Klaus Mayerhofer

Vascular endothelial growth factor (VEGF) in human breast cancer : Correlation with disease-free survival

Studies have shown that microvessel density influences breast‐cancer prognosis. Since tumor angiogenesis is considered to be substantially affected by the excretion of vascular endothelial growth factor (VEGF) from tumor cells, we examined whether VEGF concentration is different in malignant and in non‐malignant breast tissue. It was also of interest to discover whether intratumoral VEGF concentration influences disease‐free survival (DFS) of breast‐cancer patients. Analysis is based on 120 tissue specimens taken from breast fibromas (n = 23), normal epithelial breast tissue adjacent to fibromas (n = 8) and invasive breast cancer (n = 89). VEGF concentration was quantified by using an immunoassay. Microvessel density was determined by immunostaining for factor‐VIII‐related antigen. Median VEGF concentration is given in pg/mg protein (25%‐quantile—75%‐quantile) and it was 0 (0–1.8) in normal breast tissue, 9.8 (0.52–43.0) in fibromas and 130.4 (50.8–362.2) in invasive carcinomas. A univariate Cox model revealed that node status, tumor size, estrogen‐receptor concentration, histological grading and microvessel density were prognostic factors for disease‐free survival in breast cancer. We found a significant correlation between VEGF concentration and microvessel count, but VEGF concentration did not significantly influence disease‐free survival. Although VEGF protein was found at a significantly higher concentration in malignant than in non‐malignant tissue, determination of intratumoral VEGF protein by an enzyme immunoassay was not prognostically relevant in our patient population. Int. J. Cancer 74:455–458, 1997.

Serum soluble Fas levels in ovarian cancer.

Objective To determine the value of serum soluble Fas levels as a prognostic marker for survival of women with ovarian cancer and as a discriminator between benign and malignant adnexal masses. Methods Serum soluble Fas levels were measured with an enzyme-linked immunosorbent assay in 52 women with ovarian cancer, 30 women with benign ovarian cysts, and 35 healthy women. Results Median serum soluble Fas levels in women with ovarian cancer, women with benign ovarian cysts, and healthy women were 3.7 (range 1.6–14.5), 2.3 (range 1.3–4.1), and 1.5 ng/mL (range 0.1–5.6), respectively (P < .001). A univariate logistic regression model showed a significant influence of serum soluble Fas and CA 125 levels on the odds of presenting with ovarian cancer versus benign cysts (P < .001 and P = .001, respectively). In a multivariable logistic regression model for soluble Fas and CA 125, both markers showed a statistically significant influence on the odds of presenting with ovarian cancer versus benign cysts (P = .01 and P = .01, respectively). Increased pretreatment serum soluble Fas levels were associated with shortened disease-free and overall survival (P = .002 and P = .001, respectively). A multivariable Cox regression model identified serum soluble Fas levels as a significant prognostic factor for disease-free and overall survival, independent of tumor stage (P = .04 and P = .03, respectively). Conclusion Soluble Fas levels might be useful as a discriminator between benign ovarian cysts and ovarian cancer, adding to the information obtained with the use of the established tumor marker CA 125. Pretreatment serum soluble Fas levels also might be an independent prognostic factor for disease-free and overall survival.

KI-67 EXPRESSION IN PATIENTS WITH UTERINE LEIOMYOMAS, UTERINE SMOOTH MUSCLE TUMORS OF UNCERTAIN MALIGNANT POTENTIAL (STUMP) AND UTERINE LEIOMYOSARCOMAS (LMS)

Background:  The aim of the current study was to evaluate the expression of Ki‐67 in uterine smooth muscle tumors, comparing leiomyomas, uterine smooth muscle tumors of uncertain malignant potential (STUMP) and uterine leiomyosarcomas (LMS) and to prove the accuracy of a Ki‐67 expression as a useful parameter in the diagnosis of LMS.

