; Wilcoxon's rank sum test). The incidence of all types of hot flushes (mild+moderate+severe) was reduced by 75.2+/-30.2% under 1EV/2DNG and by 35.3+/-37.0% under placebo. In the subset of non-hysterectomized women, exposure to 1EV/2DNG led to 2.4+/-6.2 days with bleeding in the reference period of 84 days of treatment, versus 0.3+/-1.3 days in the placebo group. The safety profile of 1EV/2DNG was very similar to that of placebo. CONCLUSIONS: Continuous-combined HT preparation with 1mg EV and 2mg DNG induced a significant reduction of moderate and severe hot flushes compared to placebo (p<0.0001). Thus, this low-estrogen preparation is an effective and safe option for HT.

Prospective study on the expression of cancer testis genes and antibody responses in 100 consecutive patients with primary breast cancer.

To determine the expression of cancer testis (CT) genes and antibody responses in a nonselected population of patients with primary breast cancer, we investigated the composite expression of 11 CT genes by RT-PCR in fresh biopsies of 100 consecutive cases of primary breast carcinoma and by immunohistology in selected RT-PCR-positive cases. Antibody responses against 7 CT antigens were analyzed using recombinant antigen expression on yeast surface. In 98 evaluable cases, SCP-1 and SSX-4 were expressed most frequently (both 65%), followed by HOM-TES-85/CT-8 (47%), GAGE (26%), SSX-1 (20%), NY-ESO-1 (13%), MAGE-3 (11%), SSX-2 (8%), CT-10 (7%), MAGE-4 (4%) and CT-7 (1%). One CT gene was expressed by 90% of the cases; 79% expressed > or =2, 48% > or =3, 29% > or =4, 12% > or =5, 6% > or =6, 3% > or =7, 2% > or =8 and one case coexpressed 9 antigens. Of 100 serum samples screened for CT antigen-specific antibodies, antibodies against NY-ESO-1 were detected in 4 patients, against SCP-1 in 6 patients and against SSX-2 in 1 patient, while no antibodies were detected against MAGE-3, CT-7 and CT-10. Expression of CT genes or antibody responses was not correlated with clinical parameters (menopausal status, tumor size, nodal involvement, grading, histology and estrogen receptor status) or the demonstration of CT gene expression at the protein level, by immunohistology. Our results show that breast carcinomas are among the tumors with the most frequent expression of CT antigens, rendering many patients potential candidates for vaccine trials.

Identification of an HLA-DR-restricted peptide epitope with a promiscuous binding pattern derived from the cancer testis antigen HOM-MEL-40/SSX2.

The SSX2 gene encodes the tumor-specific antigen HOM-MEL-40/SSX2 expressed in a broad spectrum of tumors of different origin, against which humoral and CD8+ T-cell-mediated MHC-I-restricted responses have been demonstrated. Searching for promiscuous MHC-II-restricted peptides that might be suitable as a CD4+ stimulating vaccine for many patients, we used the SYFPEITHI algorithm and identified a HOM-MEL-40/SSX2-derived pentadecamer epitope (p45-59) that induced specific CD4+ T-cell responses restricted by the HLA-DRB1 subtypes *0701, *1101 and *1302 that have a cumulative prevalence of approximately 25% in the Caucasian population. The CD4+-mediated response against p45-59 and its DR restriction was demonstrated by inhibition with anti-CD4 and HLA-DR antibodies, respectively, and by blocking experiments using HLA-specific antibodies. The natural processing and presentation of p45-59 was demonstrated by recognition of the SSX2+ melanoma cell line Me 275 as well as autologous and allogeneic dendritic cells pulsed with whole-protein SSX2 by T cells with specificity for p45-59. p45-59 was able to induce responses in 3/6 breast cancer patients and 1/5 healthy controls. No correlation was found between CD4+ T-cell responses against p45-59 reactivity and anti-SSX2 antibody titers in the serum of patients, suggesting that CD4+ and B-cell responses are regulated independently. p45-59 holds promise as a broadly applicable peptide vaccine for patients with SSX2-positive neoplasms.

Meckel Gruber syndrome: a first trimester diagnosis of a recurrent case.

We report of a case of Meckel Gruber Syndrome (MGS) in a woman, who suffered previously from a pregnancy with the same disorder. MGS, consisting of an occipital encephalocele, bilateral cystic kidneys and postaxial polydactyly, is a rare autosomal recessive disorder, with a recurrence risk of 25%. With the present technology, a targeted ultrasound in the late embryonic or early fetal stages of pregnancy has the potential to diagnose this syndrome. Clinical screening in further pregnancies is of utmost importance and the management of such cases is presented.