Tumor Anemia and Thrombocytosis in Patients with Vulvar Cancer

The aim of our study was to determine the prevalence of tumor anemia and thrombocytosis in patients with vulvar cancer, and to evaluate the prognostic value or pretreatment hemoglobin (Hb) and platelet count regarding disease-free and overall survival of patients with vulvar cancer. We measured pretreatment Hb and platelet count in 62 patients with squamous cell vulvar cancer. The results were correlated to clinical data. Median Hb and platelet count in patients with vulvar cancer were 13.1 g/dl (range 8.3–16.2) and 268,500/μl (range 88,000–778,000), respectively. Cut-off levels of 12 g/dl and 300,000/μl were selected for tumor anemia and tumor thrombocytosis, respectively according to published criteria. Tumor anemia and tumor thrombocytosis were present in 30.6 and 27.4% of patients with vulvar cancer, respectively. In a univariate analysis tumor stage and tumor thrombocytosis were significantly associated with a shortened disease-free (log-rank test, p < 0.001 and p = 0.003, respectively) and overall survival (log-rank test, p < 0.001 and p < 0.001, respectively). Tumor anemia was not associated with a shortened disease-free, but with a shortened overall survival of patients with vulvar cancer (log-rank test, p = 0.1 and p = 0.002, respectively). A multivariate Cox regression model considering tumor stage, tumor anemia, and tumor thrombocytosis showed, however, that pretreatment Hb and platelet count did not confer additional prognostic information to that already obtained by the established prognosticator tumor stage on disease free (multivariate Cox regression model, p = 0.8, p = 0.2, and p = 0.003, respectively) and overall survival (multivariate Cox regression model, p = 0.4, p = 0.5, and p = 0.04, respectively). Pretreatment tumor anemia and tumor thrombocytosis were associated with a poor prognosis, but were not an independent predictor of outcome in patients with vulvar cancer.

Influence of Acupuncture on Duration of Labor

The aim of this case control study was to evaluate the thus far controversially discussed influence of acupuncture (AP) on the duration of labor. Fifty-seven women with AP treatment (group A) were included in our study after spontaneous vaginal full-term delivery. The control group included 63 women (group B). Median duration of the first stage of labor was 196 min in group A and 321 min in group B (Wilcoxon 2-sample test, p < 0.0001). Median duration of the second stage of labor was 57 min in group A and 57 min in group B (Wilcoxon 2-sample test, p = 0.82). Thirty women had a premature rupture of the membranes (PROM), in group A 66.7% and in group B 33.3% (χ2 test, p = 0.02). Women without AP (group B) received significantly more often oxytocin during the first stage of labor compared with group A women (85 and 15%, respectively, χ2 test, p = 0.01) as well as during the second stage of labor (72 and 28%, respectively, χ2 test, p = 0.03). Our study suggests that AP treatment is a recommendable form of childbirth preparation due to its positive effect on the duration of labor, namely by shortening the first stage of labor.

Women’s position during labour: influence on maternal and neonatal outcome

ZusammenfassungHintergrundZiel dieser Arbeit war es, den Einfluss einer aufrechten Geburtsposition im Vergleich zur Rückenlage auf mütterliche, perineale und kindliche Faktoren zu untersuchen.MethodikDiese Fall-Kontroll-Studie wurde an der Abteilung für Geburtshilfe und Gynäkologie der Universitäts-Frauenklinik Wien zwischen 1997 und 2002 durchgeführt. Insgesamt wurden 307 Frauen mit einer aufrechten Geburtsposition inkludiert, wobei als aufrechte oder auch alternative Geburtsposition die Hockgeburt definiert wurde. Die Kontrollgruppe bestand aus 307 paritätsgleichen Frauen mit spontaner vaginaler Geburt in Rückenlage. Unsere Analyse beschränkte sich auf Frauen mit einem Gestationsalter über der 37. Schwangerschaftswoche und einem normal großen Kind in Schädellage. Frauen mit medizinischen oder geburtshilflichen Risikofaktoren wurden von der Studie ausgeschlossen.ErgebnisseEs zeigte sich bei Frauen mit aufrechter Geburtsposition eine statistisch signifikante Abnahme des Schmerzmittel- und Oxytocingebrauchs (p=0,0001; p=0,001). Sowohl die Dauer der Eröffnungsphase als auch die Austreibungsphase zeigte keinen signifikanten Unterschied zwischen beiden Gruppen (p>0,05). Eine statistisch signifikant niedrigere Rate an Episiotomie wurde bei Frauen mit aufrechter Geburtsposition beobachtet (p=0,0001). Die Häufigkeit von Dammverletzungen, Vaginal- und Labialrissen unterschied sich jedoch nicht signifikant zwischen den beiden Gruppen (p>0,05). Auch bezüglich des mütterlichen Blutverlustes konnte kein Unterschied festgestellt werden (p>0,05). Weiters konnten wir keinen Unterschied bezüglich des 1- und 5-Minuten-APGAR-Wertes und des Nabelschnur-pH-Wertes entdecken (p>0,05).SchlussfolgerungDie Ergebnisse dieser Arbeit zeigen, dass die aufrechte Geburtsposition Vorteile wie eine niedrigere Episiotomierate, einen geringeren Schmerzmittel- und Oxytocingebrauch aufweist. Die beste Empfehlung wäre somit, jede Patientin mit niedrigem geburtshilflichen Risiko in der Geburtsposition entbinden zu lassen, die für sie die bequemste darstellt.SummaryAimTo assess the maternal, perineal and neonatal outcomes of an upright position compared with a supine position during vaginal delivery, in terms of defined outcome variables.MethodsThis case-control study was carried out at the Department of Obstetrics and Gynaecology of the University Hospital Vienna between 1997 and 2002. A total of 307 women who delivered in an upright position were enrolled in the study. Upright position was defined as free squatting and was also described as an alternative birth position. 307 controls, delivering in a supine position, were selected from the delivery database as the next parity-matched normal spontaneous vaginal delivery. Our analysis was restricted to a sample of women with a gestational age >37 weeks, a normal sized fetus and a pregnancy with cephalic presentation. Women with medical or obstetric risk factors were excluded.ResultsA statistically significant decrease for the use of medical analgesia (p=0.0001) and oxytocin (p=0.001) was observed in women using the upright birth position. The length of the first and second stages of labour did not significantly differ between the two groups (p>0.05). A significantly lower rate of episiotomy was detected in women who delivered in an upright position compared with women delivering supine (p=0.0001). The frequency of perineal tears, and vaginal and labial trauma did not differ between the two groups (p>0.05). When analysing maternal blood loss, no significant differences between the two groups were found (p>0.05). No differences in APGAR score <7 at 1 and 5 minutes or cord pH<7.1 were observed (p>0.05).ConclusionsThe data indicate that labouring and delivering in an upright position is associated with beneficial effects such as a lower rate of episiotomy, and a reduced use of medical analgesia and oxytocin. In our opinion, the best recommendation is to give low-risk maternity patients the option of bearing in the mode that is most comfortable for them.

Influence of the birth attendant on maternal and neonatal outcomes during normal vaginal delivery: a comparison between midwife and physician management.

SummaryBackgroundThe purpose of this study was to compare the obstetric outcome of low-risk maternity patients attended by certified midwives with that of low-risk maternity patients attended by obstetricians.Patients and methodsObstetric outcome of 1352 midwife patients was compared with that of 1352 age- and parity-matched physician patients with normal spontaneous vaginal delivery at the Department of Obstetrics and Gynecology of the University Hospital Vienna during the period from January 1997 to July 2002. Our analysis was restricted to a sample of low-risk pregnant women. Women with medical or obstetric risk factors were excluded.ResultsA significant decrease in the use of oxytocin (p=0.0001) was observed in women who selected a midwife as their primary birth attendant compared with women in the physician group. In both groups most women gave birth in a supine position; however, significantly more alternative birth positions were used by midwife patients (p=0.0001). Concerning perineal trauma, a significantly lower rate of episiotomies (p=0.0001) and perineal tears of all degrees (p=0.006) were found in midwife patients. When analyzing severe postpartum hemorrhage and postpartum infections, there were no significant differences between the two groups (p>0.05). Concerning neonatal outcome, there were no significant differences in APGAR score < 7 at 5 minutes (p>0.05).Our data clearly show the ability of certified midwives to successfully provide prenatal care and delivery to lowrisk maternity patients, with neonatal outcomes comparable to those of physician patients. The use of certified midwives supervised by obstetricians may provide the optimum model for perinatal care, particularly for those women who are low-risk maternity patients, leaving physicians free to attend to the high-risk elements of care.

Influence of labor induction on obstetric outcomes in patients with prolonged pregnancy: a comparison between elective labor induction and spontaneous onset of labor beyond term.

SummaryBACKGROUND: Prolonged pregnancy is the most frequent reason for induction of labor. This study aims to determine the effects of labor induction on delivery outcome and to quantify the risks of cesarean delivery associated with labor induction in post-date pregnancies. PATIENTS AND METHODS: This retrospective case-control study included a total of 205 women who reached 42 weeks’ gestation (41 weeks and 3 days) between January 2002 and April 2004 and who were scheduled for induction of labor with vaginal prostaglandins. These cases were matched for age and parity with controls in spontaneous labor beyond 41 weeks’ gestation. Women with any additional medical or obstetric risk factors were excluded from the study. Maternal, neonatal and delivery outcomes were the main variables of interest. RESULTS: During the study period the data of 410 women were available for analysis. Our data revealed that the use of amniotomy (p = 0.02), oxytocin (p = 0.006) and epidural analgesia (p = 0.001) was increased significantly in the induction group compared with the control group of women with spontaneous onset of labor beyond term. The frequency of cesarean delivery and vacuum extraction was also significantly higher in the induction group (p = 0.0001). The Bishop score before induction was an important factor that affected the delivery outcome, resulting in significantly higher rates of cesarean section and vacuum extraction when the score was unfavorable (p = 0.0001). A univariate regression model revealed induction per se (p = 0.0001), primiparity (p = 0.0001), increased maternal age (p = 0.006) and an unfavorable Bishop score (p = 0.0001) as statistically significant risk factors for cesarean section. In a multivariate logistic regression model, primiparity (p = 0.03), increased maternal age (p = 0.02) and an unfavorable Bishop score (p = 0.01) remained independent risk factors for cesarean section. High infant birth weight was also an independent risk factor (p = 0.03). CONCLUSIONS: Our data suggest that women undergoing labor induction because of prolonged pregnancy should be sufficiently informed regarding the risks of a cesarean section or a vacuum extraction. Furthermore, the option of elective cesarean section should be considered, particularly in primiparous women with an unfavorable cervix, higher age, and high estimated infant birth weight.ZusammenfassungHINTERGRUND: Den häufigsten Grund für eine Geburtseinleitung stellt die Terminüberschreitung dar. Ziel dieser Arbeit war es, die Auswirkungen der Geburtseinleitung bei Patientinnen mit Terminüberschreitung auf den Geburtsmodus und auf andere mütterliche und kindliche Faktoren zu untersuchen. METHODIK: Zwischen Jänner 2002 und April 2004 wurden insgesamt 205 Frauen, die aufgrund einer Terminüberschreitung (Termin + 10) mit Prostaglandinen eingeleitet wurden, in diese retrospektive Fall-Kontroll-Studie eingeschlossen. Die Kontrollgruppe bestand aus 205 alters- und paritätsgleichen Frauen, die einen spontanen Wehenbeginn nach der 41 Schwangerschaftswoche hatten. Frauen mit medizinischen oder geburtshilflichen Risikofaktoren wurden von der Studie ausgeschlossen. ERGEBNISSE: Unsere Ergebnisse zeigten in der Einleitungsgruppe eine statistisch signifikant höhere Rate an Amniotomien (p = 0,02), einen erhöhten Oxytocingebrauch (p = 0,006) und eine höhere Rate an Epiduralanalgesie (p = 0,0001). Eine statistisch signifikant höhere Sectiorate und Vakuumrate war bei den eingeleiteten Patientinnen im Vergleich zu Frauen mit spontanem Wehenbeginn und Terminüberschreitung zu verzeichnen (p = 0,0001). Der Zervixbefund (evaluiert durch den Bishop Score) vor der Einleitung hatte einen wichtigen Einfluss auf den Geburtsmodus, wobei bei einem ungünstigem Bishop Score sich eine statistisch signifikant höhere Rate an sekundären Sectiones und Vakuumextraktionen fand (p = 0,0001). In einem univariaten logistischen Regressionsmodell waren die Einleitung per se (p = 0,0001), die Primiparität (p = 0,0001), ein erhöhtes mütterliches Alter (p = 0,006) und ein ungünstiger Bishop Score (p = 0,0001) signifikante Risikofaktoren für eine Entbindung per sectionem. Im multivariaten logistischen Regressionsmodell blieben die Primiparität (p = 0,03), ein erhöhtes mütterliches Alter (p = 0,02) und ein ungünstiger Bishop Score (p = 0,01) unabhängige Risikofaktoren. Zusätzlich zeigte sich, dass ein hohes kindliches Geburtsgewicht (p = 0,03) ebenfalls einen unabhängigen Risikofaktor darstellte. SCHLUSSFOLGERUNG: Die Ergebnisse unserer Studie weisen darauf hin, dass Frauen, die aufgrund einer Terminüberschreitung eingeleitet werden, über das erhöhte Risiko einer sekundären Sectio oder einer vaginal-operativen Entbindungsart informiert werden sollten. Bei erstgebärenden Patientinnen mit unreifem Zervixbefund, einem geschätzten hohen kindlichen Geburtsgewicht sowie erhöhtem mütterlichen Alter sollte auch die Möglichkeit einer elektiven Sectio caesarea in Betracht gezogen werden.

Bcl-2 Receptor Expression in Patients With Uterine Smooth Muscle Tumors: An Immunohistochemical Analysis Comparing Leiomyoma, Uterine Smooth Muscle Tumor of Uncertain Malignant Potential, and Leiomyosarcoma:

Objective: Bcl-2 protein is an apoptosis-inhibiting gene product that prevents the normal course of apoptotic cell death in a variety of cells. Additionally, bcl-2 can promote cell replication by reducing the requirement for growth factors. This protein seems, therefore, to play an important role in the growth of tumors. Our aim was to investigate the different expression of bcl-2 in uterine leiomyomas, smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcomas (LMS). Furthermore, the correlation between bcl-2 expression and various clinicopathologic parameters in leiomyosarcomas was assessed to evaluate its prognostic value. Methods: This study included 26 cases of leiomyoma, 22 cases of STUMP, and 21 cases of LMS of the uterus, Bcl-2 expression was investigated by immunohistochemistry from paraffin-embedded tissue. The immunohistochemical findings were compared and correlated with different clinicopathologic paramters. Clinical information, including follow-up data, was obtained from the database of the Department of Gynecology and Obstetrics. Results: Bcl-2 was present in 12 of 21 LMS, eight of 22 STUMP, and 20 of 25 leiomyomas. Significant differences regarding the frequency of bcl-2 expression and the staining intensity were observed between LMS and leiomyoma as well as between STUMP and leiomyoma (P < .05) but not between LMS and STUMP (P > .05). Regarding the outcome of uterine LMS, patients with bcl-2 positive tumors showed less vascular space involvement and longer overall survival (P < .05). Conclusion: Bcl-2 was expressed more frequently and more strongly in leiomyomas compared with LMS and STUMP. Regarding the outcome of uterine LMS, patients with bcl-2-positive tumors showed less vascular space involvement and longer overall survival. The stronger bcl-2 expression in benign leiomyomas and the better clinical outcome of bcl-2-positive LMS indicate that this protein seems to act as a good prognostic factor. Further studies including larger numbers of patients are necessary to establish bcl-2 as a routine marker for improved prognosis in malignant uterine smooth muscle tumors.

The effect of epidural analgesia on the occurrence of obstetric lacerations and on the neonatal outcome during spontaneous vaginal delivery.

Abstract The aim of this study was to determine if epidural analgesia is associated with increased risk of obstetric lacerations during spontaneous vaginal delivery. Furthermore we assessed the effect of epidural analgesia on maternal and neonatal parameters. This multicenter study consisted of an analysis of data from the delivery databases of the University Hospital of Vienna and the Semmelweis Women’s Hospital Vienna. This study was restricted to a sample that included all women with uncomplicated pregnancy, a gestational age >37th weeks and a pregnancy with cephalic presentation. Epidural analgesia was set during the first stage of labour. Techniques and management styles of epidural analgesia were the same in both hospitals. No statistically significant association was found between epidural analgesia and the occurrence of perineal tears (p=0.83), vaginal (p=0.37) or labial trauma (p=0.11). Furthermore the results demonstrated a statistically significant higher rate of primiparous women using epidural analgesia (p=0.001). A statistically significant prolonged second stage of labour was observed in women undergoing epidural analgesia (p=0.0001). Episiotomy was statistically significant more frequent in women requiring epidural analgesia (p=0.0001). Women who were treated with epidural analgesia were more likely to have labour augmented with oxytocin (p=0.001). No statistically significant differences in neonatal outcomes determined by APGAR score (p=0.84) and cord pH (p=0.23) were observed between the two groups. Women undergoing epidural analgesia demonstrated a prolonged second stage of labour, a higher rate of episiotomy and an increased use of oxytocin to augment labour. Some of these adverse effects might be caused by the higher rate of primiparous women using epidural analgesia. However, epidural analgesia showed no evidence of a detrimental effect on the integrity of the birth-canal in spontaneous vaginal delivery. In our opinion it is a save and effective method of pain relief during labour.